Sitienei, J; Kipruto, H; Mansour, O; Ndisha, M; Hanson, C; Wambu, R; Addona, V
In 2012, the World Health Organization estimated that there were 120,000 new cases and 9500 deaths due to tuberculosis (TB) in Kenya. Almost a quarter of the cases were not detected, and the treatment of 4% of notified cases ended in default. To identify the determinants of anti-tuberculosis treatment default. Data from 2012 and 2013 were retrieved from a national case-based electronic data recording system. A comparison was made between new pulmonary TB patients for whom treatment was interrupted vs. those who successfully completed treatment. A total of 106,824 cases were assessed. Human immunodeficiency virus infection was the single most influential risk factor for default (aOR 2.7). More than 94% of patients received family-based directly observed treatment (DOT) and were more likely to default than patients who received DOT from health care workers (aOR 2.0). Caloric nutritional support was associated with lower default rates (aOR 0.89). Males were more likely to default than females (aOR 1.6). Patients cared for in the private sector were less likely to default than those in the public sector (aOR 0.86). Understanding the factors contributing to default can guide future program improvements and serve as a proxy to understanding the factors that constrain access to care among undetected cases.
Reyes-Guillén, Ivett; Sánchez-Pérez, Héctor Javier; Cruz-Burguete, Jorge; Izaurieta-de Juan, Miren
To analyze the perceptions and interactions of the actors involved in anti-tuberculosis treatment, and to explore their influence in treatment defaulting in Los Altos region of Chiapas, Mexico. From November 2002 to August 2003, in-depth interviews were administered to patients with PTB, patients' family members, institutional physicians, community health coordinators, and traditional medicine practitioners. We found different perceptions about PTB between patients and their families and among health personnel, as well as communication barriers between actors. Defaulting is considered to be mainly due to the treatment's adverse effects. It is necessary to conduct research and interventions in the studied area with the aim of changing perceptions, improving sensitization, quality and suitability of management of patients with PTB in a multicultural context, and promoting collaboration between institutional and traditional medicine.
Kiros, Y. K.; Teklu, T.; Desalegn, F.; Tesfay, M.; Klinkenberg, E.; Mulugeta, A.
Tuberculosis (TB) patients in Mekelle Zone, Tigray Region, in Ethiopia. To investigate adherence to anti-tuberculosis treatment. A cross-sectional study in health facilities providing anti-tuberculosis treatment was conducted. Adherence was measured in three ways: through self-reported missed doses,
Guix Comellas, Eva Maria; Force Sanmartín, Enriqueta; Rozas Quesada, Librada; Noguera Julian, Antoni
Tuberculosis (TB) remains a major cause of morbidity and mortality in many countries. This involves a serious public health problem. Adherence to TB treatment is a cornerstone for the control of this disease. Globally, there are major differences between countries as to the prevalence, incidence and mortality tuberculosis. Spain has a incidence rate higher than that of other countries in their socio-economic background. Treatment is prolonged, with significant side effects. Adherence to treatment is essential to be effective, prevent drug resistance and disease control. Children are more vulnerable to developing the disease than the rest of the population. Several direct and indirect methods measure the adherence to treatment, but none is ideal. Some socio-demographic risk factors that influence on adherence are described (immigration...). In addition, there are another more specific child factors to have been add. The literature reviewed highlights the importance of proper monitoring of patients to increase adherence to TB treatment. The role of the nurse and their interventions are very important.
Background: The aim of this study is to assess anti TB treatment compliance and the factors predictive for poor adherence in Sub-Saharan Africa in the last 10 years. Methods: We searched Medline for articles written in English using the terms: "Patient Compliance"[Mesh] OR "Medication Adherence"[Mesh])) AND ...
Czeizel, A.E.; Rockenbauer, M.; Olsen, J.
OUTCOME MEASURES: Congenital abnormalities in newborn infants and fetuses diagnosed prenatally during the second and third trimesters, and postnatally from birth to the age of one year. RESULTS: Of 38,151 controls, 29 (0.08%) were exposed to anti-tuberculosis drug treatment during pregnancy......OBJECTIVE: To study the human teratogenic potential of isoniazid and other anti-tuberculosis drug treatment during pregnancy. DESIGN AND SETTING: Cases from a large population-based dataset at the Hungarian Case-Control Surveillance of Congenital Abnormalities, and controls from the National Birth...... Registry, between 1980 and 1996. Information on all oral anti-tuberculosis drug treatments during pregnancy was medically recorded. STUDY PARTICIPANTS: Women who had newborns or fetuses with congenital abnormalities (case group), and women who had babies with no congenital abnormality (control group). MAIN...
Full Text Available Anti-tuberculosis drug induced liver injury (ATLI is emerging as a significant threat to tuberculosis control in China, though limited data is available about the burden of ATLI at population level. This study aimed to estimate the incidence of ATLI, to better understand its clinical features, and to evaluate its impact on anti-tuberculosis (TB treatment in China.In a population-based prospective study, we monitored 4,304 TB patients receiving directly observed treatment strategy (DOTS treatment, and found that 106 patients developed ATLI with a cumulative incidence of 2.55% (95% Confidence Interval [CI], 2.04%-3.06%. Nausea, vomiting and anorexia were the top three most frequently observed symptoms. There were 35 (33.02% ATLI patients with no symptoms, including 8 with severe hepatotoxicity. Regarding the prognosis of ATLI, 84 cases (79.25% recovered, 18 (16.98% improved, 2 (1.89% failed to respond to the treatment with continued elevation of serum alanine aminotransferase, and 2 (1.89% died as result of ATLI. Of all the ATLI cases, 74 (69.81% cases changed their anti-TB treatment, including 4 (3.77% cases with medication administration change, 21 (19.81% cases with drugs replacement, 54 (50.94% cases with therapy interruption, and 12 (11.32% cases who discontinued therapy. In terms of treatment outcomes, 53 (51.46% cases had TB cured in time, 48 (46.60% cases had therapy prolonged, and 2 (1.94% cases died. Compared with non-ATLI patients, ATLI patients had a 9.25-fold (95%CI, 5.69-15.05 risk of unsuccessful anti-TB treatment outcomes and a 2.11-fold (95%CI, 1.23-3.60 risk of prolonged intensive treatment phase.ATLI could considerably impact the outcomes of anti-TB treatment. Given the incidence of ATLI and the size of TB population in China, the negative impact is substantial. Therefore, more research and efforts are warranted in order to enhance the diagnosis and the prevention of ATLI.
Yu, S N; Cho, O-H; Park, K-H; Jung, J; Kim, Y K; Lee, J Y; Chong, Y-P; Lee, S-O; Choi, S-H; Kim, Y S; Woo, J H; Kim, S-H
A tertiary referral centre in South Korea. To investigate the incidence, clinical characteristics and outcomes of late paradoxical response (>4 months after the initiation of anti-tuberculosis treatment) during and after anti-tuberculosis treatment in non-human immunodeficiency virus (HIV) infected patients with lymph node tuberculosis (TB). We retrospectively reviewed the medical records of non-HIV-infected patients with lymph node TB between 1997 and 2007, and prospectively enrolled patients with newly diagnosed lymph node TB between 2008 and 2013. Of 467 patients with confirmed and probable lymph node TB, 83 (18%) displayed a paradoxical response: 57 of these (69%) were classified as early and 26 (31%) as late paradoxical response. Patients with late paradoxical response (median 12 months) received more prolonged anti-tuberculosis treatment than those with early (median 9 months, P lymph node enlargement increased progressively from those without any paradoxical response (6%), through those with an early response (12%) to those with a late response (23%). Paradoxical response presents late in about one third of non-HIV-infected patients with lymph node TB who experience a response. Although anti-tuberculosis treatment is commonly prolonged in patients with late paradoxical response, post-treatment lymph node enlargement is more frequent in these patients.
Cansu, Döndü Üsküdar; Özbülbül, Nilgün Işıksalan; Akyol, Gülsüm; Arık, Deniz; Korkmaz, Cengiz
Granulomatosis with polyangiitis (GPA) involves upper and lower respiratory tracts and kidneys. Lung involvement is among the most important organ involvements in GPA. GPA's lung involvement might be confused with other granulomatous conditions with lung involvement. In this report, we presented clinical features of two cases with GPA who had been diagnosed as tuberculosis (TBC) and well treated with anti-tuberculosis (anti-TBC) drugs. However, one of two cases had ear-nose-throat (ENT) manifestations before the diagnosis of TBC and her extrapulmonary findings related with GPA have added to clinical features in the following years. In the second case, the manifestations of GPA appeared after 13 months of anti-TBC treatment. We speculated that lung involvement in these cases may be due to GPA rather than TBC. Our aim was to highlight difficulties in the differential diagnosis between GPA and TBC and suggest the possible beneficial effect of anti-TBC drugs on the lung involvement due to GPA in light of the literature data.
Lin, Fei-Shen; Wu, Mei-Ying; Tu, Wen-Jun; Pan, Hong-Qiu; Zheng, Jian; Shi, Jun-Wei; Fei, Zhong-Ting; Zhang, Rui-Mei; Yan, Wei-Guo; Shang, Ming-Qun; Zheng, Qiang; Wang, Meng-Jie; Zhang, Xia
To investigate the prevalence of and risk factors for leukopenia in tuberculosis patients and the impact of anti-tuberculosis regimens on the occurrence of leukopenia in newly treated tuberculosis patients. A total of 1,904 tuberculosis patients were included in the study. A cross-sectional survey of the prevalence of leukopenia was initially conducted, and then factors influencing leukopenia were identified using Logistic regression analysis. Non-treatment factors influencing peripheral blood leukocyte counts were analyzed using univariate COX proportional hazards models. Covariate analysis was used to assess the independent effect of different anti-tuberculosis regimens on peripheral blood leukocyte counts. Being female, advanced age and longer duration of previous anti-tuberculosis treatment (>6 month) were risk factors for leukopenia in tuberculosis patients, while secondary pulmonary tuberculosis, higher body mass index (BMI: 24-27.9 kg/m(2)), and higher degree of education (senior high school or above) were protective factors. Gender, vegetable consumption, drinking, pulmonary infection, other chronic diseases, and use of antibiotics were significantly associated with the development of leukopenia in patients on anti-tuberculosis treatment. In tuberculosis patients treated with anti-tuberculosis regimens not containing antibiotics, peripheral blood leukocyte levels gradually declined with the prolongation of treatment duration. In tuberculosis patients treated with anti-tuberculosis regimens containing antibiotics, peripheral blood leukocyte levels showed a declining trend. Female patients, patients at advanced age and recurrent tuberculosis patients having longer previous anti-tuberculosis treatment are high-risk populations for leukopenia. Attention should be paid to the influence of vegetable consumption and drinking, co-morbidities and use of antibiotics during anti-tuberculosis treatment.
Full Text Available Abstract Background India has 2.0 million estimated tuberculosis (TB cases per annum with an estimated 280,000 TB-related deaths per year. Understanding when in the course of TB treatment patients die is important for determining the type of intervention to be offered and crucially when this intervention should be given. The objectives of the current study were to determine in a large cohort of TB patients in India:- i treatment outcomes including the number who died while on treatment, ii the month of death and iii characteristics associated with "early" death, occurring in the initial 8 weeks of treatment. Methods This was a retrospective study in 16 selected Designated Microscopy Centres (DMCs in Hyderabad, Krishna and Adilabad districts of Andhra Pradesh, South India. A review was performed of treatment cards and medical records of all TB patients (adults and children registered and placed on standardized anti-tuberculosis treatment from January 2005 to September 2009. Results There were 8,240 TB patients (5183 males of whom 492 (6% were known to have died during treatment. Case-fatality was higher in those previously treated (12% and lower in those with extra-pulmonary TB (2%. There was an even distribution of deaths during anti-tuberculosis treatment, with 28% of all patients dying in the first 8 weeks of treatment. Increasing age and new as compared to recurrent TB disease were significantly associated with "early death". Conclusion In this large cohort of TB patients, deaths occurred with an even frequency throughout anti-TB treatment. Reasons may relate to i the treatment of the disease itself, raising concerns about drug adherence, quality of anti-tuberculosis drugs or the presence of undetected drug resistance and ii co-morbidities, such as HIV/AIDS and diabetes mellitus, which are known to influence mortality. More research in this area from prospective and retrospective studies is needed.
van der Watt, J J; Harrison, T B; Benatar, M; Heckmann, J M
Tuberculosis (TB) is increasing in incidence in certain parts of the world, particularly where there is a co-epidemic of human immunodeficiency virus/acquired immune-deficiency syndrome (HIV/AIDS), and it is associated with a significant degree of morbidity and mortality. One of the most common complications of anti-tuberculosis treatment is the development of a painful isoniazid (INH) associated polyneuropathy (PN), which is preventable with adequate pyridoxine supplementation. As PN is also the most frequent neurological complication associated with HIV infection, subjects who are HIV and TB co-infected may be at increased risk of developing PN. In this review, we explore current knowledge of anti-tuberculosis drug associated PN focusing on INH and its relationship to pyridoxine, as well as the additional impact of antiretroviral treatment and TB-HIV co-infection. It is evident that guidelines established for the prevention and treatment of this problem differ between industrialised and developing countries, and that further research is needed to define the optimum dosing of pyridoxine supplementation in populations where there is a significant burden of TB and HIV.
Hasker, Epco; Khodjikhanov, Maksad; Usarova, Shakhnoz; Asamidinov, Umid; Yuldashova, Umida; van der Werf, Marieke J.; Uzakova, Gulnoz; Veen, Jaap
In Tashkent (Uzbekistan), TB treatment is provided in accordance with the DOTS strategy. Of 1087 pulmonary TB patients started on treatment in 2005, 228 (21%) defaulted. This study investigates who the defaulters in Tashkent are, when they default and why they default. We reviewed the records of 126
Leopold D Tientcheu
Full Text Available Epidemiological differences exist between Mycobacterium africanum (Maf- and Mycobacterium tuberculosis (Mtb-infected patients, but to date, contributing host factors have not been characterised. We analysed clinical outcomes, as well as soluble markers and gene expression profiles in unstimulated, and ESAT6/CFP-10-, whole-Maf- and Mtb-stimulated blood samples of 26 Maf- and 49 Mtb-HIV-negative tuberculosis patients before, and after 2 and 6 months of anti-tuberculosis therapy. Before treatment, both groups had similar clinical parameters, but differed in few cytokines concentration and gene expression profiles. Following treatment the body mass index, skinfold thickness and chest X-ray scores showed greater improvement in the Mtb- compared to Maf-infected patients, after adjusting for age, sex and ethnicity (p = 0.02; 0.04 and 0.007, respectively. In addition, in unstimulated blood, IL-12p70, IL12A and TLR9 were significantly higher in Maf-infected patients, while IL-15, IL-8 and MIP-1α were higher in Mtb-infected patients. Overnight stimulation with ESAT-6/CFP-10 induced significantly higher levels of IFN-γ and TNF-α production, as well as gene expression of CCL4, IL1B and TLR4 in Mtb- compared to Maf-infected patients. Our study confirms differences in clinical features and immune genes expression and concentration of proteins associated with inflammatory processes between Mtb- and Maf-infected patients following anti-tuberculosis treatment These findings have public health implications for treatment regimens, and biomarkers for tuberculosis diagnosis and susceptibility.
Tientcheu, Leopold D.; Haks, Mariëlle C.; Agbla, Schadrac C.; Sutherland, Jayne S.; Adetifa, Ifedayo M.; Donkor, Simon; Quinten, Edwin; Daramy, Mohammed; Antonio, Martin; Kampmann, Beate; Ottenhoff, Tom H. M.; Dockrell, Hazel M.; Ota, Martin O.
Epidemiological differences exist between Mycobacterium africanum (Maf)- and Mycobacterium tuberculosis (Mtb)-infected patients, but to date, contributing host factors have not been characterised. We analysed clinical outcomes, as well as soluble markers and gene expression profiles in unstimulated, and ESAT6/CFP-10-, whole-Maf- and Mtb-stimulated blood samples of 26 Maf- and 49 Mtb-HIV-negative tuberculosis patients before, and after 2 and 6 months of anti-tuberculosis therapy. Before treatment, both groups had similar clinical parameters, but differed in few cytokines concentration and gene expression profiles. Following treatment the body mass index, skinfold thickness and chest X-ray scores showed greater improvement in the Mtb- compared to Maf-infected patients, after adjusting for age, sex and ethnicity (p = 0.02; 0.04 and 0.007, respectively). In addition, in unstimulated blood, IL-12p70, IL12A and TLR9 were significantly higher in Maf-infected patients, while IL-15, IL-8 and MIP-1α were higher in Mtb-infected patients. Overnight stimulation with ESAT-6/CFP-10 induced significantly higher levels of IFN-γ and TNF-α production, as well as gene expression of CCL4, IL1B and TLR4 in Mtb- compared to Maf-infected patients. Our study confirms differences in clinical features and immune genes expression and concentration of proteins associated with inflammatory processes between Mtb- and Maf-infected patients following anti-tuberculosis treatment These findings have public health implications for treatment regimens, and biomarkers for tuberculosis diagnosis and susceptibility. PMID:27192147
Full Text Available Abstract Background In Tashkent (Uzbekistan, TB treatment is provided in accordance with the DOTS strategy. Of 1087 pulmonary TB patients started on treatment in 2005, 228 (21% defaulted. This study investigates who the defaulters in Tashkent are, when they default and why they default. Methods We reviewed the records of 126 defaulters (cases and 132 controls and collected information on time of default, demographic factors, social factors, potential risk factors for default, characteristics of treatment and recorded reasons for default. Results Unemployment, being a pensioner, alcoholism and homelessness were associated with default. Patients defaulted mostly during the intensive phase, while they were hospitalized (61%, or just before they were to start the continuation phase (26%. Reasons for default listed in the records were various, 'Refusal of further treatment' (27% and 'Violation of hospital rules' (18% were most frequently recorded. One third of the recorded defaulters did not really default but continued treatment under 'non-DOTS' conditions. Conclusion Whereas patient factors such as unemployment, being a pensioner, alcoholism and homelessness play a role, there are also system factors that need to be addressed to reduce default. Such system factors include the obligatory admission in TB hospitals and the inadequately organized transition from hospitalized to ambulatory treatment.
Jenkins, H E; Ciobanu, A; Plesca, V; Crudu, V; Galusca, I; Soltan, V; Cohen, T
The Republic of Moldova, in Eastern Europe, has among the highest reported nationwide proportions of tuberculosis (TB) patients with multidrug-resistant tuberculosis (MDR-TB) worldwide. Default has been associated with increased mortality and amplification of drug resistance, and may contribute to the high MDR-TB rates in Moldova. To assess risk factors and timing of default from treatment for non-MDR-TB from 2007 to 2010. A retrospective analysis of routine surveillance data on all non-MDR-TB patients reported. A total of 14.7% of non-MDR-TB patients defaulted from treatment during the study period. Independent risk factors for default included sociodemographic factors, such as homelessness, living alone, less formal education and spending substantial time outside Moldova in the year prior to diagnosis; and health-related factors such as human immunodeficiency virus co-infection, greater lung pathology and increasing TB drug resistance. Anti-tuberculosis treatment is usually initiated within an institutional setting in Moldova, and the default risk was highest in the month following the phase of hospitalized treatment (among civilians) and after leaving prison (among those diagnosed while incarcerated). Targeted interventions to increase treatment adherence for patients at highest risk of default, and improving the continuity of care for patients transitioning from institutional to community care may substantially reduce risk of default.
Full Text Available OBJECTIVE: The aim of this study was to evaluate the role of polymerase chain reaction (PCR in the diagnosis of spinal tuberculosis after 2 weeks of preoperative anti-tuberculosis treatment and to compare PCR to the Löwenstein - Jensen Culture (LJC and histopathological examination (HPE methods. METHODS: Twenty-five patients were included in this study. Sixteen patients were diagnosed and treated for spinal tuberculosis based on clinical and radiological evidence. Nine patients were controls. The LJC method and HPE of the specimen were performed according to hospital protocol. PCR was performed using primer encoding insertion of sequences IS6110 for mycobacterium tuberculosis complex. Clinical findings and radiological features were the gold standard for comparison. RESULTS: PCR results were 15 positive and one negative. The sensitivity and specificity of PCR was 94% and 100% respectively (with 95% confidence interval [CI] 67% to 99% and 63% to 100%, respectively. HPE results showed 13 were positive and 3 negative in the spinal tuberculosis group; for the control group, all were negative. Sensitivity and specificity value of HPE was 82 % and 100% respectively (with 95% confidence interval [CI] 54% to 95% and 63% to 100%, respectively. Use of LJC showed only one was positive and 15 were negative in the spinal tuberculosis group whole all nine in the control group were negative. Sensitivity and specificity value of LJC was 6% and 100% respectively (with 95% confidence interval [CI] 0.3% to 32% and 63% to 100%, respectively. CONCLUSION: Our findings showed that the PCR for Mycobacterium tuberculosis is reliable as a method for diagnosis of spinal tuberculosis, even after of 2 weeks of anti-TB treatment, with an overall sensitivity of 94% and specificity of 100%.
Thatiana Lopes Biá Ventura
Full Text Available Tuberculosis (TB remains a serious public health problem aggravated by the emergence of M. tuberculosis (Mtb strains resistant to multiple drugs (MDR. Delay in TB treatment, common in the MDR-TB cases, can lead to deleterious life-threatening inflammation in susceptible hyper-reactive individuals, encouraging the discovery of new anti-Mtb drugs and the use of adjunctive therapy based on anti-inflammatory interventions. In this study, a series of forty synthetic chalcones was evaluated in vitro for their anti-inflammatory and antimycobacterial properties and in silico for pharmacokinetic parameters. Seven compounds strongly inhibited NO and PGE2 production by LPS-stimulated macrophages through the specific inhibition of iNOS and COX-2 expression, respectively, with compounds 4 and 5 standing out in this respect. Four of the seven most active compounds were able to inhibit production of TNF-α and IL-1β. Chalcones that were not toxic to cultured macrophages were tested for antimycobacterial activity. Eight compounds were able to inhibit growth of the M. bovis BCG and Mtb H37Rv strains in bacterial cultures and in infected macrophages. Four of them, including compounds 4 and 5, were active against a hypervirulent clinical Mtb isolate as well. In silico analysis of ADMET properties showed that the evaluated chalcones displayed satisfactory pharmacokinetic parameters. In conclusion, the obtained data demonstrate that at least two of the studied chalcones, compounds 4 and 5, are promising antimycobacterial and anti-inflammatory agents, especially focusing on an anti-tuberculosis dual treatment approach.
James P. Dalton
Full Text Available Much is known regarding the antibiotic susceptibility of planktonic cultures of Mycobacterium tuberculosis, the bacterium responsible for the lung disease tuberculosis (TB. As planktonically-grown M. tuberculosis are unlikely to be entirely representative of the bacterium during infection, we set out to determine how effective a range of anti-mycobacterial treatments were against M. tuberculosis growing as a biofilm, a bacterial phenotype known to be more resistant to antibiotic treatment. Light levels from bioluminescently-labelled M. tuberculosis H37Rv (strain BSG001 were used as a surrogate for bacterial viability, and were monitored before and after one week of treatment. After treatment, biofilms were disrupted, washed and inoculated into fresh broth and plated onto solid media to rescue any surviving bacteria. We found that in this phenotypic state M. tuberculosis was resistant to the majority of the compounds tested. Minimum inhibitory concentrations (MICs increased by 20-fold to greater than 1,000-fold, underlying the potential of this phenotype to cause significant problems during treatment.
Casals, M.; Caminero, J. A.; García-García, J. M.; Jiménez-Fuentes, M. A.; Medina, J. F.; Millet, J. P.; Ruiz-Manzano, J.; Caylá, J.
Objective To determine the case-fatality rate (CFR) at the end of the intensive phase of tuberculosis (TB) treatment, and factors associated with fatality. Methods TB patients diagnosed between 2006 and 2013 were followed-up during treatment. We computed the CFR at the end of the intensive phase of TB treatment, and the incidence of death per 100 person-days (pd) of follow-up. We performed survival analysis using the Kaplan-Meier method and Cox regression, and calculate hazard ratios (HR) and 95% confidence intervals (CI). Results A total of 5,182 patients were included, of whom 180 (3.5%) died; 87 of these deaths (48.3%) occurred during the intensive phase of treatment, with a CFR of 1.7%. The incidence of death was 0.028/100 pd. The following factors were associated with death during the intensive phase: being >50 years (HR = 36.9;CI:4.8–283.4); being retired (HR = 2.4;CI:1.1–5.1); having visited the emergency department (HR = 3.1;CI:1.2–7.7); HIV infection (HR = 3.4;CI:1.6–7.2); initial standard treatment with 3 drugs (HR = 2.0;CI:1.2–3.3) or non-standard treatments (HR = 2.68;CI:1.36–5.25); comprehension difficulties (HR = 2.8;CI:1.3–6.1); and smear-positive sputum (HR = 2.3-CI:1.0–4.8). Conclusion There is a non-negligible CFR during the intensive phase of TB, whose reduction should be prioritised. The CFR could be a useful indicator for evaluating TB programs. PMID:27487189
Dobler, C C; Korver, S; Batbayar, O; Oyuntsetseg, S; Tsolmon, B; Wright, C; Solongo, B; Marais, B J
Many countries restrict access to directly observed therapy (DOT) for tuberculosis (TB) to government health facilities. More innovative approaches are required to reduce non-adherence, improve patient outcomes and limit the risk of selecting drug-resistant strains. We performed a retrospective cohort study in sputum smear-positive patients treated with community-based DOT (home-based DOT or 'lunch' DOT, whereby DOT is provided with a free daily meal once sputum smear conversion has been documented), and conventional clinic-based DOT in Ulaanbaatar, the capital of Mongolia, in 2010-2011. We compared treatment success using community-based home DOT vs. conventional clinic DOT and describe treatment completion rates using lunch DOT. The overall treatment success among new sputum smear-positive TB patients was 85.1% (1505/1768). Patients receiving community DOT had higher cure rates (294/327, 89.9% vs. 1112/1441, 77.2%; aOR 2.66, 95%CI 1.81-3.90) and higher treatment success (306/327, 93.6% vs. 1199/1441, 83.2%; aOR 2.95, 95%CI 1.85-4.71, P Mongolia. It should now be scaled up to be made available for more patients and in all regions of the country.
Background Successful treatment of tuberculosis (TB) involves taking anti-tuberculosis drugs for at least six months. Poor adherence to treatment means patients remain infectious for longer, are more likely to relapse or succumb to tuberculosis and could result in treatment failure as well as foster emergence of drug resistant tuberculosis. Kenya is among countries with high tuberculosis burden globally. The purpose of this study was to determine the duration tuberculosis patients stay in treatment before defaulting and factors associated with default in Nairobi. Methods A Case-Control study; Cases were those who defaulted from treatment and Controls those who completed treatment course between January 2006 and March 2008. All (945) defaulters and 1033 randomly selected controls from among 5659 patients who completed treatment course in 30 high volume sites were enrolled. Secondary data was collected using a facility questionnaire. From among the enrolled, 120 cases and 154 controls were randomly selected and interviewed to obtain primary data not routinely collected. Data was analyzed using SPSS and Epi Info statistical software. Univariate and multivariate logistic regression analysis to determine association and Kaplan-Meier method to determine probability of staying in treatment over time were applied. Results Of 945 defaulters, 22.7% (215) and 20.4% (193) abandoned treatment within first and second months (intensive phase) of treatment respectively. Among 120 defaulters interviewed, 16.7% (20) attributed their default to ignorance, 12.5% (15) to traveling away from treatment site, 11.7% (14) to feeling better and 10.8% (13) to side-effects. On multivariate analysis, inadequate knowledge on tuberculosis (OR 8.67; 95% CI 1.47-51.3), herbal medication use (OR 5.7; 95% CI 1.37-23.7), low income (OR 5.57, CI 1.07-30.0), alcohol abuse (OR 4.97; 95% CI 1.56-15.9), previous default (OR 2.33; 95% CI 1.16-4.68), co-infection with Human immune-deficient Virus (HIV) (OR 1
Ombeka Victor O
Full Text Available Abstract Background Successful treatment of tuberculosis (TB involves taking anti-tuberculosis drugs for at least six months. Poor adherence to treatment means patients remain infectious for longer, are more likely to relapse or succumb to tuberculosis and could result in treatment failure as well as foster emergence of drug resistant tuberculosis. Kenya is among countries with high tuberculosis burden globally. The purpose of this study was to determine the duration tuberculosis patients stay in treatment before defaulting and factors associated with default in Nairobi. Methods A Case-Control study; Cases were those who defaulted from treatment and Controls those who completed treatment course between January 2006 and March 2008. All (945 defaulters and 1033 randomly selected controls from among 5659 patients who completed treatment course in 30 high volume sites were enrolled. Secondary data was collected using a facility questionnaire. From among the enrolled, 120 cases and 154 controls were randomly selected and interviewed to obtain primary data not routinely collected. Data was analyzed using SPSS and Epi Info statistical software. Univariate and multivariate logistic regression analysis to determine association and Kaplan-Meier method to determine probability of staying in treatment over time were applied. Results Of 945 defaulters, 22.7% (215 and 20.4% (193 abandoned treatment within first and second months (intensive phase of treatment respectively. Among 120 defaulters interviewed, 16.7% (20 attributed their default to ignorance, 12.5% (15 to traveling away from treatment site, 11.7% (14 to feeling better and 10.8% (13 to side-effects. On multivariate analysis, inadequate knowledge on tuberculosis (OR 8.67; 95% CI 1.47-51.3, herbal medication use (OR 5.7; 95% CI 1.37-23.7, low income (OR 5.57, CI 1.07-30.0, alcohol abuse (OR 4.97; 95% CI 1.56-15.9, previous default (OR 2.33; 95% CI 1.16-4.68, co-infection with Human immune
Akilimali, P Z; Tshilumbu, J M K; Mavila, A K; Kaba, D K
The study aimed to determine the clinical forms of tuberculosis and therapeutic outcome of anti-tuberculosis treatment in the context of HIV-tuberculosis co-infection. A retrospective cohort of 120 HIV-positive patients with tuberculosis and 297 HIV-negative patients with tuberculosis attending the Kabinda Center was followed from 2010 to June, 30th 2013. The logistic regression model identified the determinants of a defavorable outcome after initiation of tuberculostatics. The proportion of female patients was higher in the co-infected group compared with the non-co-infected group (60.8% versus 42.7%, P<0.001). HIV-seropositive patients had more forms of pulmonary smear-negative (39.2% versus 25.3%, P<0.002) and extra-pulmonary (38% versus 35%, P<0.002) tuberculosis than HIV-negative patients. HIV-positive serology (OR: 3.13, 95%CI: 1.72-5.69) and age of patients more than 41 years (OR: 3.15, 95%CI: 1.36-7.29) were associated with an unfavorable outcome. This study highlights the usefulness of a systematically determining immunological status in co-infected patients and a timely and systematic ARV treatment, together with early diagnosis of tuberculosis. It also emphasizes the importance of adherence to support measures in order to improve tuberculosis treatment outcomes in co-infected patients. Copyright © 2015 Elsevier Masson SAS. All rights reserved.
Piñeiro Pérez, Roi; Santiago García, Begoña; Fernández Llamazares, Cecilia M; Baquero Artigao, Fernando; Noguera Julian, Antoni; Mellado Peña, María José
There are no paediatric formulations of anti-tuberculous drugs in Spain, with the only exception being rifampicin. Some paediatricians often prescribe composite formulations (CF), while others prefer to give crushed tablets. Nevertheless, there is no consensus in this regard, or any pharmacokinetic studies validating these procedures. In this situation, the Spanish Network for the Study of Paediatric Tuberculosis (pTBred) has launched the Magistral Project, which has as its first phase aims to analyse the desirability of developing child-friendly pharmaceutical formulations and other aspects regarding the anti-tuberculous drug prescription in children. A cross-sectional, multicentre, nationwide study was conducted, based on an online questionnaire sent to members of pTBred between February and March 2015. Fifty-four responses from 67 consulted institutions were received. Most of the respondents reported prescribing crushed tablets. A significant number of those surveyed, although being fewer, prescribe CF, for which availability varies widely among institutions. Eighty-three percent replied that it would be essential to have fixed dose combinations of anti-tuberculous drugs, specifically adapted to paediatric doses and administered by CF or tablets. Among the surveyed institutions, differences were found in the management of latent tuberculosis infection, in the use of directly observed therapy, and in the monitoring of adverse events. Our survey reveals great diversity in anti-tuberculous drug prescription in children, due to the lack of suitable infant formulations, which could have an impact on treatment adherence and outcomes. pTBred intends to develop a pioneering and useful consensus document on the management of anti-tuberculous medication in children. Copyright © 2015 Asociación Española de Pediatría. Published by Elsevier España, S.L.U. All rights reserved.
Among all the defaulters successfully traced, half of them were found dead. Most of the treatment interruption occurred during the second and third moths of ... of treatment interruption in TB patients is highly recommended in the study area. Key words: Tuberculosis ;Treatment interruption (defaulting) ;Awi Zone; Ethiopia.
Pardeshi, Geeta S
Default remains an important challenge for the Revised National Tuberculosis Control Programme, which has achieved improved cure rates. This study describes the pattern of time of default in patients on DOTS. Tuberculosis Unit in District Tuberculosis Centre, Yavatmal, India; Retrospective cohort study. This analysis was done among the cohort of patients of registered at the Tuberculosis Unit during the year 2004. The time of default was assessed from the tuberculosis register. The sputum smear conversion and treatment outcome were also assessed. Kaplan-Meier plots and log rank tests. Overall, the default rate amongst the 716 patients registered at the Tuberculosis Unit was 10.33%. There was a significant difference in the default rate over time between the three DOTS categories (log rank statistic= 15.49, P=0.0004). Amongst the 331 smear-positive patients, the cumulative default rates at the end of intensive phase were 4% and 16%; while by end of treatment period, the default rates were 6% and 31% in category I and category II, respectively. A majority of the smear-positive patients in category II belonged to the group 'treatment after default' (56/95), and 30% of them defaulted during re-treatment. The sputum smear conversion rate at the end of intensive phase was 84%. Amongst 36 patients without smear conversion at the end of intensive phase, 55% had treatment failure. Patients defaulting in intensive phase of treatment and without smear conversion at the end of intensive phase should be retrieved on a priority basis. Default constitutes not only a major reason for patients needing re-treatment but also a risk for repeated default.
Tadele Teshome Woimo
Full Text Available Abstract Background Evidence exists pointing out how non-adherence to treatment remains a major hurdle to efficient tuberculosis control in developing countries. Many tuberculosis (Tb patients do not complete their six-month course of anti-tuberculosis medications and are not aware of the importance of sputum re-examinations, thereby putting themselves at risk of developing multidrug-resistant and extensively drug-resistant forms of tuberculosis and relapse. However, there is a dearth of publications about non-adherence towards anti-Tb medication in these settings. We assessed the prevalence of and associated factors for anti-Tb treatment non-adherence in public health care facilities of South Ethiopia. Methods This was a cross-sectional survey using both quantitative and qualitative methods. The quantitative study was conducted among 261 Tb patients from 17 health centers and one general hospital. The qualitative aspect included an in-depth interview of 14 key informants. For quantitative data, the analysis of descriptive statistics, bivariate and multiple logistic regression was carried out, while thematic framework analysis was applied for the qualitative data. Results The prevalence of non-adherence towards anti-Tb treatment was 24.5%. Multiple logistic regression analysis demonstrated that poor knowledge towards tuberculosis and its treatment (AOR = 4.6, 95%CI: 1.4-15.6, cost of medication other than Tb (AOR = 4.7, 95%CI: 1.7-13.4, having of health information at every visit (AOR = 3, 95% CI: 1.1-8.4 and distance of DOTS center from individual home (AOR = 5.7, 95%CI: 1.9-16.8 showed statistically significant association with non-adherence towards anti- tuberculosis treatment. Qualitative study also revealed that distance, lack of awareness about importance of treatment completion and cost of transportation were the major barriers for adherence. Conclusions A quarter of Tb patients interrupted their treatment due to knowledge
Full Text Available Public tuberculosis (TB clinics in urban Morocco.Explore risk factors for TB treatment default and develop a prediction tool. Assess consequences of default, specifically risk for transmission or development of drug resistance.Case-control study comparing patients who defaulted from TB treatment and patients who completed it using quantitative methods and open-ended questions. Results were interpreted in light of health professionals' perspectives from a parallel study. A predictive model and simple tool to identify patients at high risk of default were developed. Sputum from cases with pulmonary TB was collected for smear and drug susceptibility testing.91 cases and 186 controls enrolled. Independent risk factors for default included current smoking, retreatment, work interference with adherence, daily directly observed therapy, side effects, quick symptom resolution, and not knowing one's treatment duration. Age >50 years, never smoking, and having friends who knew one's diagnosis were protective. A simple scoring tool incorporating these factors was 82.4% sensitive and 87.6% specific for predicting default in this population. Clinicians and patients described additional contributors to default and suggested locally-relevant intervention targets. Among 89 cases with pulmonary TB, 71% had sputum that was smear positive for TB. Drug resistance was rare.The causes of default from TB treatment were explored through synthesis of qualitative and quantitative data from patients and health professionals. A scoring tool with high sensitivity and specificity to predict default was developed. Prospective evaluation of this tool coupled with targeted interventions based on our findings is warranted. Of note, the risk of TB transmission from patients who default treatment to others is likely to be high. The commonly-feared risk of drug resistance, though, may be low; a larger study is required to confirm these findings.
Cherkaoui, Imad; Sabouni, Radia; Ghali, Iraqi; Kizub, Darya; Billioux, Alexander C; Bennani, Kenza; Bourkadi, Jamal Eddine; Benmamoun, Abderrahmane; Lahlou, Ouafae; Aouad, Rajae El; Dooley, Kelly E
Public tuberculosis (TB) clinics in urban Morocco. Explore risk factors for TB treatment default and develop a prediction tool. Assess consequences of default, specifically risk for transmission or development of drug resistance. Case-control study comparing patients who defaulted from TB treatment and patients who completed it using quantitative methods and open-ended questions. Results were interpreted in light of health professionals' perspectives from a parallel study. A predictive model and simple tool to identify patients at high risk of default were developed. Sputum from cases with pulmonary TB was collected for smear and drug susceptibility testing. 91 cases and 186 controls enrolled. Independent risk factors for default included current smoking, retreatment, work interference with adherence, daily directly observed therapy, side effects, quick symptom resolution, and not knowing one's treatment duration. Age >50 years, never smoking, and having friends who knew one's diagnosis were protective. A simple scoring tool incorporating these factors was 82.4% sensitive and 87.6% specific for predicting default in this population. Clinicians and patients described additional contributors to default and suggested locally-relevant intervention targets. Among 89 cases with pulmonary TB, 71% had sputum that was smear positive for TB. Drug resistance was rare. The causes of default from TB treatment were explored through synthesis of qualitative and quantitative data from patients and health professionals. A scoring tool with high sensitivity and specificity to predict default was developed. Prospective evaluation of this tool coupled with targeted interventions based on our findings is warranted. Of note, the risk of TB transmission from patients who default treatment to others is likely to be high. The commonly-feared risk of drug resistance, though, may be low; a larger study is required to confirm these findings.
Ghali, Iraqi; Kizub, Darya; Billioux, Alexander C.; Bennani, Kenza; Bourkadi, Jamal Eddine; Benmamoun, Abderrahmane; Lahlou, Ouafae; Aouad, Rajae El; Dooley, Kelly E.
Setting Public tuberculosis (TB) clinics in urban Morocco. Objective Explore risk factors for TB treatment default and develop a prediction tool. Assess consequences of default, specifically risk for transmission or development of drug resistance. Design Case-control study comparing patients who defaulted from TB treatment and patients who completed it using quantitative methods and open-ended questions. Results were interpreted in light of health professionals’ perspectives from a parallel study. A predictive model and simple tool to identify patients at high risk of default were developed. Sputum from cases with pulmonary TB was collected for smear and drug susceptibility testing. Results 91 cases and 186 controls enrolled. Independent risk factors for default included current smoking, retreatment, work interference with adherence, daily directly observed therapy, side effects, quick symptom resolution, and not knowing one’s treatment duration. Age >50 years, never smoking, and having friends who knew one’s diagnosis were protective. A simple scoring tool incorporating these factors was 82.4% sensitive and 87.6% specific for predicting default in this population. Clinicians and patients described additional contributors to default and suggested locally-relevant intervention targets. Among 89 cases with pulmonary TB, 71% had sputum that was smear positive for TB. Drug resistance was rare. Conclusion The causes of default from TB treatment were explored through synthesis of qualitative and quantitative data from patients and health professionals. A scoring tool with high sensitivity and specificity to predict default was developed. Prospective evaluation of this tool coupled with targeted interventions based on our findings is warranted. Of note, the risk of TB transmission from patients who default treatment to others is likely to be high. The commonly-feared risk of drug resistance, though, may be low; a larger study is required to confirm these findings
For those who were not met at home proxy interviewees such as a neighbour or a family member were asked if they were available. Of the 100 patients who had enrolled in the ART treatment programme during the study period, 36% of the study population defaulted treatment, 18% had died while 46% were alive and well.
Minime-Lingoupou, F; Manirakiza, A; Yango, F; Zandanga, G; Le Faou, A; Rigouts, L
The Central African Republic (CAR) is a country with a high burden of tuberculosis (TB). Although its national tuberculosis programme is effective, there is no continuous surveillance system for anti-tuberculosis drug resistance in place. To establish base-line anti-tuberculosis drug resistance data to allow for future monitoring of trends and evolutions. More specifically, we aimed at investigating primary anti-tuberculosis drugs in Bangui and Bimbo, two cities of CAR. A total of 225 Mycobacterium tuberculosis isolates were tested for susceptibility to the anti-tuberculosis drugs commonly used in the country (isoniazid [INH, H], rifampicin [R], streptomycin [SM, S] and ethambutol [EMB, E]). Human immunodeficiency virus co-infection was recorded. Overall primary drug resistance was found to be 14.7% (33/225). The highest rate of primary resistance was for INH (9.3%), followed by SM (8.4%), and EMB (2.2%). The multidrug resistance rate was 0.4%. Our study indicates that primary drug resistance levels in urban settings of CAR are similar to or lower than in other African cities, and that the spread of multidrug-resistant TB in this population is limited. Extended nationwide monitoring of drug resistance remains important, especially in view of the planned introduction of a new treatment regimen (2HRZE/4HR [Z = pyrazinamide]).
Tang, Ying; Zhao, Meigui; Wang, Yunxia; Gong, Yanhong; Yin, Xiaoxv; Zhao, Angui; Zheng, Juanjuan; Liu, Zhenyang; Jian, Xiaofang; Wang, Wenxin; Wu, Chunmei; Lu, Zuxun
Non-adherence to tuberculosis (TB) treatment threatens the success of treatment, increases the risk of TB spread, and leads to the development of drug resistance. The present study assessed non-adherence to anti-TB treatment among internal migrants with pulmonary TB living in Shenzhen, China, and examined risk factors for non-adherence in order to identify targets for intervention. A total of 794 internal migrants with TB treated at Bao'an Hospital for Chronic Disease Prevention and Cure, Shenzhen, were recruited. Structured questionnaires were used to collect data on these patients' history and experiences with TB treatment. Ordinal logistic regression model were used to identify risk factors for non-adherence. The proportion of patients who had missed one dose of medication within two weeks was 93/794 (11.71%), and those who missed at least two doses of medication within two weeks was 167/794 (21.03%), with a total of 33.74% of patients not adhering to TB treatment. Lack of knowledge about TB treatment and longer travel time to the nearest community health centers are significant predictors for non-adherence. The present study shows that non-adherence is common among internal migrants with TB. Patients who lack knowledge about TB treatment or have to travel far to get treated are prone to miss one or more doses of medication. Interventions to improve health education and healthcare access are essential to reduce non-adherence to TB treatment among internal migrants.
Velayutham, Banu Rekha Vaithilingam; Nair, Dina; Chandrasekaran, Vedachalam; Raman, Balambal; Sekar, Gomathy; Watson, Basilea; Charles, Niruparani; Malaisamy, Muniyandi; Thomas, Aleyamma; Swaminathan, Soumya
The demographic transition in India has resulted in an increase in the elderly population. There is limited data on the profile of elderly tuberculosis (TB) patients and their treatment outcomes in India. To compare the clinical profile, presentation and response to anti-TB treatment among elderly (≥ 60 yrs) and younger (15-59 yrs) TB patients treated under the Revised National TB Control programme. Retrospective cohort analysis of TB patients treated from May 1999 to December 2004 in one Tuberculosis Unit of Tiruvallur district, South India. Records of 865 elderly and 4343 younger TB patients were examined: elderly were more likely to be male (84% vs. 71%), smokers (46% vs.37%), illiterate (63% vs. 45%), identified by active case finding through survey (19% vs. 11%), have pulmonary TB (96% vs. 91%) and initial smear negative disease (46% vs. 36%) compared to younger (for all ptuberculosis susceptibility to first line anti-TB drugs did not differ (elderly 87% vs. younger 84%) (p = 0.20). Side effects related to anti-TB drugs were reported by a higher proportion of elderly patients (63% vs. 54%) (p = 0.005). Previously treated patients had similar treatment outcomes in both the groups. Elderly TB patients are less likely to have smear positive disease. Newly diagnosed elderly TB patients are more likely to be lost to follow-up or die and report drug side effects. Suitable interventions need to be developed for effective management and better treatment outcomes of TB in the elderly.
Ma. de Lourdes García-García
Full Text Available Objetivo. Evaluar la eficacia y la eficiencia del tratamiento antituberculoso administrado por la Secretaría de Salud (SSA en las jurisdicciones sanitarias de Cuernavaca y Cuautla, estado de Morelos, en el periodo 1992-1996. Material y métodos. Se hizo una revisión retrospectiva de las tarjetas de control de tratamiento en pacientes tuberculosos. Se utilizaron las definiciones contenidas en la Norma Oficial para el Control y Prevención de la Tuberculosis en la Atención Primaria a la Salud. La información fue vaciada en formatos estandarizados y se analizó mediante el programa SAS y Epi Info. Se visitaron las 149 unidades de atención primaria y los cuatro hospitales de la zona de estudio. Resultados. Se encontraron las tarjetas correspondientes a 288 pacientes, de los cuales 260 eran de casos nuevos. Estos pacientes recibieron en conjunto 311 tratamientos, de los cuales 85% fueron supervisados. Las tarjetas revisadas correspondieron al 60% de los casos notificados por la SSA en el mismo periodo. El grupo de pacientes tuberculosos tuvo mayor edad que la media poblacional y mayor probabilidad de pertenecer a los estratos socioeconómicos medio y bajo que la población general del área. Se analizaron 246 esquemas de tratamiento y se encontró que 32% presentó curación bacteriológica; 26%, curación probable; 18% abandonó el tratamiento; 1% fracasó en el tratamiento, y 3% murió durante el tratamiento. En 20% de los casos se desconoció el resultado del tratamiento. La frecuencia de curación fue mayor en los casos nuevos (61% que en los retratamientos (38% (pObjective. To evaluate the efficacy and efficiency of tuberculosis treatment administered by the Secretaría de Salud (SSA in the sanitary jurisdictions of Cuernavaca and Cuautla, Morelos, for the 1992-1996 period by retrospectively reviewing tuberculosis treatment control cards. Material and methods. Official Norm for Tuberculosis Prevention and Control in Primary Care Units
Banu Rekha Vaithilingam Velayutham
Full Text Available INTRODUCTION: The demographic transition in India has resulted in an increase in the elderly population. There is limited data on the profile of elderly tuberculosis (TB patients and their treatment outcomes in India. OBJECTIVE: To compare the clinical profile, presentation and response to anti-TB treatment among elderly (≥ 60 yrs and younger (15-59 yrs TB patients treated under the Revised National TB Control programme. METHODOLOGY: Retrospective cohort analysis of TB patients treated from May 1999 to December 2004 in one Tuberculosis Unit of Tiruvallur district, South India. RESULTS: Records of 865 elderly and 4343 younger TB patients were examined: elderly were more likely to be male (84% vs. 71%, smokers (46% vs.37%, illiterate (63% vs. 45%, identified by active case finding through survey (19% vs. 11%, have pulmonary TB (96% vs. 91% and initial smear negative disease (46% vs. 36% compared to younger (for all p<0.001. Among a total of 352 elderly and 1933 younger new smear positive pulmonary TB, the elderly had higher loss to follow-up (15% vs. 11%; p = 0.03 and death rates (9% vs. 4%; p<0.001. Mycobacterium tuberculosis susceptibility to first line anti-TB drugs did not differ (elderly 87% vs. younger 84% (p = 0.20. Side effects related to anti-TB drugs were reported by a higher proportion of elderly patients (63% vs. 54% (p = 0.005. Previously treated patients had similar treatment outcomes in both the groups. CONCLUSION: Elderly TB patients are less likely to have smear positive disease. Newly diagnosed elderly TB patients are more likely to be lost to follow-up or die and report drug side effects. Suitable interventions need to be developed for effective management and better treatment outcomes of TB in the elderly.
Park, Cheol-Kyu; Shin, Hong-Joon; Kim, Yu-Il; Lim, Sung-Chul; Yoon, Jeong-Sun; Kim, Young-Su; Kim, Jung-Chul; Kwon, Yong-Soo
Default from tuberculosis (TB) treatment could exacerbate the disease and result in the emergence of drug resistance. This study identified the risk factors for default from TB treatment in Korea. This single-center case-control study analyzed 46 default cases and 100 controls. Default was defined as interrupting treatment for 2 or more consecutive months. The reasons for default were mainly incorrect perception or information about TB (41.3%) and experience of adverse events due to TB drugs (41.3%). In univariate analysis, low income (defaulter (15.2% vs. 2.0%, P = 0.005), and combined extrapulmonary TB (54.3% vs. 34.0%, P = 0.020) were significant risk factors for default. In multivariate analysis, the absence of TB stigma (adjusted odd ratio [aOR]: 46.299, 95% confidence interval [CI]: 8.078-265.365, P defaulters (aOR: 33.226, 95% CI: 2.658-415.309, P = 0.007), and low income (aOR: 5.246, 95% CI: 1.249-22.029, P = 0.024) were independent predictors of default from TB treatment. In conclusion, patients with absence of disease stigma, treated by a non-pulmonologist, who were former defaulters, and with low income should be carefully monitored during TB treatment in Korea to avoid treatment default.
Default from tuberculosis (TB) treatment could exacerbate the disease and result in the emergence of drug resistance. This study identified the risk factors for default from TB treatment in Korea. This single-center case–control study analyzed 46 default cases and 100 controls. Default was defined as interrupting treatment for 2 or more consecutive months. The reasons for default were mainly incorrect perception or information about TB (41.3%) and experience of adverse events due to TB drugs (41.3%). In univariate analysis, low income (defaulter (15.2% vs. 2.0%, P = 0.005), and combined extrapulmonary TB (54.3% vs. 34.0%, P = 0.020) were significant risk factors for default. In multivariate analysis, the absence of TB stigma (adjusted odd ratio [aOR]: 46.299, 95% confidence interval [CI]: 8.078–265.365, P defaulters (aOR: 33.226, 95% CI: 2.658–415.309, P = 0.007), and low income (aOR: 5.246, 95% CI: 1.249–22.029, P = 0.024) were independent predictors of default from TB treatment. In conclusion, patients with absence of disease stigma, treated by a non-pulmonologist, who were former defaulters, and with low income should be carefully monitored during TB treatment in Korea to avoid treatment default. PMID:26839480
N. V. Zolotova
Full Text Available Specific features of psychological state were studied in 295 pulmonary tuberculosis patients with satisfactory tolerance to anti-tuberculosis medications and 75 patients poorly tolerating the treatment.Before the treatment start the patients who later demonstrated adverse reactions to treatment were diagnosed with more intense neurotic and hypochondriac personal features, destructive reactions and higher level of emotional tension and frustration – all the above promote dysregulation of the host adaptation. The research demonstrated the need to consider psychological aspects when studying the tolerance to anti-tuberculosis chemotherapy.
Cara S Kosack
Full Text Available BACKGROUND: Thyroid-stimulating hormone (TSH promotes expression of thyroid hormones which are essential for metabolism, growth, and development. Second-line drugs to treat tuberculosis (TB can cause hypothyroidism by suppressing thyroid hormone synthesis. Therefore, TSH levels are routinely measured in TB patients receiving second-line drugs, and thyroxin treatment is initiated where indicated. However, standard TSH tests are technically demanding for many low-resource settings where TB is prevalent; a simple and inexpensive test is urgently needed. METHODS: As a proof of concept study TSH was measured in routinely collected sera at the University Medical Center Utrecht, Netherlands, using the TSH-CHECK-1 (VEDALAB, Alençon, France, a lateral-flow rapid immunochromatographic assay with a TSH cut-off value of 10 µIU/mL, the standard threshold for initiating treatment. These results were compared with TSH levels measured by a reference standard (UniCel DXi 800 imunoassay system, Beckman Coulter, USA. Sensitivity, specificity, and likelihood ratios were then calculated. RESULTS: A total of 215 serum samples were evaluated: 107 with TSH values <10 µIU/mL and 108 with values ≥10 µIU/mL. TSH-CHECK-1 test sensitivity was found to be 100.0% (95% CI: 96.6-100.0 and specificity was 76.6% (95% CI: 67.5-84.3. Predictive values (PV were modelled for different levels of prevalence. For a prevalence of 10% and 50%, the positive PV was 32.2% (95% CI: 25.0-39.7% and 81.1% (95% CI: 75.0-85.5%, respectively; the negative PV was 100% (95% CI: 98.9-100% and 100% (95% CI: 91.3-100% respectively. DISCUSSION/CONCLUSIONS: The TSH-CHECK-1 rapid test was practical and simple to perform but difficult to interpret on weak positive results. All sera with TSH≥10 µIU/mL were correctly identified, but the test lacked sufficient specificity. Given its excellent negative PV in this evaluation, the test shows promise for ruling out hypothyroidism. However, so far it
Full Text Available El objetivo del presente estudio fue analizar el impacto epidemiológico producido por la aplicación de la estrategia del tratamiento para tuberculosis (TB de corta duración y directamente observado (DOTS, y su correlación con el éxito en la Región Sanitaria V, durante el año 2003. Se evaluó la curación comparando dos grupos de estudio. Grupo 1: municipios con 65% o más de los casos con DOTS, y Grupo 2: con 64% o menos de los pacientes bajo esta estrategia o sin su aplicación. Se analizó la letalidad global y de pacientes HIV (+ en ambos grupos. En el grupo 1 el éxito del tratamiento fue 85.7%, con curación en las formas pulmonares confirmadas de 86.2% y abandono de 8.8%. En el grupo 2 la curación alcanzó el 67.6%, en pulmonares confirmados 68.1% y el abandono de 21.8%. La letalidad global fue 5.2%, en pacientes HIV (+ 22.3% y en los HIV (- 4.1%. La curación en TB/HIV en el grupo 1 fue 55.2%, con abandono de 6.9%; en el grupo 2 curó el 46.4% y abandonó el 19.7%. El 31.0% de pacientes HIV (+ fallecieron en el grupo 1 y 16.1% en el grupo 2. La implementación del DOTS, permitió alcanzar la meta de curar el 85% de los casos, probando ser una herramienta eficaz, capaz de garantizar la curación de la mayoría de los pacientes y reducir el riesgo de enfermar de la comunidad.The aim of this study was to analyze the epidemiologic impact produced by Direct Observed Treatment Strategy (DOTS application regarding to its success in the 5th Sanitary Region during the year 2 003. The cure was evaluated by a cohort study comparing two groups. Group 1: Districts in which DOTS were applied in 65% or more TB patients; group 2: Districts applying DOTS in 64% or less, or without its implementation. The global mortality was analyzed on HIV (- as well as on HIV (+ patients in both groups. In Municipalities where DOTS strategy was applied in >65% of notified cases, the treatment success was 85.7%; the cure rate of bacteriological confirmed
Full Text Available Plant derived isoprenoids commonly called terpenoids, are not only useful as chemosytemic markers but are increasingly attracting attention in the development of newer drugs for the treatment of multi-drug resistant tuberculosis. Anti-tuberculosis activity guided solvent fractionation and chromatographic separation of the chloroform extract of S. guineense stem bark resulted in the isolation of two bioactive 3-β-hydroxylupane-type isoprenoids: betulinic acid methylenediol ester (1 (MIC; 0.15 mg/mL and betulinic acid (2 (MIC; 0.60 mg/mL. The structures of the isolated compounds were elucidated using spectroscopic techniques. The antituberculosis assay was done using the Mycobacterium Growth Indicator Tube (MGIT method. This is the first report of the isolation of the anti-tuberculosis constituents of S. guineense and its potentials for the development of drug leads for the treatment of tuberculosis thus validating its ethno-medicinal uses.
Full Text Available and Nanotechnology- based Approaches for Active Targeted Delivery of Anti-Tuberculosis Drugs Presented by : Bathabile Ramalapa CSIR Emerging Researcher Symposium 10 0ctober 2012 Outline ? Background: Challenges in the current TB treatment ? Proposed Solution...-expressed by TB infected macrophages Aptamers: RNA/DNA that bind to a specific target molecule ?Enhance drug efficiency at site of infection ?Reduce systemic toxicity Aptamer Synthesis: SELEX Method ? CSIR 2012 www.csir.co.za Partitioning...
Conclusions: Salient factors influence TB patient treatment default in the Free State Province. Therefore, the strengthening of clinical and programmatic interventions for patients at high risk of treatment default is recommended. In particular, ART provision to co-infected cases facilitates TB treatment adherence and outcomes.
Kabedi, M J; Kashongwe, M; Kayembe, J M; Mumba Ngoyi, D; Mampasi, P; Mbaya, P; Fissette, K; Verhaegen, J; Portaels, F; Muyembe-Tamfum, J J
In a descriptive cross-sectional study carried out in Kinshasa between July 2003 and January 2004, we determined the prevalence of the primary resistance of M. tuberculosis to first-line anti-tuberculosis drugs. The antibiogram was performed with the proportion method on 301 isolats from patients who all had a first episode of pulmonary tuberculosis with positive microscopy (TPM+) and who had not received any anti-tuberculosis treatment before. The primary resistance rate reached 43.5%; it reached 31.6% in 1990. The multi-drug-resistance rate (MDR-TB) notified as resistant to both rifamicine and isoniazide rose to 5.3%. This rate of primary resistance is among the highest in Africa. The emergence of the resistant strains and specially the multi-drug-resistant strains (MDR-TB) in Kinshasa requires a regular assessment of these phenomena which threaten seriously the implementation of the national tuberculosis control programme.
Kizub, D; Ghali, I; Sabouni, R; Bourkadi, J E; Bennani, K; El Aouad, R; Dooley, K E
In Morocco, tuberculosis (TB) treatment default is increasing in some urban areas. To provide a detailed description of factors that contribute to patient default and solutions from the point of view of health care professionals who participate in TB care. In-depth interviews were conducted with 62 physicians and nurses at nine regional public pulmonary clinics and local health clinics. Participants had a median of 24 years of experience in health care. Treatment default was seen as a result of multilevel factors related to the patient (lack of means, being a migrant worker, distance to treatment site, poor understanding of treatment, drug use, mental illness), medical team (high patient load, low motivation, lack of resources for tracking defaulters), treatment organization (poor communication between treatment sites, no systematic strategy for patient education or tracking, incomplete record keeping), and health care system and society. Tailored recommendations for low- and higher-cost interventions are provided. Interventions to enhance TB treatment completion should take into account the local context and multilevel factors that contribute to default. Qualitative studies involving health care workers directly involved in TB care can be powerful tools to identify contributing factors and define strategies to help reduce treatment default.
Bax, Hannelore I; Bakker-Woudenberg, Irma A J M; de Vogel, Corné P; van der Meijden, Aart; Verbon, Annelies; de Steenwinkel, Jurriaan E M
Novel treatment strategies for tuberculosis are urgently needed. Many different preclinical models assessing anti-tuberculosis drug activity are available, but it is yet unclear which combination of models is most predictive of clinical treatment efficacy. The aim of this study was to determine the role of our in vitro time kill-kinetics assay as an asset to a predictive preclinical modeling framework assessing anti-tuberculosis drug activity. The concentration- and time-dependent mycobacterial killing capacities of six anti-tuberculosis drugs were determined during exposure as single drugs or in dual, triple and quadruple combinations towards a Mycobacterium tuberculosis Beijing genotype strain and drug resistance was assessed. Streptomycin, rifampicin and isoniazid were most active against fast-growing M. tuberculosis. Isoniazid with rifampicin or high dose ethambutol were the only synergistic drug combinations. The addition of rifampicin or streptomycin to isoniazid prevented isoniazid resistance. In vitro ranking showed agreement with early bactericidal activity in tuberculosis patients for some but not all anti-tuberculosis drugs. The time-kill kinetics assay provides important information on the mycobacterial killing dynamics of anti-tuberculosis drugs during the early phase of drug exposure. As such, this assay is a valuable component of the preclinical modeling framework. Copyright © 2017 Elsevier Ltd. All rights reserved.
Izzettin Fikret V
Full Text Available Abstract Background The first line anti-tuberculosis drugs isoniazid (INH, rifampicin (RIF and pyrazinamide (PZA continues to be the effective drugs in the treatment of tuberculosis, however, the use of these drugs is associated with toxic reactions in tissues, particularly in the liver, leading to hepatitis. Silymarin, a standard plant extract with strong antioxidant activity obtained from S. marianum, is known to be an effective agent for liver protection and liver regeneration. The aim of this study was to investigate the protective actions of silymarin against hepatotoxicity caused by different combinations of anti-tuberculosis drugs. Methods Male Wistar albino rats weighing 250–300 g were used to form 6 study groups, each group consisting of 10 rats. Animals were treated with intra-peritoneal injection of isoniazid (50 mg/kg and rifampicin (100 mg/kg; and intra-gastric administration of pyrazinamid (350 mg/kg and silymarin (200 mg/kg. Hepatotoxicity was induced by a combination of drugs with INH+RIF and INH+RIF+PZA. Hepatoprotective effect of silymarin was investigated by co-administration of silymarin together with the drugs. Serum biochemical tests for liver functions and histopathological examination of livers were carried out to demonstrate the protection of liver against anti-tuberculosis drugs by silymarin. Results Treatment of rats with INH+RIF or INH+RIF+PZA induced hepatotoxicity as evidenced by biochemical measurements: serum alanine aminotransferase (ALT, aspartate aminotransferase (AST and alkaline phosphatase (ALP activities and the levels of total bilirubin were elevated, and the levels of albumin and total protein were decreased in drugs-treated animals. Histopathological changes were also observed in livers of animals that received drugs. Simultaneous administration of silymarin significantly decreased the biochemical and histological changes induced by the drugs. Conclusion The active components of silymarin had
Perdhana, Raditya; Sutrisno, Sutrisno; Sugiri, Yani Jane; Baktiyani, Siti Candra Windu; Wiyasa, Arsana
Tuberculosis (TB) is a disease which can affect various organs, including human's genital organs such as the endometrium. Tuberculosis endometritis can cause clinical symptoms of secondary amenorrhea and infertility. Infertility in genital TB caused by the involvement of the endometrium. The case presentation is 33-year-old woman from dr. Saiful Anwar Public Hospital to consult that she has not menstruated since 5 years ago (28 years old). The diagnosis was done by performing a clinical examination until the diagnosis of secondary amenorrhea due to tuberculosis endometritis is obtained. A treatment by using category I of anti-tuberculosis drugs was done for 6 months, afterward an Anatomical Pathology observation found no signs of the tuberculosis symptoms. Based on that, patient, who was diagnosed to have secondary amenorrhea due to tuberculosis endometritis, has no signs of tuberculosis process after being treated by using category I of anti-tuberculosis drugs for 6 months.
Bate, R; Jensen, P; Hess, K; Mooney, L; Milligan, J
Pharmacies in 19 cities in Angola, Brazil, China, Democratic Republic of Congo, Egypt, Ethiopia, Ghana, India (n = 3), Kenya, Nigeria, Russia, Rwanda, Thailand, Turkey, Uganda, United Republic of Tanzania and Zambia. To assess the quality of the two main first-line anti-tuberculosis medicines, isoniazid and rifampicin, procured from private-sector pharmacies, to determine if substandard and falsified medicines are available and if they potentially contribute to drug resistance in cities in low- and middle-income countries. Local nationals procured 713 treatment packs from a selection of pharmacies in 19 cities. These samples were tested for quality using 1) thin-layer chromatography to analyze levels of active pharmaceutical ingredient (API), and 2) disintegration testing. Of 713 samples tested, 9.1% failed basic quality testing for requisite levels of API or disintegration. The failure rate was 16.6% in Africa, 10.1% in India, and 3.9% in other middle-income countries. Substandard and falsified drugs are readily available in the private marketplace and probably contribute to anti-tuberculosis drug resistance in low- and middle-income countries. This issue warrants further investigation through large-scale studies of drug quality in all markets.
Silva, M R; Pereira, J C; Costa, R R; Dias, J A; Guimarães, M D C; Leite, I C G
This study aimed to evaluate the risk factors for tuberculosis (TB) treatment default in a priority city for disease control in Brazil. A cohort of TB cases diagnosed from 2008 to 2009 was followed up from patients' entry into three outpatient sites, in Juiz de Fora, Minas Gerais (Brazil), until the recording of the outcomes. Drug addiction, alcoholism and treatment site appeared to be independently associated with default. Current users of crack as the hardest drug (odds ratio (OR) 12·25, 95% confidence interval (CI) 3·04-49·26) were more likely to default than other hard drug users (OR 5·67, 95% CI 1·34-24·03), former users (OR 4·12, 95% CI 1·11-15·20) and those not known to use drugs (reference group). Consumers at high risk of alcoholism (OR 2·94, 95% CI 1·08-7·99) and those treated in an outpatient hospital unit (OR 8·22, 95% CI 2·79-24·21%) also were more likely to default. Our results establish that substance abuse was independently associated with default. National TB programmes might be more likely to achieve their control targets if they include interventions aimed at improving adherence and cure rates, by diagnosing and treating substance abuse concurrently with standard TB therapy.
Lalor, Maeve K; Greig, Jane; Allamuratova, Sholpan; Althomsons, Sandy; Tigay, Zinaida; Khaemraev, Atadjan; Braker, Kai; Telnov, Oleksander; du Cros, Philipp
The Médecins Sans Frontières project of Uzbekistan has provided multidrug-resistant tuberculosis treatment in the Karakalpakstan region since 2003. Rates of default from treatment have been high, despite psychosocial support, increasing particularly since programme scale-up in 2007. We aimed to determine factors associated with default in multi- and extensively drug-resistant tuberculosis patients who started treatment between 2003 and 2008 and thus had finished approximately 2 years of treatment by the end of 2010. A retrospective cohort analysis of multi- and extensively drug-resistant tuberculosis patients enrolled in treatment between 2003 and 2008 compared baseline demographic characteristics and possible risk factors for default. Default was defined as missing ≥60 consecutive days of treatment (all drugs). Data were routinely collected during treatment and entered in a database. Potential risk factors for default were assessed in univariate analysis using chi-square test and in multivariate analysis with logistic regression. 20% (142/710) of patients defaulted after a median of 6 months treatment (IQR 2.6-9.9). Factors associated with default included severity of resistance patterns (pre-extensively drug-resistant/extensively drug-resistant tuberculosis adjusted odds ratio 0.52, 95%CI: 0.31-0.86), previous default (2.38, 1.09-5.24) and age >45 years (1.77, 1.10-2.87). The default rate was 14% (42/294) for patients enrolled 2003-2006 and 24% (100/416) for 2007-2008 enrolments (p = 0.001). Default from treatment was high and increased with programme scale-up. It is essential to ensure scale-up of treatment is accompanied with scale-up of staff and patient support. A successful first course of tuberculosis treatment is important; patients who had previously defaulted were at increased risk of default and death. The protective effect of severe resistance profiles suggests that understanding disease severity or fear may motivate against default. Targeted
Full Text Available Background: Private health care providers are largely the first point of contact for Tuberculosis (TB patients, who either undergo treatment from private practitioners or buy medicines on their own from private pharmacies. Aims: This study assessed the availability, sale and magnitude of anti-tuberculosis drugs dispensing through private pharmacies. Methodology: The present cross sectional study was conducted among private pharmacies located along the national highway from Thalassery to Payyannur in the Kannur district of Kerala, India. A total of 38 private pharmacies located along the national highway were included. Results: The duration that anti–TB drugs had been on sale showed that 74.3% of pharmacies had started to sell these drugs only less than ten years ago. The majority (82.9% of the private pharmacies received up to 5 prescriptions for anti-TB drugs weekly. Out of the total of 35 pharmacies selling these drugs, 22 (62.9% reported an increase in their sales. Nearly 82% of those pharmacies that reported an increase in the sale of anti-TB drugs were selling these drugs for less than the past ten years. Conclusions: The current study shows that a large number of tuberculosis patients are still approaching private pharmacies for anti-tuberculosis drugs. This tendency has to be completely stopped and needs properly planned strategies to encourage private pharmacies to participate actively in the DOTS (Direct Observation Treatment Short course program of the Government, by providing them attractive alternative incentives
Background: Private health care providers are largely the first point of contact for Tuberculosis (TB patients, who either undergo treatment from private practitioners or buy medicines on their own from private pharmacies. Aims: This study assessed the availability, sale and magnitude of anti-tuberculosis drugs dispensing through private pharmacies.
Methodology: The present cross sectional study was conducted among private pharmacies located along the national highway from Thalassery to Payyannur in the Kannur district of Kerala, India. A total of 38 private pharmacies located along the national highway were included.
Results: The duration that anti–TB drugs had been on sale showed that 74.3% of pharmacies had started to sell these drugs only less than ten years ago. The majority (82.9% of the private pharmacies received up to 5 prescriptions for anti-TB drugs weekly. Out of the total of 35 pharmacies selling these drugs, 22 (62.9% reported an increase in their sales. Nearly 82% of those pharmacies that reported an increase in the sale of anti-TB drugs were selling these drugs for less than the past ten years.
Conclusions: The current study shows that a large number of tuberculosis patients are still approaching private pharmacies for anti-tuberculosis drugs. This tendency has to be completely stopped and needs properly planned strategies to encourage private pharmacies to participate actively in the DOTS (Direct Observation Treatment Short course program of the Government, by providing them attractive alternative incentives
Full Text Available Non-adherence to tuberculosis therapy can lead to drug resistance, prolonged infectiousness, and death; therefore, understanding what causes treatment default is important. Pakistan has one of the highest burdens of tuberculosis in the world, yet there have been no qualitative studies in Pakistan that have specifically examined why default occurs. We conducted a mixed methods study at a tuberculosis clinic in Karachi to understand why patients with drug-susceptible tuberculosis default from treatment, and to identify factors associated with default. Patients attending this clinic pick up medications weekly and undergo family-supported directly observed therapy.In-depth interviews were administered to 21 patients who had defaulted. We also compared patients who defaulted with those who were cured, had completed, or had failed treatment in 2013.Qualitative analyses showed the most common reasons for default were the financial burden of treatment, and medication side effects and beliefs. The influence of finances on other causes of default was also prominent, as was concern about the effect of treatment on family members. In quantitative analysis, of 2120 patients, 301 (14.2% defaulted. Univariate analysis found that male gender (OR: 1.34, 95% CI: 1.04-1.71, being 35-59 years of age (OR: 1.54, 95% CI: 1.14-2.08, or being 60 years of age or older (OR: 1.84, 95% CI: 1.17-2.88 were associated with default. After adjusting for gender, disease site, and patient category, being 35-59 years of age (aOR: 1.49, 95% CI: 1.10-2.03 or 60 years of age or older (aOR: 1.76, 95% CI: 1.12-2.77 were associated with default.In multivariate analysis age was the only variable associated with default. This lack of identifiable risk factors and our qualitative findings imply that default is complex and often due to extrinsic and medication-related factors. More tolerable medications, improved side effect management, and innovative cost-reduction measures are needed to
Chida, Natasha; Ansari, Zara; Hussain, Hamidah; Jaswal, Maria; Symes, Stephen; Khan, Aamir J; Mohammed, Shama
Non-adherence to tuberculosis therapy can lead to drug resistance, prolonged infectiousness, and death; therefore, understanding what causes treatment default is important. Pakistan has one of the highest burdens of tuberculosis in the world, yet there have been no qualitative studies in Pakistan that have specifically examined why default occurs. We conducted a mixed methods study at a tuberculosis clinic in Karachi to understand why patients with drug-susceptible tuberculosis default from treatment, and to identify factors associated with default. Patients attending this clinic pick up medications weekly and undergo family-supported directly observed therapy. In-depth interviews were administered to 21 patients who had defaulted. We also compared patients who defaulted with those who were cured, had completed, or had failed treatment in 2013. Qualitative analyses showed the most common reasons for default were the financial burden of treatment, and medication side effects and beliefs. The influence of finances on other causes of default was also prominent, as was concern about the effect of treatment on family members. In quantitative analysis, of 2120 patients, 301 (14.2%) defaulted. Univariate analysis found that male gender (OR: 1.34, 95% CI: 1.04-1.71), being 35-59 years of age (OR: 1.54, 95% CI: 1.14-2.08), or being 60 years of age or older (OR: 1.84, 95% CI: 1.17-2.88) were associated with default. After adjusting for gender, disease site, and patient category, being 35-59 years of age (aOR: 1.49, 95% CI: 1.10-2.03) or 60 years of age or older (aOR: 1.76, 95% CI: 1.12-2.77) were associated with default. In multivariate analysis age was the only variable associated with default. This lack of identifiable risk factors and our qualitative findings imply that default is complex and often due to extrinsic and medication-related factors. More tolerable medications, improved side effect management, and innovative cost-reduction measures are needed to reduce
Nnamdi O. Ndubuka
Full Text Available Background: Antiretroviral therapy (ART improves patients’ health-related quality of life (HRQoL. Defaulting from ART has detrimental consequences, including the development of viral resistance, treatment failure and increased risks of disease progression. Little is known about the quality of life of ART defaulters and reasons for discontinuing their ART. Objectives: This study sought to measure the HRQoL of ART patients in Botswana who were on ART for up to 5 years but had discontinued treatment for at least 3 months, and to identify factors associated with ART defaulting. Method: We conducted a cross-sectional study with 104 eligible respondents in four ART clinics in south eastern Botswana. We assessed respondents’ HRQoL using the World Health Organization Quality of Life Questionnaire for HIV short form. Clinical information was obtained from respondents’ medical records. Data were analysed using SAS version 9.2. Results: Reasons for discontinuing ART were inaccessible clinics (22.4%, feeling better (21.4%, running out of pills (11.2%, depression (8.2%, lack of care and/or support (8.2%, failure to understand instructions (7.7%, medications’ side effects (6.1% and alcohol abuse (3.1%. In multivariate analyses, respondents aged 36–45 years had a 0.03 lower independence HRQoL score compared to those aged 35 and younger (β = -0.03; 95% confidence interval: -1.72, -1.66. Despite defaulting from their ART, respondents’ calculated HRQoL scores were Conclusion: This study highlights the need to enhance ART adherence in order to improve the HRQoL of people living with HIV and/or AIDS.
Prognostic significance of the intervals between the initiation of antiretroviral therapy and anti-tuberculosis treatment in HIV-tuberculosis co-infected patients: Results from the TREAT Asia HIV Observational Database
Han, Sang Hoon; Zhou, Jialun; Lee, Man Po; Zhao, Hongxin; Chen, Yi-Ming Arthur; Kumarasamy, Nagalingeswaran; Pujari, Sanjay; Lee, Christopher; Faridah Syed Omar, Sharifah; Ditangco, Rossana; Phanuphak, Nittaya; Kiertiburanakul, Sasisopin; Chaiwarith, Romanee; Merati, Tuti Parwati; Yunihastuti, Evy; Tanuma, Junko; Saphonn, Vonthanak; Sohn, Annette H.; Choi, Jun Yong
Objectives We evaluated the effect of time intervals between the initiation of antiretroviral therapy (ART) and tuberculosis (TB) treatment on clinical outcomes in HIV-TB co-infected patients in an Asian regional cohort. Methods Adult HIV-TB co-infected patients in an observational HIV cohort database who had a known date of ART initiation and history of TB treatment were eligible for study inclusion. The time intervals between the initiation of ART and TB treatment were categorized as follows: TB diagnosed while on ART, early ART (ART (>90 days after TB treatment), and ART not started. Outcomes were assessed using survival analyses. Results A total of 768 HIV-TB co-infected patients were included in this study. Median CD4 T-cell count at TB diagnosis was 100 (IQR 40–208) cells/µL. The treatment outcomes between early ART and delayed ART initiation were not significantly different. Kaplan-Meier analysis indicated that mortality was highest for those diagnosed with TB while on ART (3.77 deaths per 100 person-years), and the prognoses of other groups were not different (in deaths per 100 person-years: 2.12 early ART, 1.46 delayed ART, and 2.94 ART not started). In a multivariate model, the interval between ART initiation and TB therapy did not significantly impact all-cause mortality. Conclusions The negative impact of delayed ART in patients co-infected with TB was not observed in this observational cohort of moderately to severely immunosuppressed patients. The broader impact of earlier ART in actual clinical practice should be monitored more closely. PMID:23980589
Full Text Available The classification of anti-tuberculosis (TB drugs is important as it helps the clinician to build an appropriate anti-TB regimen for multidrug-resistant (MDR and extensively drug-resistant (XDR TB cases that do not fulfil the criteria for the shorter MDR-TB regimen. The World Health Organization (WHO has recently approved a revision of the classification of new anti-TB drugs based on current evidence on each drug. In the previous WHO guidelines, the choice of drugs was based on efficacy and toxicity in a step-down manner, from group 1 first-line drugs and groups 2–5 second-line drugs, to group 5 drugs with potentially limited efficacy or limited clinical evidence. In the revised WHO classification, exclusively aimed at managing drug-resistant cases, medicines are again listed in hierarchical order from group A to group D. In parallel, a possible future classification is independently proposed. The aim of this viewpoint article is to describe the evolution in WHO TB classification (taking into account an independently proposed new classification and recent changes in WHO guidance, while commenting on the differences between them. The latest evidence on the ex-group 5 drugs is also discussed.
Kansal, S; Chakravarty, J; Kumar, A; Malaviya, P; Boelaert, M; Hasker, E; Ostyn, B; Sundar, S
To assess the rate of default from treatment in the visceral leishmaniasis (VL) elimination programme and to identify risk factors and its underlying causes. Case-control study conducted between December 2009 and June 2012 in three primary health centres (PHCs) of Muzaffarpur district, India. Patients who defaulted from treatment from the PHCs were considered as 'cases' and those who completed their treatment as 'controls'. Two controls were included in the study for each case. Respondents' opinion and satisfaction with the services provided at the PHCs were also elicited. Logistic regression was performed to assess the contribution of sociodemographic variables on patient status, and a discriminant analysis was used (after decomposing the original data) to identify factors that can predict the patient status as defaulter or not, based on factor scores of the components as predictor variables. During the study period, 16.3% (89/544) of patients defaulted; 87 cases and 188 controls were interviewed through a semistructured questionnaire. Women tended to be more at risk for default (OR, 1.6, 95% CI (0.9 -2.9). Treatment received was miltefosine in 55.6% and sodium stibogluconate (SSG) in 44.4%. Most (86%) defaulters completed their treatment at other healthcare facilities; 70% of them preferred non-governmental institutions. Most cited reasons for default were seeking a second opinion for VL treatment and preferring to be treated in specialised VL centres. Discriminant analysis showed only one significant predictor: dissatisfaction with the medical care received in PHCs. Efforts are needed to enhance the quality of VL care at PHC level, which will be beneficial in increasing treatment completion rates. © 2017 John Wiley & Sons Ltd.
Niu, Xuan; Zhang, Ming; Liu, Zhenyu; Bai, Lijun; Sun, Chuanzhu; Wang, Shan; Wang, Xiaocui; Chen, Zhen; Chen, Hongyan; Tian, Jie
Appropriate selection of ipsilateral or contralateral electroacupuncture (corresponding to the pain site) plays an important role in reaching its better curative effect; however, the involving brain mechanism still remains unclear. Compared with the heat pain model generally established in previous study, capsaicin pain model induces reversible cutaneous allodynia and is proved to be better simulating aspects of clinical nociceptive and neuropathic pain. In the current study, 24 subjects were randomly divided into two groups with a 2 × 2 factorial design: laterality (ipsi- or contralateral side, inter-subject) × treatment with counter-balanced at an interval of one week (verum and placebo electroacupuncture, within-subject). We observed subjective pain intensity and brain activations changes induced by capsaicin allodynia pain stimuli before and after electroacupuncture treatment at acupoint LI4 for 30 min. Analysis of variance results indicated that ipsilateral electroacupuncture treatment produced significant pain relief and wide brain signal suppressions in pain-related brain areas compared with contralateral electroacupuncture. We also found that verum electroacupuncture at either ipsi- or contralateral side to the pain site exhibited comparable significant magnitudes of analgesic effect. By contrast, placebo electroacupuncture elicited significant pain reductions only on the ipsilateral rather than contralateral side. It was inferred that placebo analgesia maybe attenuated on the region of the body (opposite to pain site) where attention was less focused, suggesting that analgesic effect of placebo electroacupuncture mainly rely on the motivation of its spatial-specific placebo responses via attention mechanism. This inference can be further supported by the evidence that the significant interaction effect of manipulation laterality and treatment was exclusively located within the default mode network, including the bilateral superior parietal
Erlenmaier, Ulrich; Gersbach, Hans
Starting from the Merton framework for firm defaults, we provide the analytics and robustness of the relationship between default correlations. We show that loans with higher default probabilities will not only have higher variances but also higher correlations between loans. As a consequence, portfolio standard deviation can increase substantially when loan default probabilities rise. This result has two important implications. First, relative prices of loans with different default probabili...
Martin, Sherry Joseph; Baskaran, Udhaya Lavinya; Vedi, Mahima; Sabina, Evan Prince
Therapy using Isoniazid (INH) and Rifampicin (RIF) leads to induction of hepatotoxicity in some individuals undergoing anti-tuberculosis treatment. In this study, we assessed the effect of Spirulina fusiformis on INH and RIF induced hepatotoxicity in rats compared with hepatoprotective drug Silymarin. Induction of hepatotoxicity was measured by changes in the liver marker enzymes (aspartate transaminase, alanine transaminase, and alkaline phosphatase). The antioxidant status was also analyzed in liver tissue homogenate and plasma by measurement of superoxide dismutase, catalase, glutathione-S-transferase, glutathione reductase, and lipid peroxidation levels. We also aimed to study the binding and interactions of the transcription factors Pregnane X Receptor (PXR) and Farnesoid X Receptor (FXR) with INH, RIF, and representative active compounds of Spirulina fusiformis by in silico methods. The administration of INH and RIF resulted in significant (p Spirulina fusiformis was seen to protect the parameters from significant changes upon challenge with INH and RIF in a dose-dependent manner. This was corroborated by histological examination of the liver. The results of the in silico analyses further support the wet lab results.
Altmann, Steffen; Falk, Armin; Heidhues, Paul
We study how website defaults affect consumer behavior in the domain of charitable giving. In a field experiment that was conducted on a large platform for making charitable donations over the web, we exogenously vary the default options in two distinct choice dimensions. The first pertains...... to the primary donation decision, namely, how much to contribute to the charitable cause. The second relates to an "add-on" decision of how much to contribute to supporting the online platform itself. We find a strong impact of defaults on individual behavior: in each of our treatments, the modal positive...... contributions in both choice dimensions invariably correspond to the specified default amounts. Defaults, nevertheless, have no impact on aggregate donations. This is because defaults in the donation domain induce some people to donate more and others to donate less than they otherwise would have. In contrast...
Kay, Benjamin P; DiFrancesco, Mark W; Privitera, Michael D; Gotman, Jean; Holland, Scott K; Szaflarski, Jerzy P
Summary Purpose Idiopathic generalized epilepsy (IGE) resistant to treatment is common, but its neuronal correlates are not entirely understood. Thus, the aim of this study was to examine resting-state default mode network (DMN) functional connectivity in patients with treatment-resistant IGE. Methods Treatment-resistance was defined as continuing seizures despite an adequate dose of valproic acid (valproate, VPA). Data from 60 epilepsy patients and 38 healthy controls who underwent simultaneous EEG and resting-state fMRI were included (EEG/fMRI). Independent component analysis (ICA) and dual regression were used to quantify DMN connectivity. Confirmatory analysis using seed-based voxel correlation was performed. Key Findings There was a significant reduction of DMN connectivity in patients with treatment-resistant epilepsy when compared to patients who were treatment-responsive and healthy controls. Connectivity was negatively correlated with duration of epilepsy. Significance Our findings in this large sample of patients with IGE indicate the presence of reduced DMN connectivity in IGE and show that connectivity is further reduced in treatment-resistant epilepsy. DMN connectivity may be useful as a biomarker for treatment-resistance. PMID:23293853
Al Amad, Mohammed; Al-Eryani, Lina; Al Serouri, Abdulwahed; Khader, Yousef S
This study aimed to measure the treatment default rate among children with severe acute malnutrition (SAM) who were admitted to the outpatient therapeutic programme (OTP) in Yemen and determine its risk factors. A prospective study was conducted among children with SAM who were newly admitted to the 11 OTPs in primary health centres of Sana'a city. A pretested semistructured questionnaire was used for data collection at admission and at after 2 months of admission to the OTP. Univariate and multivariate analysis using binary logistic regression were used to analyse the risk factors of treatment default. This study included 339 SAM children. Of those, 186 (55%) children discharged as defaulters, 141 (42%) were cured, and 12 (3%) were transferred to other treatment sites. Many factors related to poor accessibility, poor satisfaction with staff and system, and treatment and acceptability of OTP services factors were significantly associated with treatment default. Having difficulty to attend OTP every week (OR 8.4), unavailability of medication during follow-up visits (OR 5.0), not liking to eat Plumpy'Nut (OR 5.8), and not gaining weight since the start of treatment (OR 9.3) were the strongest predictors of treatment default. This study showed a high default rate among SAM children in Sana'a city. Factors related to poor accessibility, poor satisfaction with staff and system, and factors related to treatment and acceptability of OTP services were significantly associated with high default rate. Expansion of OTP services and training OTPs staff on SAM treatment protocols are highly recommended. © 2017 John Wiley & Sons, Ltd.
Ma, Junying; Huang, Hongbo; Xie, Yunchang; Liu, Zhiyong; Zhao, Jin; Zhang, Chunyan; Jia, Yanxi; Zhang, Yun; Zhang, Hua; Zhang, Tianyu; Ju, Jianhua
Tuberculosis remains one of the world's deadliest communicable diseases, novel anti-tuberculosis agents are urgently needed due to severe drug resistance and the co-epidemic of tuberculosis/human immunodeficiency virus. Here, we show the isolation of six anti-mycobacterial ilamycin congeners (1-6) bearing rare L-3-nitro-tyrosine and L-2-amino-4-hexenoic acid structural units from the deep sea-derived Streptomyces atratus SCSIO ZH16. The biosynthesis of the rare L-3-nitrotyrosine and L-2-amino-4-hexenoic acid units as well as three pre-tailoring and two post-tailoring steps are probed in the ilamycin biosynthetic machinery through a series of gene inactivation, precursor chemical complementation, isotope-labeled precursor feeding experiments, as well as structural elucidation of three intermediates (6-8) from the respective mutants. Most impressively, ilamycins E 1 /E 2 , which are produced in high titers by a genetically engineered mutant strain, show very potent anti-tuberculosis activity with an minimum inhibitory concentration value ≈9.8 nM to Mycobacterium tuberculosis H37Rv constituting extremely potent and exciting anti-tuberculosis drug leads.Tuberculosis (TB) remains one of the world's deadliest communicable diseases, novel anti-TB agents are urgently needed due to severe drug resistance and the co-epidemic of TB/HIV. Here, the authors show that anti-mycobacterial ilamycin congeners bearing unusual structural units possess extremely potent anti-tuberculosis activities.
Siripassorn, Krittaecho; Ruxrungtham, Kiat; Manosuthi, Weerawat
To evaluate the outcomes of anti-tuberculosis drug desensitization. This was a retrospective study. Inclusion criteria were as follows: age >18years, documented tuberculosis infection, a previous cutaneous allergic reaction to anti-tuberculosis drugs, and having undergone drug desensitization between January 2003 and March 2014. The definition of allergic reaction to anti-tuberculosis drugs included (1) a temporal relationship between drug use and the allergic reaction; (2) improvement in the allergic reaction after drug withdrawal; (3) recurrence of the allergic reaction after reintroduction of only the offending drug; and (4) absence of other causes. A total of 19 desensitization procedures were performed. The drugs used for these procedures were isoniazid (n=7), rifampicin (n=6), or ethambutol (n=6). Of note, severe allergic reactions (Stevens-Johnson syndrome (n=4), erythema multiforme (n=3), and drug rash with eosinophilia and systemic syndrome (n=1)) were included. All patients underwent resolution of the previous allergic reactions before desensitization. The median duration of desensitization was 18 days. The success rate was 78.9%. The allergic reactions following failed desensitization were not severe; most were maculopapular rashes. The desensitization protocol for anti-tuberculosis drugs was associated with a high success rate, and the individuals who failed desensitization experienced mild allergic reactions. Copyright © 2018 The Author(s). Published by Elsevier Ltd.. All rights reserved.
Kamal, S M M; Hossain, A; Sultana, S; Begum, V; Haque, N; Ahmed, J; Rahman, T M A; Hyder, K A; Hossain, S; Rahman, M; Ahsan, Chowdhury R; Chowdhury, R A; Aung, K J M; Islam, A; Hasan, R; Van Deun, A
To determine the prevalence of tuberculosis (TB) drug resistance in Bangladesh. Weighted cluster sampling among smear-positive cases, and standard culture and drug susceptibility testing on solid medium were used. Of 1480 patients enrolled during 2011, 12 falsified multidrug-resistant TB (MDR-TB) patients were excluded. Analysis included 1340 cases (90.5% of those enrolled) with valid results and known treatment antecedents. Of 1049 new cases, 12.3% (95%CI 9.3-16.1) had strains resistant to any of the first-line drugs tested, and 1.4% (95%CI 0.7-2.5) were MDR-TB. Among the 291 previously treated cases, this was respectively 43.2% (95%CI 37.1-49.5) and 28.5% (95%CI 23.5-34.1). History of previous anti-tuberculosis treatment was the only predictive factor for first-line drug resistance (OR 34.9). Among the MDR-TB patients, 19.2% (95%CI 11.3-30.5; exclusively previously treated) also showed resistance to ofloxacin. Resistance to kanamycin was not detected. Although MDR-TB prevalence was relatively low, transmission of MDR-TB may be increasing in Bangladesh. MDR-TB with fluoroquinolone resistance is rapidly rising. Integrating the private sector should be made high priority given the excessive proportion of MDR-TB retreatment cases in large cities. TB control programmes and donors should avoid applying undue pressure towards meeting global targets, which can lead to corruption of data even in national surveys.
Mulders, Peter C R; van Eijndhoven, Philip F P; Pluijmen, Joris; Schene, Aart H; Tendolkar, Indira; Beckmann, Christian F
Functional connectivity in the "default mode network" (DMN) is changed in depression, and evidence suggests depression also affects the DMN's spatial topography and might cause a dissociation between its anterior and posterior regions. As antidepressive treatment affects anterior and posterior regions of the network differently, how depression and treatment change DMN-organization is crucial for understanding their mechanisms. We present a novel way of assessing the coherence of a network's regions to the network as a whole, and apply this to investigate treatment-resistant depression and the effects of electroconvulsive therapy (ECT). Resting-state functional MRI was collected from 16 patients with treatment-resistant depression before and after ECT and 16 healthy controls matched for age and sex. For each subject, the mean time series of the DMN was used as a regressor for each voxel within the DMN, creating a map of "network coherence" (NC). The obtained maps were compared across groups using permutation testing. NC was significantly decreased in depressed subjects in the precuneus and the angular gyrus. With ECT the NC normalized in responders (n=8), but not in non-responders (n=8). We present a novel method of investigating within-network coherence and apply this to show that in depression, a large area of the DMN shows a decrease in coherence to the network as a whole. Although tentative due to the small sample size, we find that this effect is not present after ECT in those improving clinically, but persists in patients not responding to ECT. Copyright © 2016 Elsevier B.V. All rights reserved.
Cui, Xilong; Guo, Wenbin; Wang, Yi; Yang, Tian-Xiao; Yang, Xin-Hua; Wang, Yefei; Gong, Jingbo; Tan, Changlian; Xie, Guangrong
Melancholic depression is a relatively homogenous subtype of major depressive disorders (MDD). The condition has several endogenous symptoms and represents strong biological components. However, its specific neurobiological mechanisms remain unknown. Previous neuroimaging findings indicated that default mode network (DMN) is closely related to MDD. The present study examined the network homogeneity (NH) of the DMN in patients with melancholic MDD. A total of 33 first-episode, treatment-naive melancholic MDD patients and 32 healthy controls underwent a resting-state functional magnetic resonance imaging scan. The data were analyzed using the NH method. Compared with healthy controls, patients with melancholic MDD showed low NH values in the right middle temporal gyrus and temporal pole (MTG/TP). The abnormal NH of this region and clinical characteristics were not correlated. Abnormal NH pattern of DMN exists in patients with melancholic MDD. This feature may be part of the pathophysiological basis of this disorder. Copyright © 2016 Elsevier B.V. All rights reserved.
Jain, Puneet P; Degani, Mariam S; Raju, Archana; Anantram, Aarti; Seervi, Madhav; Sathaye, Sadhana; Ray, Muktikanta; Rajan, M G R
A series of novel quinoline-oxadiazole hybrid compounds was designed based on stepwise rational modification of the lead molecules reported previously, in order to enhance bioactivity and improve druglikeness. The hybrid compounds synthesized were screened for biological activity against Mycobacterium tuberculosis H37Rv and for cytotoxicity in HepG2 cell line. Several of the hits exhibited good to excellent anti-tuberculosis activity and selectivity, especially compounds 12m, 12o and 12p, showed minimum inhibitory concentration values500. The results of this study open up a promising avenue that may lead to the discovery of a new class of anti-tuberculosis agents. Copyright © 2015 Elsevier Ltd. All rights reserved.
Zhang, Lin; Li, Ruyi; Li, Mengzhu; Qi, Zhongjie; Tian, Jingkui
This study was designed to investigate the anti-tuberculosis activities of Ranunculi Ternati Radix extracts to demonstrate the effect of active part of Ranunculi Ternati Radix, which could be enriched through macroporous resin, on mycobacterium tuberculosis infections. In vitro, the anti-tuberculosis activity of its water extract (WE), 70% ethanol extract (EE), water eluted part of EE from D101 macroporous resin (WEPMR), 70% ethanol eluted part of EE from D101 macroporous resin (EEPMR) was conducted using H37Rv. Then EEPMR of better anti-tuberculosis activity was chosen to carry out anti-tuberculosis activity test against MDR2314-2 and XDR1220. In vivo, the anti-tuberculosis activities of EEPMR, Ranunculi Ternati Capsules and Isoniazid alone or in combination with different doses were evaluated on mouse model infected H37Rv. In vitro, EEPMR had inhibitory effect on H37Rv, MDR2314-2 and XDR1220. In vivo study, both medium and high dose of EEPMR alone had therapeutic effect on chronic tuberculosis in mouse. No acute toxicity was identified of EEPMR at a dose of 12.0 g·kg-1. EEPMR possessed better anti-tuberculosis effects than other extracts and Radix Ranunculi Ternati Capsules. This supported the use of macroporous resin to enrich the active part of Ranunculi Ternati Radix to cure mycobacterium tuberculosis infections.
Geng, Xiujuan; Hu, Yuzheng; Gu, Hong; Salmeron, Betty Jo; Adinoff, Bryon; Stein, Elliot A; Yang, Yihong
While chronic cocaine use is associated with abnormalities in both brain structure and function within and interactions between regions, previous studies have been limited to interrogating structure and function independently, and the detected neural differences have not been applied to independent samples to assess the clinical relevance of results. We investigated consequences of structural differences on resting-state functional connectivity in cocaine addiction and tested whether resting-state functional connectivity of the identified circuits predict relapse in an independent cohort. Subjects included 64 non-treatment-seeking cocaine users (NTSCUs) and 67 healthy control subjects and an independent treatment-completed cohort (n = 45) of cocaine-dependent individuals scanned at the end of a 30-day residential treatment programme. Differences in cortical thickness and related resting-state functional connectivity between NTSCUs and healthy control subjects were identified. Survival analysis, applying cortical thickness of the identified regions, resting-state functional connectivity of the identified circuits and clinical characteristics to the treatment cohort, was used to predict relapse. Lower cortical thickness in bilateral insula and higher thickness in bilateral temporal pole were found in NTSCUs versus healthy control subjects. Whole brain resting-state functional connectivity analyses with these four different anatomical regions as seeds revealed eight weaker circuits including within the salience network (insula seeds) and between temporal pole and elements of the default mode network in NTSCUs. Applying these circuits and clinical characteristics to the independent cocaine-dependent treatment cohort, functional connectivity between right temporal pole and medial prefrontal cortex, combined with years of education, predicted relapse status at 150 days with 88% accuracy. Deficits in the salience network suggest an impaired ability to process
Florian M Marx
Full Text Available RATIONALE: High rates of recurrent tuberculosis after successful treatment have been reported from different high burden settings in Sub-Saharan Africa. However, little is known about the rate of smear-positive tuberculosis after treatment default. In particular, it is not known whether or not treatment defaulters continue to be or become again smear-positive and thus pose a potential for transmission of infection to others. OBJECTIVE: To investigate, in a high tuberculosis burden setting, the rate of re-treatment for smear-positive tuberculosis among cases defaulting from standardized treatment compared to successfully treated cases. METHODS: Retrospective cohort study among smear-positive tuberculosis cases treated between 1996 and 2008 in two urban communities in Cape Town, South Africa. Episodes of re-treatment for smear-positive tuberculosis were ascertained via probabilistic record linkage. Survival analysis and Poisson regression were used to compare the rate of smear-positive tuberculosis after treatment default to that after successful treatment. RESULTS: A total of 2,136 smear-positive tuberculosis cases were included in the study. After treatment default, the rate of re-treatment for smear-positive tuberculosis was 6.86 (95% confidence interval [CI]: 5.59-8.41 per 100 person-years compared to 2.09 (95% CI: 1.81-2.41 after cure (adjusted Hazard Ratio [aHR]: 3.97; 95% CI: 3.00-5.26. Among defaulters, the rate was inversely associated with treatment duration and sputum conversion prior to defaulting. Smear grade at start of the index treatment episode (Smear3+: aHR 1.61; 95%CI 1.11-2.33 was independently associated with smear-positive tuberculosis re-treatment, regardless of treatment outcome. CONCLUSIONS: In this high-burden setting, there is a high rate of subsequent smear-positive tuberculosis after treatment default. Treatment defaulters are therefore likely to contribute to the pool of infectious source cases in the community. Our
Background Concomitant treatment of Human Immunodeficiency Virus (HIV) infection and tuberculosis (TB) presents a series of challenges for treatment compliance for both providers and patients. We carried out this study to identify risk factors for default from TB treatment in people living with HIV. Methods We conducted a cohort study to monitor HIV/TB co-infected subjects in Pernambuco, Brazil, on a monthly basis, until completion or default of treatment for TB. Logistic regression was used to calculate crude and adjusted odds ratios, 95% confidence intervals and P-values. Results From a cohort of 2310 HIV subjects, 390 individuals (16.9%) who had started treatment after a diagnosis of TB were selected, and data on 273 individuals who completed or defaulted on treatment for TB were analyzed. The default rate was 21.7% and the following risk factors were identified: male gender, smoking and CD4 T-cell count less than 200 cells/mm3. Age over 29 years, complete or incomplete secondary or university education and the use of highly active antiretroviral therapy (HAART) were identified as protective factors for the outcome. Conclusion The results point to the need for more specific actions, aiming to reduce the default from TB treatment in males, younger adults with low education, smokers and people with CD4 T-cell counts < 200 cells/mm3. Default was less likely to occur in patients under HAART, reinforcing the strategy of early initiation of HAART in individuals with TB. PMID:22176628
Matono, Takashi; Nishijima, Takeshi; Teruya, Katsuji; Morino, Eriko; Takasaki, Jin; Gatanaga, Hiroyuki; Kikuchi, Yoshimi; Kaku, Mitsuo; Oka, Shinichi
Little information exists on the frequency, severity, and timing of first-line anti-tuberculosis drug-related adverse events (TB-AEs) in HIV-tuberculosis coinfected (HIV-TB) patients in the antiretroviral therapy (ART) era. This matched-cohort study included HIV-TB patients as cases and HIV-uninfected tuberculosis (non-HIV-TB) patients as controls. Tuberculosis was culture-confirmed in both groups. Cases were matched to controls in a 1:4 ratio on age, sex, and year of diagnosis. TB-AEs were defined as Grade 2 or higher requiring drug discontinuation/regimen change. From 2003 to 2015, 94 cases and 376 controls were analyzed (95% men, 98% Asians). Standard four-drug combination therapy was initiated in 91% of cases and 89% of controls (p = 0.45). Cases had a higher frequency of TB-AE [51% (48/94) vs. 10% (39/376), p tuberculosis treatment. HIV infection was an independent risk factor for TB-AEs in the multivariate Cox analysis [adjusted HR (aHR): 6.96; 95% confidence interval: 3.93-12.3]. TB-AEs occurred more frequently in HIV-TB than in non-HIV-TB patients, and were more severe. The majority of TB-AEs occurred within 4 weeks of initiating anti-tuberculosis treatment. Because TB-AEs may delay ART initiation, careful monitoring during this period is warranted in coinfected patients.
Chesdachai, Supavit; Zughaier, Susu M; Hao, Li; Kempker, Russell R; Blumberg, Henry M; Ziegler, Thomas R; Tangpricha, Vin
Tuberculosis (TB) is a major global health problem. Patients with TB have a high rate of vitamin D deficiency, both at diagnosis and during the course of treatment with anti-tuberculosis drugs. Although data on the efficacy of vitamin D supplementation on Mycobacterium tuberculosis (Mtb) clearance is uncertain from randomized controlled trials (RCTs), vitamin D enhances the expression of the anti-microbial peptide human cathelicidin (hCAP18) in cultured macrophages in vitro. One possible explanation for the mixed (primarily negative) results of RCTs examining vitamin D treatment in TB infection is that anti-TB drugs given to enrolled subjects may impact actions of vitamin D to enhance cathelicidin in macrophages. To address this hypothesis, human macrophage-like monocytic (THP-1) cells were treated with varying doses of first-line anti-tuberculosis drugs in the presence of the active form of vitamin D, 1N1,25-dihydroxyvitamin D 3 (1,25(OH) 2 D 3 ). The expression of hCAP18 was determined by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). 1,25(OH) 2 D 3 strongly induced expression of hCAP18 mRNA in THP-1 cells (fold-change from control). The combination of the standard 4-drug TB therapy (isoniazid, rifampicin, pyrazinamide and ethambutol) in the cultured THP-1 cells demonstrated a significant decrease of hCAP18 mRNA at the dosage of 10 ug/mL. In 31 subjects with newly diagnosed drug-sensitive TB randomized to either high-dose vitamin D 3 (1.2 million IU over 8 weeks, n=13) versus placebo (n=18), there was no change from baseline to week 8 in hCAP18 mRNA levels in peripheral blood mononuclear cells or in plasma concentrations of LL-37, the protein product of hCAP18.These data suggest that first-line anti-TB drugs may alter the vitamin D-dependent increase in hCAP18 and LL-37 human macrophages.
Crudu, V; Arnadottir, Th; Laticevschi, D
To evaluate practices in initial drug susceptibility testing (DST) in Moldova, anti-tuberculosis drug resistance and the implications for tuberculosis control. Retrospective record review in the national reference laboratory. Of 3463 cases, 57.1% were recorded as 'new' and 24.6% as 'retreatment' cases; previous treatment status was not recorded for 18.3%. Of the 'new' cases, 1655 were correctly classified according to international recommendations and 322 were misclassified. The number of cases increased from 443 in 1995 to 939 in 1999; the proportion of 'retreatment' increased from 17.4% to 35.5%, 'any drug resistance' from 20.3% to 41.6%, and 'multidrug resistance' from 2.7% to 11.2%. In 1998-1999, 'any drug resistance' and 'multidrug resistance' in 800 previously untreated cases were respectively 29.1% and 5.3%, and respectively 61.0% and 21.9% in 521 'retreatment' cases. Of a total of 216 'multidrug-resistant' cases in 1998-1999, 21.8% were reported resistant to ethambutol and 81.5% to streptomycin. Initial specimens for culture are frequently taken late, after the start of treatment, compromising their usefulness for case management or surveillance. Inadequate treatment has led to an increase in the number of cases, the proportion of previously treated cases and the prevalence of drug resistance. In 1998-1999, a high proportion of cases with 'multidrug resistance' were susceptible to ethambutol.
Hoa, N B; Lauritsen, J M; Rieder, H L
-39 kg weight bracket received insufficient dosages. This was almost entirely attributable to patients at the end of the weight bracket. Nevertheless, no significant association was found between treatment failure and death, body weight and insufficient RMP dosage. CONCLUSIONS: Adherence to national...
In making calculations for the purposes of radiation protection, numerical values for parameters used in the calculations are selected. In some cases, data directly applicable to the set of conditions for which the calculations are to be made are unavailable. Therefore, the selection of the values for these parameters may be based on more general data available from the literature or other sources. These values may be referred to as 'default values', that is, values used in default of those based on directly applicable data. The following policy will be applied by Atomic Energy Control Board (AECB) staff in reviewing the radiation protection aspects of submissions associated with licensing, in participating with other organizations in the development of codes and standards, and in any other work which relies to some extent on using default values
Sarkar, Amrita; Javia, Abhay; Pithadia, Pradeep; Parmar, Dipesh
Chronic Obstructive Pulmonary Disease (COPD), a progressive respiratory illness requiring long-term treatment, is a significant cause of morbidity, mortality and economic burden on the family as well as the country. In the tertiary health care facility where the study was carried out, it was observed that many COPD patients did not come for regular follow up. In these patients, treatment interruption may lead to increased morbidity and mortality. This study aimed to find out the reasons for defaulting follow up and treatment in COPD patients. All patients of COPD, attending TB Chest outpatient department during the study period (September 2012 to February 2013), were classified into Group A, B, C, and D according to latest Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines. Data was collected on patient's sociodemographic profile, severity of disease and reasons for defaulting follow up and treatment using pre-tested semi-structured questionnaires, patient history and clinical examination. Data obtained were entered in Microsoft Office Excel 2007 and analysed using Chi-square test. The mean age of the 200 patients recruited was 59.3 years. A total of 87% patients were male. Patients belonging to Group A, B, C and D were 11%, 25.5%, 41.5% and 22% respectively. Overall, 32% patients were defaulters. Three main reasons for default were non-affordability for treatment expenses (39.07%), resolution of symptoms (26.56%), and too ill to come (18.75%). The associations between default rate and demographic variables like age and gender were found statistically significant. Default rate among COPD patients is significantly associated with GOLD Group A and D, patient's income and patient literacy level. Main reasons for default were non-affordability of treatment expenses, too ill to come and resolution of symptoms.
S. N. Shugaeva; E. D. Savilov
The article offers a new method for calculation of incidence of complications after primary anti-tuberculosis vaccination. Using the example of analysis of continuous sampling of complications after anti-tuberculosis vaccination (n = 110) in Irkutsk Region in 2005-2014 the article shows the advantage of the offered method compared to the existing ones.
Mendoza-Ticona, Alberto; Moore, David AJ; Alarcón, Valentina; Samalvides, Frine; Seas, Carlos
Objective To elaborate optimal anti-tuberculosis regimens following drug susceptibility testing (DST) to isoniazid (H) and rifampicin (R). Design 12 311 M. tuberculosis strains (National Health Institute of Peru 2007-2009) were classified in four groups according H and R resistance. In each group the sensitivity to ethambutol (E), pirazinamide (Z), streptomycin (S), kanamycin (Km), capreomycin (Cm), ciprofloxacin (Cfx), ethionamide (Eto), cicloserine (Cs) and p-amino salicilic acid (PAS) was determined. Based on resistance profiles, domestic costs, and following WHO guidelines, we elaborated and selected optimal putative regimens for each group. The potential efficacy (PE) variable was defined as the proportion of strains sensitive to at least three or four drugs for each regimen evaluated. Results Selected regimes with the lowest cost, and highest PE of containing 3 and 4 effective drugs for TB sensitive to H and R were: HRZ (99,5%) and HREZ (99,1%), respectively; RZECfx (PE=98,9%) and RZECfxKm (PE=97,7%) for TB resistant to H; HZECfx (96,8%) and HZECfxKm (95,4%) for TB resistant to R; and EZCfxKmEtoCs (82.9%) for MDR-TB. Conclusion Based on resistance to H and R it was possible to select anti-tuberculosis regimens with high probability of success. This proposal is a feasible alternative to tackle tuberculosis in Peru where the access to rapid DST to H and R is improving progressively. PMID:23949502
Chang, Tien-En; Huang, Yi-Shin; Chang, Chih-Hao; Perng, Chin-Lin; Huang, Yi-Hsiang; Hou, Ming-Chih
Anti-tuberculosis drug-induced liver injury (ATDILI) is a major safety concern in the treatment of tuberculosis (TB). The impact of chronic hepatitis C (CHC) infection on the risk of ATDILI is still controversial. We aimed to assess the influence of CHC infection on ATDILI through a systematic review and meta-analysis. We systemically reviewed all English-language literature in the major medical databases with the subject search terms "anti-tuberculosis drug-induced liver injury" and "anti-tuberculosis drug-induced hepatotoxicity". We then performed a systematic review and meta-analysis of the papers relevant to hepatitis C in qualified publications. A total of 14 studies were eligible for analysis, which included 516 cases with ATDILI and 4301 controls without ATDILI. The pooled odds ratio (OR) of all studies for CHC infection to ATDILI was 3.21 (95% confidence interval (CI): 2.30-4.49). Subgroup analysis revealed that the CHC carriers had a higher risk of ATDILI than those without CHC both in Asians (OR = 2.96, 95% CI: 1.79-4.90) and Caucasians (OR = 4.07, 95% CI: 2.70-6.14), in those receiving standard four combination anti-TB therapy (OR = 2.94, 95% CI: 1.95-4.41) and isoniazid monotherapy (OR = 4.18, 95% CI: 2.36-7.40), in those with a strict definition of DILI (serum alanine aminotransferase [ALT] > 5 upper limit of normal value [ULN], OR = 2.59, 95% CI: 1.58-4.25) and a loose definition of DILI (ALT > 2 or 3 ULN, OR = 4.34, 95% CI: 2.96-6.37), and in prospective studies (OR = 4.16, 95% CI: 2.93-5.90) and case-control studies (OR = 2.43, 95% CI: 1.29-4.58). This meta-analysis suggests that CHC infection may increase the risk of ATDILI. Regular liver tests are mandatory for CHC carriers under anti-TB therapy. Copyright © 2017. Published by Elsevier Taiwan LLC.
Genina, Natalja; Boetker, Johan Peter; Colombo, Stefano
The design and production of an oral dual-compartmental dosage unit (dcDU) was examined in vitro and in vivo with the purpose of physically isolating and modulating the release profile of an anti-tuberculosis drug combination. Rifampicin (RIF) and isoniazid (ISO) are first line combination drugs...... for treatment of tuberculosis (TB) that negatively interact with each other upon simultaneous release in acidic environment. The dcDUs were designed in silico by computer aided design (CAD) and fabricated in two steps; first three-dimensional (3D) printing of the outer structure, followed by hot-melt extrusion...... (HME) of the drug-containing filaments. The structure of the fabricated dcDUs was visualized by scanning electron microscopy (SEM). The 3D printed compartmentalized shells were loaded with filaments containing active pharmaceutical ingredient (API) and selectively sealed to modulate drug dissolution...
As elsewhere in the Western world, between 1900 and 1940 the anti-tuberculosis campaign in the Netherlands produced a wide range of initiatives to promote child health. In each of these the social and the medical were linked, as the hygienic "mood" was encouraged by a child-saving ethos that focused upon the poor. In this article the…
As elsewhere in the Western world, between 1900 and 1940 the anti-tuberculosis campaign in the Netherlands produced a wide range of initiatives to promote child health. In each of these the social and the medical were linked, as the hygienic 'mood' was encouraged by a child-saving ethos that focused
Mycobacterium tuberculosis drug resistance (DR) challenges effective tuberculosis disease control. Current molecular tests examine limited numbers of mutations, and although whole genome sequencing approaches could fully characterise DR, data complexity has restricted their clinical application. A library (1,325 mutations) predictive of DR for 15 anti-tuberculosis drugs was compiled and validated for 11 of them using genomic-phenotypic data from 792 strains. A rapid online ‘TB-Profiler’ tool was developed to report DR and strain-type profiles directly from raw sequences. Using our DR mutation library, in silico diagnostic accuracy was superior to some commercial diagnostics and alternative databases. The library will facilitate sequence-based drug-susceptibility testing.
N. A. Stepanova; E. N. Streltsova; Kh. M. Galimzyanov; B. I. Kantemirova
The article presents the study of frequency of unfavorable side effects to anti-tuberculosis drugs in new pulmonary tuberculosis patients in Regional Clinical TB Dispensary in Astrakhan in 2012-2013. The study reflects the type and nature of unfavorable side effects to specific drugs. It has been found out that side effect occur more often in case of combination of TB drugs compared to one TB drugs. The efficiency of specific therapy in case of side effects has been demonstrated....
Belo, Elsia Nascimento; Orellana, Jesem Douglas Yamall; Levino, Antônio; Basta, Paulo Cesar
To describe the epidemiological situation and the incidence of tuberculosis and to investigate the factors associated with treatment default in the Amazonian municipalities located in the northern Brazilian international border. This retrospective study employed sociodemographic, clinical, and epidemiological tuberculosis data recorded in the Brazilian Notifiable Diseases Information System (SINAN) between 2001 and 2010. Logistic regression was used to identify factors associated with treatment default. Tuberculosis affected mostly indigenous peoples (51.9%), males (57.9%), and people aged 25-44 years (31.4%). The predominant clinical presentation was pulmonary (89.7%), yet in 24.5% of the cases the patients did not undergo sputum smear microscopy, and only half received supervised treatment. In 70.0% of the cases notified, patients were discharged as cured. Treatment default was recorded in 10.0% of the patients. Of all deaths, 4.1% were by tuberculosis and other causes, and 1.7% by multidrug-resistant tuberculosis. The average incidence by race/color was greater among indigenous peoples, ranging from 202.3/100 000 in 2001 to 65.6/100 000 in 2010. Treatment default was associated with failure to perform the follow-up smear at the second, fourth, and sixth months (OR = 11.9, 95%CI: 7.4-19.0); with resuming treatment after default (OR = 3.0, 95%CI: 1.5-5.9); and with living in specific subregions, particularly the Alto Solimões region (OR = 6.7, 95%CI: 4.6-9.8). The present results show a high incidence of tuberculosis in the Amazon portion of the northern Brazilian international border, especially among indigenous peoples. Considering the socio-cultural specificities of these populations and the poor tuberculosis control in this area, the authors of the study conclude that the integration of different national health systems is both necessary and urgent.
Wilcox, Claire E; Claus, Eric D; Calhoun, Vince D; Rachakonda, Srinivas; Littlewood, Rae A; Mickey, Jessica; Arenella, Pamela B; Goodreau, Natalie; Hutchison, Kent E
Identifying predictors of treatment outcome for nicotine use disorders (NUDs) may help improve efficacy of established treatments, like varenicline. Brain reactivity to drug stimuli predicts relapse risk in nicotine and other substance use disorders in some studies. Activity in the default mode network (DMN) is affected by drug cues and other palatable cues, but its clinical significance is unclear. In this study, 143 individuals with NUD (male n = 91, ages 18-55 years) received a functional magnetic resonance imaging scan during a visual cue task during which they were presented with a series of smoking-related or food-related video clips prior to randomization to treatment with varenicline (n = 80) or placebo. Group independent components analysis was utilized to isolate the DMN, and temporal sorting was used to calculate the difference between the DMN blood-oxygen-level dependent signal during smoke cues and that during food cues for each individual. Food cues were associated with greater deactivation compared with smoke cues in the DMN. In correcting for baseline smoking and other clinical variables, which have been shown to be related to treatment outcome in previous work, a less positive Smoke - Food difference score predicted greater smoking at 6 and 12 weeks when both treatment groups were combined (P = 0.005, β = -0.766). An exploratory analysis of executive control and salience networks demonstrated that a more positive Smoke - Food difference score for executive control network predicted a more robust response to varenicline relative to placebo. These findings provide further support to theories that brain reactivity to palatable cues, and in particular in DMN, may have a direct clinical relevance in NUD. © 2017 Society for the Study of Addiction.
Full Text Available Previous studies have focused on resting-state default mode network (DMN alterations in the development and maintenance of depression; however, only a few studies have addressed DMN changes during task-related processing and their results are inconsistent. Therefore, we explored DMN patterns in young adult patients with first-episode, treatment-naïve major depressive disorder (MDD performing an implicit emotional processing task. Patients with MDD (N = 29 and healthy controls (N = 33 were subjected to functional magnetic resonance imaging (fMRI at rest and while performing a gender judgment task. Group independent component analysis (ICA was used to identify DMN component under task state for both groups. The DMN of participants with MDD had decreased functional connectivity in bilateral prefrontal areas compared to controls. Right prefrontal gyrus connectivity for MDD patients correlated negatively with scores on maladaptive scales of the Cognitive Emotion Regulation Questionnaire (CERQ. Our findings suggest that depressed people have altered DMN patterns during implicit emotional processing, which might be related to impaired internal monitoring and emotional regulation ability.
Miwa, S; Suzuki, Y; Shirai, M; Ohba, H; Kanai, M; Eifuku, T; Suda, T; Hayakawa, H; Chida, K
Some patients have adverse reactions to anti-tuberculosis drugs. We have reported that drug lymphocyte stimulation testing (DLST), which we performed at Week 1 of adverse reactions, provides little useful information (14.9% sensitivity). However, it remains unclear whether the time of performance of the DLST contributed to these results. Patients with adverse reactions to anti-tuberculosis drugs, including rash, hepatitis and fever, underwent DLST in the first week of the adverse reaction and were then randomly assigned to Group A (among whom a second DLST was performed 2 months after the reaction) or Group B (among whom a second DLST was performed >12 months after the reaction). We compared Group A with Group B to determine the optimal timing for the performance of DLST. The causative drug was identified by an oral drug provocation test. Consistent with the previous study, the sensitivity of DLST performed in the first week was low (14.3%). For DLST performed later, the sensitivity in Group A and Group B was respectively 5.0% and 6.7%. DLST is not useful for determining the causative drug in patients with rash, hepatitis or fever reactions to anti-tuberculosis drugs, regardless of when it is performed.
Munir, M.K.; Iqbal, R.; Shabbir, I.; Chaudhry, K
Tuberculosis is a major health problem in many parts of the world. Delay in initiation of the treatment may result in prolonged infectious state, drug resistance, relapse and death. Objectives: To determine the factors responsible for not starting tuberculosis treatment among smear positive tuberculosis patients. Study type, settings and duration: This cross sectional study was done at Pakistan Medical Research Council TB Research Center, King Edward Medical University, Lahore, from fifth March 2010 to fifth December 2010. Patients and Methods: Fifty sputum smear positive patients of tuberculosis who did not register themselves in treatment register and presumably did not initiate anti tuberculosis treatment were contacted using telephone or traced by their home addresses. Once contact was established, they were inquired about the reasons for not starting tuberculosis treatment. Results: Of 50 patients 38(76%)belonged to the lower socio economic class and 12(24%) to the lower middle class. Fourteen patients (28%) were illiterate and 23(46%) had only 8 years of education. Of the 50 cases 41(82%) were taking treatment from traditional healers and 4% did not go back to the DOTS program. Physical condition of the patient, social, domestic and religious issues also played some role in default. Conclusions: Lack of health education and poverty were the main factors responsible for non compliance from treatment. Policy message: Sputum testing sites should have a paramedic who should educate the patients about the benefits of treatment and the dangers of default or partial treatment. (author)
Full Text Available OBJECTIVES: To evaluate the incidence, type, severity and predictors of antiretroviral and/or anti-tuberculosis drugs induced liver injury (DILI. METHODS: A total of 1,060 treatment naive patients were prospectively enrolled into four treatment groups: HIV patients receiving efavirenz based HAART alone (Arm-1; TB-HIV co-infected patients with CD4≤200 cells/μL, receiving concomitant rifampicin based anti-TB and efavirenz based HAART (Arm-2; TB-HIV co-infected patients with CD4>200 cells/μL, receiving anti-TB alone (Arm-3; TB patients taking rifampicin based anti-TB alone (Arm-4. Liver enzyme levels were monitored at baseline, 1st, 2nd, 4th, 8th, 12th and 24th weeks during treatment. CD4 and HIV viral load was measured at baseline, 24th and 48th weeks. Data were analyzed using multivariate Cox Proportional Hazards Model. RESULTS: A total of 159 patients (15% developed DILI with severity grades 1, 2, 3 and 4 of 53.5%, 32.7%, 11.3% and 2.5% respectively. The incidence of cholestatic, hepatocellular or mixed pattern was 61%, 15% and 24%, respectively. Incidence of DILI was highest in Arm-2 (24.2%>Arm-3 (10.8%>Arm-1 (8.8%>Arm-4 (2.9%. Concomitant anti-TB-HIV therapy increased the risk of DILI by 10-fold than anti-TB alone (p<0.0001. HIV co-infection increased the risk of anti-TB DILI by 4-fold (p = 0.004. HAART associated DILI was 3-fold higher than anti-TB alone, (p = 0.02. HAART was associated with cholestatic and grade 1 DILI whereas anti-TB therapy was associated with hepatocellular and grade ≥ 2. Treatment type, lower CD4, platelet, hemoglobin, higher serum AST and direct bilirubin levels at baseline were significant DILI predictors. There was no effect of DILI on immunologic recovery or virologic suppression rate of HAART. CONCLUSION: HAART associated DILI is mainly cholestatic and mild whereas hepatocellular or mixed pattern with high severity grade is more common in anti-tuberculosis DILI. TB-HIV co-infection, disease severity
Full Text Available The present study was performed to investigate the effect of bicyclol, a synthetic anti-hepatitis drug with anti-oxidative and anti-inflammatory properties, on anti-tuberculosis (anti-TB drug-induced liver injury and related mechanisms in rats. Bicyclol was given to rats by gavage 2 h before the oral administration of an anti-TB drug once a day for 30 days. Liver injury was evaluated by biochemical and histopathological examinations. Lipid peroxidation, mitochondrial function, and the activity of antioxidants were measured by spectrophotometric methods. Cytokines expression and CYP2E1 activity were determined by ELISA assay and liquid chromatography–tandem mass spectrometry (LC–MS/MS analysis. The expressions of hepatic CYP2E1 and hepatocyte growth factor (HGF were assessed by Western blotting. As a result, bicyclol significantly protected against anti-TB drug-induced liver injury by reducing the elevated serum aminotransferases levels and accumulation of hepatic lipids. Meanwhile, the histopathological changes were also attenuated in rats. The protective effect of bicyclol on anti-TB drug-induced hepatotoxicity was mainly due to its ability to attenuate oxidative stress, suppress the inflammatory cytokines and CYP2E1 expression, up-regulate the expression of HGF, and improve mitochondrial function. Furthermore, administration of bicyclol had no significant effect on the plasma pharmacokinetics of the anti-TB drug in rats.
Aziz, N; Bukhari, M.H; Muneer, M; Tayyab, M; Chaudhry, N.A.
This study was conducted to see the presence of the antimycobacterial antibodies in healthy household contacts of tuberculosis patients and healthy normal subjects who have never been in contact with tuberculosis patients. A total of 200 subjects, 120 with history of household contact and 80 without such history were included in the study. Routine Haematological investigations were performed and all the sera of 200 subjects were tested who 19M, 19G and IgA anti tuberculosis antibodies using ELISA technique. There was no difference in the average age of the household contacts and non-contacts. The complaints of pyrexia, night sweats and loss of weight was more in house hold contacts as compared to non-contacts. The awareness about BCG vaccination was equal among the household contacts and non-contacts. The combined serological positivity of the household contacts was 65.8% and the combined serological positivity for non-contacts was 34.1%. There was no statistically significant difference in the presence of 19M among household contacts as compared to non-contacts. However both IgG and 19A were present in significantly higher number of household contacts as compared to non contacts. This study concludes that the persons living in the house with a patient suffering from active pulmonary tuberculosis (household contact) have more chances of being infected with Mycobacterium tuberculosis as compared to the healthy non-contacts. (author)
O, Hyong-Chol; Wan, Ning
We provide analytical pricing formula of corporate defaultable bond with both expected and unexpected default in the case with stochastic default intensity. In the case with constant short rate and exogenous default recovery using PDE method, we gave some pricing formula of the defaultable bond under the conditions that 1)expected default recovery is the same with unexpected default recovery; 2) default intensity follows one of 3 special cases of Willmott model; 3) default intensity is uncorr...
Full Text Available Reconstruction materials currently used in clinical for osteoarticular tuberculosis (TB are unsatisfactory due to a variety of reasons. Rifampicin (RFP is a well-known and highly effective first-line anti-tuberculosis (anti-TB drug. Poly-DL-lactide (PDLLA and nano-hydroxyapatite (nHA are two promising materials that have been used both for orthopedic reconstruction and as carriers for drug release. In this study we report the development of a novel anti-TB implant for osteoarticular TB reconstruction using a combination of RFP, PDLLA and nHA.RFP, PDLLA and nHA were used as starting materials to produce a novel anti-TB activity implant by the solvent evaporation method. After manufacture, the implant was characterized and its biodegradation and drug release profile were tested. The in vitro cytotoxicity of the implant was also evaluated in pre-osteoblast MC3T3-E1 cells using multiple methodologies.A RFP/PDLLA/nHA composite was successfully synthesized using the solvent evaporation method. The composite has a loose and porous structure with evenly distributed pores. The production process was steady and no chemical reaction occurred as proved by Fourier Transform Infrared Spectroscopy (FTIR and X-Ray Diffraction (XRD. Meanwhile, the composite blocks degraded and released drug for at least 12 weeks. Evaluation of in vitro cytotoxicity in MC3T3-E1 cells verified that the synthesized composite blocks did not affect cell growth and proliferation.It is feasible to manufacture a novel bioactive anti-TB RFP/PDLLA/nHA composite by the solvent evaporation method. The composite blocks showed appropriate properties such as degradation, drug release and biosafety to MC3T3-E1 cells. In conclusion, the novel composite blocks may have great potential for clinical applications in repairing bone defects caused by osteoarticular TB.
Chauvet, Marcelle; Gabriel, Stuart; Lutz, Chandler
We use Google search query data to develop a broad-based and real-time index of mortgage default risk. Unlike established indicators, our Mortgage Default Risk Index (MDRI) directly reflects households’concerns regarding their risk of mortgage default. The MDRI predicts housing returns, mortgage ...... delinquency indicators, and subprime credit default swaps. These results persist both in- and out-of-sample and at multiple data frequencies. Together, research findings suggest internet search queries yield valuable new insights into household mortgage default risk.......We use Google search query data to develop a broad-based and real-time index of mortgage default risk. Unlike established indicators, our Mortgage Default Risk Index (MDRI) directly reflects households’concerns regarding their risk of mortgage default. The MDRI predicts housing returns, mortgage...
Full Text Available BACKGROUND: Long-term exposure to anti-tuberculosis medication increases risk of adverse drug reactions and toxicity. The objective of this investigation was to determine factors associated with anti-tuberculosis adverse drug reactions in Lima, Peru, with special emphasis on MDR-TB medication, HIV infection, diabetes, age and tobacco use. METHODOLOGY AND RESULTS: A case-control study was performed using information from Peruvian TB Programme. A case was defined as having reported an anti-TB adverse drug reaction during 2005-2010 with appropriate notification on clinical records. Controls were defined as not having reported a side effect, receiving anti-TB therapy during the same time that the case had appeared. Crude, and age- and sex-adjusted models were calculated using odds ratios (OR and 95% confidence intervals (95%CI. A multivariable model was created to look for independent factors associated with side effect from anti-TB therapy. A total of 720 patients (144 cases and 576 controls were analyzed. In our multivariable model, age, especially those over 40 years (OR = 3.93; 95%CI: 1.65-9.35, overweight/obesity (OR = 2.13; 95%CI: 1.17-3.89, anemia (OR = 2.10; IC95%: 1.13-3.92, MDR-TB medication (OR = 11.1; 95%CI: 6.29-19.6, and smoking (OR = 2.00; 95%CI: 1.03-3.87 were independently associated with adverse drug reactions. CONCLUSIONS: Old age, anemia, MDR-TB medication, overweight/obesity status, and smoking history are independent risk factors associated with anti-tuberculosis adverse drug reactions. Patients with these risk factors should be monitored during the anti-TB therapy. A comprehensive clinical history and additional medical exams, including hematocrit and HIV-ELISA, might be useful to identify these patients.
Lee, Mei Lin; Hassali, Mohamed Azmi; Shafie, Asrul Akmal
Treatment default among the smokers hinders the effectiveness of the delivery of cessation services. While many studies have predicted the defaulters' characteristics, the reasons why these smokers dropped out and continued smoking are seldom explored. This study examined the barriers encountered by such smokers and their respective health care providers (HCPs) in relation to the discontinuation of cessation treatment. From May 2010 to March 2011, 15 current adult smokers and 9 HCPs from 2 Quit Smoking Clinics (QSCs) in the Melaka Tengah District, Malacca, Malaysia were interviewed on smoking, cessation, and the QSC. Interviews were audio recorded and transcribed verbatim. The transcripts were subsequently translated into English and analyzed using thematic analysis. The barriers encountered were categorized as Individual- and Clinic-level. Both smokers and HCPs acknowledged that the smokers' low intrinsic motivation was the individual-level barrier. The clinic-level barriers were the mismatched perceptions of smokers and HCPs regarding the HCPs' roles, skills, and attitudes, as well as the availability and efficacy of smoking cessation aids (SCAs). While the smokers viewed the program as not helpful, the HCPs cited the lack of organizational support as their main barrier. The reasons for treatment default centered on the overall dissatisfaction with the treatment (due to the program, HCP, and SCA factors) combined with the smokers' low intrinsic motivation. Optimizing the interplay of the extrinsic motivational cues, such as the HCP and SCA factors, would complement the smoker's low intrinsic motivation and thus encourage treatment retention. However, it is necessary to strike a balance between the individual smoker's needs and the availability of organizational support. Copyright © 2013 Elsevier Inc. All rights reserved.
Genina, Natalja; Boetker, Johan Peter; Colombo, Stefano; Harmankaya, Necati; Rantanen, Jukka; Bohr, Adam
The design and production of an oral dual-compartmental dosage unit (dcDU) was examined in vitro and in vivo with the purpose of physically isolating and modulating the release profile of an anti-tuberculosis drug combination. Rifampicin (RIF) and isoniazid (ISO) are first line combination drugs for treatment of tuberculosis (TB) that negatively interact with each other upon simultaneous release in acidic environment. The dcDUs were designed in silico by computer aided design (CAD) and fabricated in two steps; first three-dimensional (3D) printing of the outer structure, followed by hot-melt extrusion (HME) of the drug-containing filaments. The structure of the fabricated dcDUs was visualized by scanning electron microscopy (SEM). The 3D printed compartmentalized shells were loaded with filaments containing active pharmaceutical ingredient (API) and selectively sealed to modulate drug dissolution. The drug release profile of the dcDUs was characterized by pH-transfer dissolution in vitro and pharmacokinetics studies in rats, and resulted in modified release of the APIs from the dcDUs as compared to the free filaments. Furthermore, the selective physical sealing of the compartments resulted in an effective retardation of the in vitro API release. The findings of this study support the development of controllable-by-design dcDU systems for combination therapies to enable efficient therapeutic translation of oral dosage forms. Copyright © 2017 Elsevier B.V. All rights reserved.
Mohamed N. Abdelghani
Full Text Available The paper deals with defaultable markets, one of the main research areas of mathematical finance. It proposes a new approach to the theory of such markets using techniques from the calculus of optional stochastic processes on unusual probability spaces, which was not presented before. The paper is a foundation paper and contains a number of fundamental results on modeling of defaultable markets, pricing and hedging of defaultable claims and results on the probability of default under such conditions. Moreover, several important examples are presented: a new pricing formula for a defaultable bond and a new pricing formula for credit default swap. Furthermore, some results on the absence of arbitrage for markets on unusual probability spaces and markets with default are also provided.
Liew, S M; Khoo, E M; Ho, B K; Lee, Y K; Mimi, O; Fazlina, M Y; Asmah, R; Lee, W K; Harmy, M Y; Chinna, K; Jiloris, F D
To determine treatment outcomes and associated predictors of all patients registered in 2012 with the Malaysian National Tuberculosis (TB) Surveillance Registry. Sociodemographic and clinical data were analysed. Unfavourable outcomes included treatment failure, transferred out and lost to follow-up, treatment defaulters, those not evaluated and all-cause mortality. In total, 21 582 patients were registered. The mean age was 42.36 ± 17.77 years, and 14.2% were non-Malaysians. The majority were new cases (93.6%). One fifth (21.5%) had unfavourable outcomes; of these, 46% died, 49% transferred out or defaulted and 1% failed treatment. Predictors of unfavourable outcomes were older age, male sex, foreign citizenship, lower education, no bacille Calmette-Guérin (BCG) vaccination scar, treatment in tertiary settings, smoking, previous anti-tuberculosis treatment, human immunodeficiency virus infection, not receiving directly observed treatment, advanced chest radiography findings, multidrug-resistant TB (MDR-TB) and extra-pulmonary TB. For all-cause mortality, predictors were similar except for rural dwelling and nationality (higher mortality among locals). Absence of BCG scar, previous treatment for TB and MDR-TB were not found to be predictors of all-cause mortality. Indigenous populations in East Malaysia had lower rates of unfavourable treatment outcomes. One fifth of TB patients had unfavourable outcomes. Intervention strategies should target those at increased risk of unfavourable outcomes and all-cause mortality.
Full Text Available INTRODUCTION: Functional magnetic resonance imaging studies enable the investigation of neural correlates underlying behavioral performance. We investigate the effect of active and sham Continuous Positive Airway Pressure (CPAP treatment on working memory function of patients with Obstructive Sleep Apnea Syndrome (OSAS considering Task Positive and Default Mode networks (TPN and DMN. METHODS: An experiment with 4 levels of visuospatial n-back task was used to investigate the pattern of cortical activation in 17 men with moderate or severe OSAS before and after 2 months of therapeutic (active or sub-therapeutic (sham CPAP treatment. RESULTS: Patients with untreated OSAS had significantly less deactivation in the temporal regions of the DMN as compared to healthy controls, but activation within TPN regions was comparatively relatively preserved. After 2 months of treatment, active and sham CPAP groups exhibited opposite trends of cerebral activation and deactivation. After treatment, the active CPAP group demonstrated an increase of cerebral activation in the TPN at all task levels and of task-related cerebral deactivation in the anterior midline and medial temporal regions of the DMN at the 3-back level, associated with a significant improvement of behavioral performance, whereas the sham CPAP group exhibited less deactivation in the temporal regions of Default Mode Network and less Task Positive Network activation associated to longer response times at the 3-back. CONCLUSION: OSAS has a significant negative impact primarily on task-related DMN deactivation, particularly in the medial temporal regions, possibly due to nocturnal hypoxemia, as well as TPN activation, particularly in the right ventral fronto-parietal network. After 2 months of active nasal CPAP treatment a positive response was noted in both TPN and DMN but without compete recovery of existing behavioral and neuronal deficits. Initiation of CPAP treatment early in the course of the
Rijken, H.A.; Altman, E.I.
We propose a new approach toward assessing sovereign risk by examining rigorously the health and aggregate default risk of a nation's private corporate sector. Models can be utilised to measure the probability of default of the non-financial sector cumulatively for five years, both as an absolute
The focus of this article is the history of Canada's reception of Bacillus Calmette-Guerin (BCG), an anti-tuberculosis vaccine which has almost constantly been plagued with controversy. The article examines this vaccine NRCC sponsored introduction in 1925, which led to the creation of the Associate Committee on Tuberculosis Research, a committee almost unique for its acrimonious debates. It also analyzes the interests at stakes in the ultimate rejection of the BCG by the federal Department of Agriculture veterinary services and, with the exception of Quebec and Newfoundland, by almost all public health authorities in Canada. Based on sources never taped before, this paper sheds a light on the multiple ramifications of a little known episode of the Canadian public health history.
Grzelak, Edyta M; Hwang, Changhwa; Cai, Geping; Nam, Joo-Won; Choules, Mary P; Gao, Wei; Lankin, David C; McAlpine, James B; Mulugeta, Surafel G; Napolitano, José G; Suh, Joo-Won; Yang, Seung Hwan; Cheng, Jinhua; Lee, Hanki; Kim, Jin-Yong; Cho, Sang-Hyun; Pauli, Guido F; Franzblau, Scott G; Jaki, Birgit U
While natural products constitute an established source of lead compounds, the classical iterative bioassay-guided isolation process is both time- and labor-intensive and prone to failing to identify active minor constituents. (HP)TLC-bioautography-MS/NMR, which combines cutting-edge microbiological, chromatographic, and spectrometric technologies, was developed to accelerate anti-tuberculosis (TB) drug discovery from natural sources by acquiring structural information at a very early stage of the isolation process. Using the avirulent, bioluminescent Mtb strain mc 2 7000 luxABCDE, three variations of bioautography were evaluated and optimized for sensitivity in detecting anti-TB agents, including established clinical agents and new leads with novel mechanisms of action. Several exemplary applications of this approach to microbial extracts demonstrate its potential as a routine method in anti-TB drug discovery from natural sources.
Abstract Background Combating the spread of drug resistant tuberculosis is a global health priority. Whole genome association studies are being applied to identify genetic determinants of resistance to anti-tuberculosis drugs. Protein structure and interaction modelling are used to understand the functional effects of putative mutations and provide insight into the molecular mechanisms leading to resistance. Methods To investigate the potential utility of these approaches, we analysed the genomes of 144 Mycobacterium tuberculosis clinical isolates from The Special Programme for Research and Training in Tropical Diseases (TDR) collection sourced from 20 countries in four continents. A genome-wide approach was applied to 127 isolates to identify polymorphisms associated with minimum inhibitory concentrations for first-line anti-tuberculosis drugs. In addition, the effect of identified candidate mutations on protein stability and interactions was assessed quantitatively with well-established computational methods. Results The analysis revealed that mutations in the genes rpoB (rifampicin), katG (isoniazid), inhA-promoter (isoniazid), rpsL (streptomycin) and embB (ethambutol) were responsible for the majority of resistance observed. A subset of the mutations identified in rpoB and katG were predicted to affect protein stability. Further, a strong direct correlation was observed between the minimum inhibitory concentration values and the distance of the mutated residues in the three-dimensional structures of rpoB and katG to their respective drugs binding sites. Conclusions Using the TDR resource, we demonstrate the usefulness of whole genome association and convergent evolution approaches to detect known and potentially novel mutations associated with drug resistance. Further, protein structural modelling could provide a means of predicting the impact of polymorphisms on drug efficacy in the absence of phenotypic data. These approaches could ultimately lead to novel
Background Combating the spread of drug resistant tuberculosis is a global health priority. Whole genome association studies are being applied to identify genetic determinants of resistance to anti-tuberculosis drugs. Protein structure and interaction modelling are used to understand the functional effects of putative mutations and provide insight into the molecular mechanisms leading to resistance. Methods To investigate the potential utility of these approaches, we analysed the genomes of 144 Mycobacterium tuberculosis clinical isolates from The Special Programme for Research and Training in Tropical Diseases (TDR) collection sourced from 20 countries in four continents. A genome-wide approach was applied to 127 isolates to identify polymorphisms associated with minimum inhibitory concentrations for first-line anti-tuberculosis drugs. In addition, the effect of identified candidate mutations on protein stability and interactions was assessed quantitatively with well-established computational methods. Results The analysis revealed that mutations in the genes rpoB (rifampicin), katG (isoniazid), inhA-promoter (isoniazid), rpsL (streptomycin) and embB (ethambutol) were responsible for the majority of resistance observed. A subset of the mutations identified in rpoB and katG were predicted to affect protein stability. Further, a strong direct correlation was observed between the minimum inhibitory concentration values and the distance of the mutated residues in the three-dimensional structures of rpoB and katG to their respective drugs binding sites. Conclusions Using the TDR resource, we demonstrate the usefulness of whole genome association and convergent evolution approaches to detect known and potentially novel mutations associated with drug resistance. Further, protein structural modelling could provide a means of predicting the impact of polymorphisms on drug efficacy in the absence of phenotypic data. These approaches could ultimately lead to novel resistance
Kolovski, Vladimir; Parsia, Bijan; Katz, Yarden
...) have often requested some form of non-monotonic reasoning. In this paper, we present preliminary optimizations and an implementation of a restricted version of Reiter's default logic as an extension to the description logic fragment of OWL, OWL DL...
Svetlana Andrianova; Badi H Baltagi; Panicos O Demetriades
African financial deepening is beset by a high rate of loan defaults, which encourages banks to hold liquid assets instead of lending. We put forward a novel theoretical model that captures the salient features of African credit markets which shows that equilibrium with high loan defaults and low lending can arise when contract enforcement institutions are weak, investment opportunities are relatively scarce and information imperfections abound. We provide evidence using a panel of 110 banks ...
Full Text Available Yingchan Wang,1 Weijun Tang,2 Xiaoduo Fan,3 Jianye Zhang,1 Daoying Geng,2 Kaida Jiang,1 Dianming Zhu,1 Zhenhua Song,1 Zeping Xiao,1 Dengtang Liu1 1First-Episode Schizophrenia and Early Psychosis Program, Division of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, 2Department of Radiology, Huashan Hospital, Fu Dan University, Shanghai, People’s Republic of China; 3Psychotic Disorders Program, UMass Memorial Medical Center, UMass Medical School, Worcester, MA, USA Objective: Abnormal resting-state functional connectivity (FC, particularly in the default mode network (DMN and the salience network (SN, has been reported in schizophrenia, but little is known about the effects of antipsychotics on these networks. The purpose of this study was to examine the effects of atypical antipsychotics on DMN and SN and the relationship between these effects and symptom improvement in patients with schizophrenia.Methods: This was a prospective study of 33 patients diagnosed with schizophrenia and treated with antipsychotics at Shanghai Mental Health Center. Thirty-three healthy controls matched for age and gender were recruited. All subjects underwent functional magnetic resonance imaging (fMRI. Healthy controls were scanned only once; patients were scanned before and after 6–8 weeks of treatment.Results: In the DMN, the patients exhibited increased FC after treatment in the right superior temporal gyrus, right medial frontal gyrus, and left superior frontal gyrus and decreased FC in the right posterior cingulate/precuneus (P<0.005. In the SN, the patients exhibited decreased FC in the right cerebellum anterior lobe and left insula (P<0.005. The FC in the right posterior cingulate/precuneus in the DMN negatively correlated with the difference between the Clinical Global Impression (CGI score pre/post-treatment (r=–0.564, P=0.023 and negative trends with the difference in the Positive and Negative
Full Text Available The mechanism of anti-tuberculosis immunity drew the attention of scientists since the established of the infectious nature of tuberculosis. The famous ukrainian microbiologist and immunologist M.M. Tsehnovitser in period from 1921 to 1940 years spent a lot of original experiments for elucidation of the role of allergy in the anti-tuberculosis immunity. M.M. Tsehnovitser believed that a common cause of infectious allergy is tuberculosis granuloma, which even at rest eliminated weakened microbes and their products in general lymphatic and blood stream of the body. In his experiments M.M. Tsehnovitser discovered: 1 When the body comes in contact with M.tuberculosisi formed tuberculosis centre. Infection meets local tissue reaction and in incubation period formed sensitization. In this state the body manifested as a natural susceptibility and resistance to infection. During this period organism going through the initial stage of allergy. 2. Meanwhile, the infectious process goes on and the M.tuberculosisi giving rise. The body reacts to this change in the formula blood - leukocytosis, monocytosis, eosinophilia. Tuberculosis focus represents a formed granuloma. This phase of tuberculosis infection accompanied by severe allergy. 3. Then there are two versions of the process. In the first case happened the generalization of tuberculosis infection. The blood reacts are leukopenia, monocytosis, eosinophilia and lymphocytosis due to toxic processes. In the second case M.tuberculosi multiplied only local in the granuloma and is not generalization of tuberculosis process. In this case, natural immunity is raised. There are allergy and positive anergy in later. 4. It is exclusively unique phenomenon for tuberculous process is the regression of the fire with his sterilization. This type of tuberculous process is in BCG-infection. In the source of infection observed complete resolution of pathological tissue, blood initially reacts slightly, but quickly comes
Tregellas, Jason R; Wylie, Korey P; Rojas, Donald C; Tanabe, Jody; Martin, Jesse; Kronberg, Eugene; Cordes, Dietmar; Cornier, Marc-Andre
The regulation of energy intake is a complex process involving the integration of homeostatic signals and both internal and external sensory inputs. To better understand the neurobiology of this process and how it may be dysfunctional in obesity, this study examined activity of the brain's "default network" in reduced-obese (RO) as compared to lean individuals. The default network is a group of functionally connected brain regions thought to play an important role in internally directed cognitive activity and the interplay between external and internal sensory processing. Functional magnetic resonance imaging was performed in 24 lean and 18 RO individuals in the fasted state after 2 days of eucaloric energy intake and after 2 days of 30% overfeeding in a counterbalanced design. Scanning was performed while subjects passively viewed images of food and nonfood objects. Independent component analysis was used to identify the default network component. In the eucaloric state, greater default network activity was observed in RO compared to lean individuals in the lateral inferior parietal and posterior cingulate cortices. Activity was positively correlated with appetite. Overfeeding resulted in increased default network activity in lean but not RO individuals. These findings suggest that the function of the default network, a major contributor to intrinsic neuronal activity, is altered in obesity and/or obese-prone individuals. Future studies of the network's function and its relationship to other brain networks may improve our understanding of the mechanisms and treatment of obesity.
Full Text Available The pathogenic mechanism of anti-tuberculosis (anti-TB drug-induced hepatitis is associated with drug metabolizing enzymes. No tagging single-nucleotide polymorphisms (tSNPs of cytochrome P450 2E1(CYP2E1 in the risk of anti-TB drug-induced hepatitis have been reported. The present study was aimed at exploring the role of tSNPs in CYP2E1 gene in a population-based anti-TB treatment cohort.A nested case-control study was designed. Each hepatitis case was 14 matched with controls by age, gender, treatment history, disease severity and drug dosage. The tSNPs were selected by using Haploview 4.2 based on the HapMap database of Han Chinese in Beijing, and detected by using TaqMan allelic discrimination technology.Eighty-nine anti-TB drug-induced hepatitis cases and 356 controls were included in this study. 6 tSNPs (rs2031920, rs2070672, rs915908, rs8192775, rs2515641, rs2515644 were genotyped and minor allele frequencies of these tSNPs were 21.9%, 23.0%, 19.1%, 23.6%, 20.8% and 44.4% in the cases and 20.9%, 22.7%, 18.9%, 23.2%, 18.2% and 43.2% in the controls, respectively. No significant difference was observed in genotypes or allele frequencies of the 6 tSNPs between case group and control group, and neither of haplotypes in block 1 nor in block 2 was significantly associated with the development of hepatitis.Based on the Chinese anti-TB treatment cohort, we did not find a statistically significant association between genetic polymorphisms of CYP2E1 and the risk of anti-TB drug-induced hepatitis. None of the haplotypes showed a significant association with the development of hepatitis in Chinese TB population.
Ghafoor, T.; Ikram, A.; Abbasi, S. A.; Zaman, G.; Ayyub, M.; Palomino, J. C.; Vandamme, P.; Martin, A.
Objective:To determine the current sensitivity pattern of second line anti-tuberculosis drugs against clinical isolates of Multidrug Resistant Mycobacterium tuberculosis (MDR-TB). Study Design: A cross-sectional study. Place and Duration of Study: Department of Microbiology, Armed Forces Institute of Pathology (AFIP), Rawalpindi, from November 2011 to April 2013. Methodology: Samples received during the study period were processed on BACTEC MGIT 960 system for Mycobacterium tuberculosis (MTB) culture followed by first line drugs susceptibility testing of culture proven MTB isolates. On the basis of resistance to rifampicin and isoniazid, 100 clinical isolates of MDR-TB were further subjected to susceptibility testing against amikacin (AMK), capreomycin (CAP), ofloxacin (OFL) and ethionamide (ETH) as per standard BACTEC MGIT 960 instructions. Results: Out of 100 MDR-TB isolates, 62% were from male patients and 38% from female patients. 97% were sensitive to AMK, 53% to OFL, 87% to CAP; and 87% were sensitive to ETH. Conclusion: The majority of the MDR-TB isolates showed excellent sensitivity against AMK, CAP and ETH. However, sensitivity of MDR-TB isolates against fluoroquinolones like OFL was not encouraging. (author)
course (DOTS) strategies, there is still a high prevalence of TB and a high treatment interruption rate in rural South Africa. Methods: The ... sectional study in which data were collected from 15 July 2004 to 15 January 2005 from patients who were on TB treatment and ..... support in the self care behaviors of diabetics. Psychol ...
University College Hospital, a tertiary healthcare center located in Ibadan, Nigeria. It was a prospective observational study of patients aged between 18 and. 65 years. The study took place when TB-HIV treatment allowed for treatment of TB alone before commencement of anti-retroviral therapy, thus it was possible to ...
Sunstein, Cass R.; Reisch, Lucia A.
. The underlying reasons include the power of suggestion; inertia and procrastination; and loss aversion. If well-chosen, climate-friendly defaults are likely to have large effects in reducing the economic and environmental harms associated with various products and activities. In deciding whether to establish...
Sunstein, Cass R.; Reisch, Lucia
The article offers information on the two sources of energy including green energy and gray energy. It discusses several facts which includes lower levels of greenhouse gases and conventional pollutants, relationship between economic incentives and underlying preferences and potential effects of ...... of green default rules.....
Klompjan, R.; Wouters, Marc
Understanding default risk in project finance is relevant to investors. This article investigates which factors are most strongly associated with the occurrence of project finance default, using data from 210 projects, of which 37 were in default. The authors found that the use of proven technology,
... 24 Housing and Urban Development 2 2010-04-01 2010-04-01 false Default. 320.15 Section 320.15... SECURITIES Pass-Through Type Securities § 320.15 Default. (a) Issuer default. Any failure or inability of the... default of the issuer. (b) Action upon default. Upon any default by the issuer, the Association may: (1...
Carrigy, Nicholas B; Chang, Rachel Y; Leung, Sharon S Y; Harrison, Melissa; Petrova, Zaritza; Pope, Welkin H; Hatfull, Graham F; Britton, Warwick J; Chan, Hak-Kim; Sauvageau, Dominic; Finlay, Warren H; Vehring, Reinhard
To compare titer reduction and delivery rate of active anti-tuberculosis bacteriophage (phage) D29 with three inhalation devices. Phage D29 lysate was amplified to a titer of 11.8 ± 0.3 log 10 (pfu/mL) and diluted 1:100 in isotonic saline. Filters captured the aerosolized saline D29 preparation emitted from three types of inhalation devices: 1) vibrating mesh nebulizer; 2) jet nebulizer; 3) soft mist inhaler. Full-plate plaque assays, performed in triplicate at multiple dilution levels with the surrogate host Mycobacterium smegmatis, were used to quantify phage titer. Respective titer reductions for the vibrating mesh nebulizer, jet nebulizer, and soft mist inhaler were 0.4 ± 0.1, 3.7 ± 0.1, and 0.6 ± 0.3 log 10 (pfu/mL). Active phage delivery rate was significantly greater (p pfu/min) than for the jet nebulizer (5.4x10 4 ± 1.3x10 4 pfu/min). The soft mist inhaler delivered 4.6x10 6 ± 2.0x10 6 pfu per 11.6 ± 1.6 μL ex-actuator dose. Delivering active phage requires a prudent choice of inhalation device. The jet nebulizer was not a good choice for aerosolizing phage D29 under the tested conditions, due to substantial titer reduction likely occurring during droplet production. The vibrating mesh nebulizer is recommended for animal inhalation studies requiring large amounts of D29 aerosol, whereas the soft mist inhaler may be useful for self-administration of D29 aerosol.
Zhu, Xueling; Wang, Xiang; Xiao, Jin; Liao, Jian; Zhong, Mingtian; Wang, Wei; Yao, Shuqiao
Imaging studies have shown that major depressive disorder (MDD) is associated with altered activity patterns of the default mode network (DMN). However, the neural correlates of the resting-state DMN and MDD-related pathopsychological characteristics, such as depressive rumination and overgeneral autobiographical memory (OGM) phenomena, still remain unclear. Using independent component analysis, we analyzed resting-state functional magnetic resonance imaging data obtained from 35 first-episode, treatment-naive young adults with MDD and from 35 matched healthy control subjects. Patients with MDD exhibited higher levels of rumination and OGM than did the control subjects. We observed increased functional connectivity in the anterior medial cortex regions (especially the medial prefrontal cortex and anterior cingulate cortex) and decreased functional connectivity in the posterior medial cortex regions (especially the posterior cingulate cortex/precuneus) in MDD patients compared with control subjects. In the depressed group, the increased functional connectivity in the anterior medial cortex correlated positively with rumination score, while the decreased functional connectivity in the posterior medial cortex correlated negatively with OGM score. We report dissociation between anterior and posterior functional connectivity in resting-state DMNs of first-episode, treatment-naive young adults with MDD. Increased functional connectivity in anterior medial regions of the resting-state DMN was associated with rumination, whereas decreased functional connectivity in posterior medial regions was associated with OGM. These results provide new evidence for the importance of the DMN in the pathophysiology of MDD and suggest that abnormal DMN activity may be an MDD trait. Copyright Â© 2012 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
Chiang, Chen-Yuan; Yu, Ming-Chih; Shih, Hsiu-Chen; Yen, Muh-Yong; Hsu, Yu-Ling; Yang, Shiang-Lin; Lin, Tao-Ping; Bai, Kuan-Jen
It was reported that 35.5% of tuberculosis (TB) cases reported in 2003 in Taipei City had no recorded pre-treatment body weight and that among those who had, inconsistent dosing of anti-TB drugs was frequent. Taiwan Centers for Disease Control (CDC) have taken actions to strengthen dosing of anti-TB drugs among general practitioners. Prescribing practices of anti-TB drugs in Taipei City in 2007-2010 were investigated to assess whether interventions on dosing were effective. Lists of all notified culture positive TB cases in 2007-2010 were obtained from National TB Registry at Taiwan CDC. A medical audit of TB case management files was performed to collect pretreatment body weight and regimens prescribed at commencement of treatment. Dosages prescribed were compared with dosages recommended. The proportion of patients with recorded pre-treatment body weight was 64.5% in 2003, which increased to 96.5% in 2007-2010 (pTaipei City has remarkably improved after health authorities implemented a series of interventions.
Seventeen (38.6%) patients dropped out of treatment, before, during or after completing NAC. Ten of these defaulted due to inadequate funds to procure chemotherapy, three patients because they insisted on immediate mastectomy, and four of these patients refused surgery when they achieved complete clinical response, ...
Full Text Available Introduction: The identification and characterization of two M. tuberculosis-specific antigens (ESAT-6 and CFP- 10 has led to the development of a whole blood new generation of M. tuberculosis specific diagnostic tests, that have several advantages over tuberculin skin test (TST, in terms of higher specificity, better correlation with surrogate measures of exposure to M. tuberculosis in low-incidence setting, and less cross-reactivity with M. bovis (BCG vaccine and environmental mycobacteria.The role of these new tests in evaluating post-therapy tuberculosis eradication has not been investigated yet. Aim of this longitudinal study was to determinate changes of response to M. tuberculosis-specific antigens in patients during the standard tuberculosis treatment and to investigate the in vitro effects of tuberculosis drugs on the IFN-γ release. Methods: 23 individuals with active tuberculosis were enrolled and followed over time.They were tested with QuantiFERON TB-Gold (QFT-Gold at four time points: at diagnosis (t0, after 3 and 6 months of treatment (t1- t2 and at the end of the specific treatment (t3. Results: At baseline all patients were positive by QFT-Gold.At second time-point 17 out of 23 (74% were positive, at third time-point 11 of 23 (47% were positive, at treatment completion 3/23 (13% were positive.The conversion to negative response to M. tuberculosis-specific antigens was found in 87% patients analyzed after successful therapy. Longitudinal QFT-Gold testing shown a significant decrease (p<0.001 of IFN-γ response during the therapy. No inhibitory effect on IFN-γ release was noted in vitro for chemotherapy using at concentrations compatible with those achieved in serum of treated patients.We have revealed an inhibitory effect only at concentrations 2-3 times greater than those previously tested. Conclusion: A successful therapy for tuberculosis causes a significant decrease of the ESAT-6 and CFP-10 response and this data suggest
Background Drug resistance has been a cause of concern for tuberculosis (TB) control in both developed and developing countries. Careful monitoring of the patterns and trends of drug resistance should remain a priority. Methods Strains were collected from 1824 diagnosed sputum smear positive pulmonary TB patients in Jiangsu province of China and then tested for drug susceptibility against rifampicin, isoniazid, ethambutol and streptomycin. The prevalence and patterns of drug resistance in mycobacterium tuberculosis (MTB) isolates were investigated. Multiple logistic regression analysis was performed to identify the risk factors for multidrug resistant (MDR) bacterial infection. The strength of association was estimated by odds ratio (OR) and 95% confidence interval (95% CI). Results The drug susceptibility tests showed that 1077(59.05%) MTB strains were sensitive to all the four antibiotics and the other 747(40.95%) strains were resistant to at least one drug. The proportions of mono-drug resistance were 28.73% for isoniazid, 19.41% for rifampicin, 29.33% for streptomycin, and 13.98% for ethambutol, respectively. The prevalence of MDR-TB was 16.61%, which was significantly different between new cases (7.63%) and those with previous treatment history (33.07%). Geographical variation of drug resistance was observed, where the proportion of MDR-TB among new cases was higher in the central (9.50%) or north part (9.57%) than that in the south area (4.91%) of Jiangsu province. The age of patients was significantly associated with the risk of drug resistance (P control. Prevention and control of drug-resistant TB should be emphasized by the revised DOTS (direct observed therapy, short course) program through prompt case detection, routine and quality-assured drug susceptibility test for patients at high risk of resistance, programmatic treatment with both first and second-line medicines, and systematic treatment observation, with priority for high MDR-TB settings. PMID
Full Text Available Tuberculosis is a major problem in public health. While new effective treatments to combat the disease are currently under development, they tend suffer from poor solubility often resulting in low and/or inconsistent oral bioavailability. Mesoporous materials are here investigated in an in vitro intracellular assay, for the effective delivery of compound PA-824; a poorly soluble bactericidal agent being developed against Tuberculosis (TB. Mesoporous materials enhance the solubility of PA-824; however, this is not translated into a higher antibacterial activity in TB-infected macrophages after 5 days of incubation, where similar values are obtained. The lack of improved activity may be due to insufficient release of the drug from the mesopores in the context of the cellular environment. However, these results show promising data for the use of mesoporous particles in the context of oral delivery with expected improvements in bioavailability.
Imperiale, Belén R; Cataldi, Ángel A; Morcillo, Nora S
Latent tuberculosis has been associated with the persistence of dormant Mycobacterium tuberculosis in the organism of infected individuals, who are reservoirs of the bacilli and the source for spreading the disease in the community. New active anti-TB drugs exerting their metabolic action at different stages and on latent/dormant bacilli are urgently required to avoid endogenous reactivations and to be part of treatments of multi- and extensively-drug resistant tuberculosis (M/XDR-TB). It was previously reported that azole drugs are active against M. tuberculosis. For that reason, the aims of this study were to determine the in vitro activity of azole drugs, imidazole (clotrimazole, CLO and econazole, ECO) and nitroimidazole (metronidazole, MZ and ipronidazole, IPZ), against a collection of MDR M. tuberculosis clinical isolates; and to analyze their potential use in both the LTB and the active forms of M/XDR-TB treatments. A total of 55 MDR M. tuberculosis isolates and H37Rv were included. MZ and IPZ activity against M. tuberculosis isolates were tested using anaerobic culture conditions. The activity of ECO and CLO was measured by the minimal inhibitory concentration (MIC) using a microdilution colorimetric method. MZ and IPZ showed bacteriostatic activity against M. tuberculosis strains. MIC 50 and MIC 90 to ECO was 4.0μg/ml, while MIC 50 to CLO was 4.0μg/ml and MIC 90 was 8.0μg/ml respectively. All azole compounds tested in the study showed inhibitory activity against MDR M. tuberculosis clinical isolates. Copyright © 2017 Asociación Argentina de Microbiología. Publicado por Elsevier España, S.L.U. All rights reserved.
Full Text Available China has a high burden of drug-resistant tuberculosis (TB. As irrational use and inadequate dosing of anti-TB drugs may contribute to the epidemic of drug-resistant TB, we assessed the drug types and dosages prescribed in the treatment of TB cases in a representative sample of health care facilities in Yunnan.We applied multistage cluster sampling using probability proportion to size to select 28 counties in Yunnan. Consecutive pulmonary TB patients were enrolled from either the TB centers of Yunnan Center of Disease Control or designated TB hospitals. Outcomes of interest included the regimen used in the treatment of new and retreatment TB patients; and the proportion of patients treated with adequate dosing of anti-TB drugs. Furthermore, we assess whether there has been reduction in the use of fluoroquinolone and second line injectables in Tuberculosis Clinical Centre (TCC after the training activity in late 2012.Of 2390 TB patients enrolled, 582 (24.4% were prescribed second line anti-TB drugs (18.0% in new cases and 60.9% in retreatment cases; 363(15.2% prescribed a fluoroquinolone. General hospitals (adjusted odds ratio (adjOR 1.97, 95% confidence interval (CI 1.47-2.66, retreatment TB cases (adjOR 4.75, 95% CI 3.59-6.27, smear positive cases (adjOR 1.69, 95% CI 1.22-2.33, and extrapulmonary TB (adjOR 2.59, 95% CI 1.66-4.03 were significantly associated with the use of fluoroquinolones. The proportion of patients treated with fluoroquinolones decreased from 41.4% before 2013 to 13.5% after 2013 (adjOR 0.19, 95% CI 0.12-0.28 in TCC. The proportion of patients with correct, under and over dosages of isoniazid was 88.2%, 1.5%, and 10.4%, respectively; of rifampicin was 50.2%, 46.8%, and 2.9%; of pyrazinamide was 67.6%, 31.7% and 0.7%; and of ethambutol was 41.4%, 57.5%, and 1.0%.The prescribing practice of anti-TB drugs was not standardized, findings with significant programmatic implication.
Full Text Available To assess and compare the prevalence, severity and prognosis of anti-TB drug induced hepatotoxicity (DIH in HIV positive and HIV negative tuberculosis (TB patients in Ethiopia.In this study, 103 HIV positive and 94 HIV negative TB patients were enrolled. All patients were evaluated for different risk factors and monitored biochemically and clinically for development of DIH. Sub-clinical hepatotoxicity was observed in 17.3% of the patients and 8 out of the 197 (4.1% developed clinical hepatotoxicity. Seven of the 8 were HIV positive and 2 were positive for HBsAg.Sub-clinical hepatotoxicity was significantly associated with HIV co-infection (p = 0.002, concomitant drug intake (p = 0.008, and decrease in CD4 count (p = 0.001. Stepwise restarting of anti TB treatment was also successful in almost all the patients who developed clinical DIH. We therefore conclude that anti-TB DIH is a major problem in HIV-associated TB with a decline in immune status and that there is a need for a regular biochemical and clinical follow up for those patients who are at risk.
Full Text Available ABSTRACT In Mexican Traditional Medicine 187 plant species are used in the treatment of respiratory conditions that may be associated with tuberculosis. In this contribution, we review the ethnobotany, chemistry and pharmacology of 63 species whose extracts have been assayed for antimycobacterial activity in vitro. Among these, the most potent is Aristolochia brevipes (MIC= 12.5 µg/mL, followed by Aristolochia taliscana, Citrus sinensis, Chrysactinia mexicana, Persea americana, and Olea europaea (MIC 95%, 50 µg/mL include: Amphipterygium adstringens, Larrea divaricata, and Phoradendron robinsoni. Several active compounds have been identified, the most potent are: Licarin A (isolated from A. taliscana, and 9-amino-9-methoxy-3,4-dihydro-2H-benzo[h]-chromen-2-one (transformation product of 9-methoxytariacuripyrone isolated from Aristolochia brevipes, both with MIC= 3.125 µg/mL, that is 8-fold less potent than the reference drug Rifampicin (MIC= 0.5 µg/mL. Any of the compounds or extracts here reviewed has been studied in clinical trials or with animal models; however, these should be accomplished since several are active against strains resistant to common drugs.
Leung, Seng Yuen; Kwok, Yue Kuen
Using the reduced form framework with inter-dependent default correlation, we perform valuation of credit default swap with counterparty risk. The inter-dependent default risk structure between the protection buyer, protection seller and the reference entity in a credit default swap are characterized by their correlated default intensities, where the default intensity of one party increases when the default of another party occurs. We explore how settlement risk and replacement cost affect th...
Moraski, Garrett C; Seeger, Natalie; Miller, Patricia A; Oliver, Allen G; Boshoff, Helena I; Cho, Sanghyun; Mulugeta, Surafel; Anderson, Jeffery R; Franzblau, Scott G; Miller, Marvin J
Increasing interest in the potent anti-tuberculosis activity and the novel target (QcrB) of imidazo[1,2-a]pyridine-3-carboxamides encouraged extended structure-activity relationship studies of additional scaffolds. This study reports on the in vitro profiling of the imidazo[2,1-b]thiazole-5-carboxamides as a new promising class of anti-tuberculosis compounds endowed with nanomolar potency against replicating and drug-resistant Mycobacterium tuberculosis (Mtb) as well as low toxicity to VERO cells. Compounds 6, 16, and 17 had MIC values 100 μM. On-target selectivity of this series was confirmed by cross-resistance of specific QcrB mutants as well as the hypersusceptibility of a mutant with a functional gene deletion of the alternative cytochrome bd oxidase. Additionally, to demonstrate selectivity, three analogues (6, 15, 17) were broadly screened against a diverse set of eight strains of bacteria, including both Gram-positive and Gram-negative as well as six disease-causing non-tuberculosis mycobacteria. Finally, compounds 16 and 17 were found to be active in macrophages infected with Mtb.
... 45 Public Welfare 3 2010-10-01 2010-10-01 false Default order. 672.10 Section 672.10 Public... HEARING PROCEDURES § 672.10 Default order. (a) Default. The Presiding Officer may find a party in default.... No finding of default on the basis of a failure to appear at a hearing shall be made against the...
... 40 Protection of Environment 1 2010-07-01 2010-07-01 false Default. 22.17 Section 22.17 Protection... Procedures § 22.17 Default. (a) Default. A party may be found to be in default: after motion, upon failure to... hearing. Default by respondent constitutes, for purposes of the pending proceeding only, an admission of...
... 40 Protection of Environment 27 2010-07-01 2010-07-01 false Default order. 305.24 Section 305.24... Default order. (a) Default. A party may be found to be in default: after motion, upon failure of the... default on the basis of failure to appear at a hearing shall be made against the Claims Official unless...
Borghans, L.; Golsteyn, B.H.H.
This paper analyzes whether defaults affect the choice for courses followed at work. In addition, we analyze whether the size of the default effect varies with employees’ personality and skill-deficiencies. We perform an experiment in which workers are hypothetically offered three courses which they
Kokholm, Thomas; Nicolato, Elisa
In reduced form default models, the instantaneous default intensity is classically the modeling object. Survival probabilities are then given by the Laplace transform of the cumulative hazard defined as the integrated intensity process. Instead, recent literature has shown a tendency towards...
Kokholm, Thomas; Nicolato, Elisa
In reduced form default models, the instantaneous default intensity is the classical modeling object. Survival probabilities are then given by the Laplace transform of the cumulative hazard defined as the integrated intensity process. Instead, recent literature tends to specify the cumulative...
Borghans, L.; Golsteyn, B.H.H.
This paper analyzes whether defaults affect the choice for courses followed at work. In addition, we analyze whether the size of the default effect varies with employees' personality and skill- deficiencies. We perform an experiment in which workers are hypothetically offered three courses which
Looney, Shannon M.
Burgeoning student loan debt indicates problems not only for the country's borrowers but also for the postsecondary system. The rise in student loan defaults signifies a rise in institutional cohort default rates (CDRs)--a measure of accountability that informs the government and the general public how well an institution prepares its students for…
Manier, M. Lisa; Reyzer, Michelle L.; Goh, Anne; Dartois, Veronique; Via, Laura E.; Barry, Clifton E.; Caprioli, Richard M.
Isoniazid (INH) is an important component of front-line anti-tuberculosis therapy with good serum pharmacokinetics but unknown ability to penetrate tuberculous lesions. However, endogenous background interferences hinder our ability to directly analyze INH in tissues. Chemical derivatization has been successfully used to measure isoniazid directly from tissue samples using matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry (IMS). MALDI targets were pretreated with trans-cinnamaldehyde (CA) prior to mounting tissue slices. Isoniazid present in the tissues was efficiently derivatized and the INH-CA product measured by MS/MS. Precoating of MALDI targets allows the tissues to be directly thaw-mounted and derivatized, thus simplifying the preparation. A time-course series of tissues from tuberculosis infected/INH dosed animals were assayed and the MALDI MS/MS response correlates well with the amount of INH determined to be in the tissues by high-performance liquid chromatography (HPLC)-MS/MS.
Raichle, Marcus E
The brain's default mode network consists of discrete, bilateral and symmetrical cortical areas, in the medial and lateral parietal, medial prefrontal, and medial and lateral temporal cortices of the human, nonhuman primate, cat, and rodent brains. Its discovery was an unexpected consequence of brain-imaging studies first performed with positron emission tomography in which various novel, attention-demanding, and non-self-referential tasks were compared with quiet repose either with eyes closed or with simple visual fixation. The default mode network consistently decreases its activity when compared with activity during these relaxed nontask states. The discovery of the default mode network reignited a longstanding interest in the significance of the brain's ongoing or intrinsic activity. Presently, studies of the brain's intrinsic activity, popularly referred to as resting-state studies, have come to play a major role in studies of the human brain in health and disease. The brain's default mode network plays a central role in this work.
... 48 Federal Acquisition Regulations System 3 2010-10-01 2010-10-01 false Default. 252.217-7009... Clauses 252.217-7009 Default. As prescribed in 217.7104(a), use the following clause: Default (DEC 1991... of default to the Contractor, terminate the whole or any part of a job order if the Contractor fails...
... 19 Customs Duties 3 2010-04-01 2010-04-01 false Default. 210.16 Section 210.16 Customs Duties... ADJUDICATION AND ENFORCEMENT Motions § 210.16 Default. (a) Definition of default. (1) A party shall be found in default if it fails to respond to the complaint and notice of investigation in the manner prescribed in...
... 24 Housing and Urban Development 2 2010-04-01 2010-04-01 false Cross default. 241.1235 Section 241... Rights and Obligations § 241.1235 Cross default. In the event the borrower commits a default under a prior recorded insured mortgage and the holder thereof initiates a foreclosure proceeding, said default...
... 40 Protection of Environment 24 2010-07-01 2010-07-01 false Default order. 209.24 Section 209.24... Orders Issued Under Section 11(d) of the Noise Control Act § 209.24 Default order. (a) Default. Respondent may be found to be in default upon failure to comply with a prehearing or hearing ruling of the...
... 13 Business Credit and Assistance 1 2010-01-01 2010-01-01 false Default. 120.938 Section 120.938... Program (504) 504 Loans and Debentures § 120.938 Default. (a) Upon occurrence of an event of default... occurrence of an event of default which does not require automatic acceleration, SBA may forbear acceleration...
Gerardi, Kristopher; Goette, Lorenz; Meier, Stephan
Unprecedented levels of US subprime mortgage defaults precipitated a severe global financial crisis in late 2008, plunging much of the industrialized world into a deep recession. However, the fundamental reasons for why US mortgages defaulted at such spectacular rates remain largely unknown. This paper presents empirical evidence showing that the ability to perform basic mathematical calculations is negatively associated with the propensity to default on one’s mortgage. We measure several aspects of financial literacy and cognitive ability in a survey of subprime mortgage borrowers who took out loans in 2006 and 2007, and match them to objective, detailed administrative data on mortgage characteristics and payment histories. The relationship between numerical ability and mortgage default is robust to controlling for a broad set of sociodemographic variables, and is not driven by other aspects of cognitive ability. We find no support for the hypothesis that numerical ability impacts mortgage outcomes through the choice of the mortgage contract. Rather, our results suggest that individuals with limited numerical ability default on their mortgage due to behavior unrelated to the initial choice of their mortgage. PMID:23798401
Gerardi, Kristopher; Goette, Lorenz; Meier, Stephan
Unprecedented levels of US subprime mortgage defaults precipitated a severe global financial crisis in late 2008, plunging much of the industrialized world into a deep recession. However, the fundamental reasons for why US mortgages defaulted at such spectacular rates remain largely unknown. This paper presents empirical evidence showing that the ability to perform basic mathematical calculations is negatively associated with the propensity to default on one's mortgage. We measure several aspects of financial literacy and cognitive ability in a survey of subprime mortgage borrowers who took out loans in 2006 and 2007, and match them to objective, detailed administrative data on mortgage characteristics and payment histories. The relationship between numerical ability and mortgage default is robust to controlling for a broad set of sociodemographic variables, and is not driven by other aspects of cognitive ability. We find no support for the hypothesis that numerical ability impacts mortgage outcomes through the choice of the mortgage contract. Rather, our results suggest that individuals with limited numerical ability default on their mortgage due to behavior unrelated to the initial choice of their mortgage.
Brown, Zachary; Johnstone, Nick; Haščič, Ivan; Vong, Laura; Barascud, Francis
We describe a randomized controlled experiment in which the default settings on office thermostats in an OECD office building were manipulated during the winter heating season, and employees' chosen thermostat setting observed over a 6-week period. Using difference-in-differences, panel, and censored regression models (to control for maximum allowable thermostat settings), we find that a 1 °C decrease in the default caused a reduction in the chosen setting by 0.38 °C, on average. Sixty-five percent of this effect could be attributed to office occupant behavior (p-value = 0.044). The difference-in-differences models show that small decreases in the default (1°) led to a greater reduction in chosen settings than large decreases (2°). We also find that office occupants who were more apt to adjust their thermostats prior to the intervention were less susceptible to the default. We conclude that this kind of intervention can increase building-level energy efficiency, and discuss potential explanations and broader policy implications of our findings. - Highlights: • We conduct a randomized controlled trial to test if thermostat defaults affect agent behavior. • Two treatments (schedules of default settings) were tested against a control for 6 weeks at OECD. • Small changes in defaults had a greater effect on chosen settings than larger changes in defaults. • Occupants who frequently changed their thermostats in baseline were less affected by defaults. • Thermostat defaults in office environments can be manipulated to increase energy efficiency
Nov 1, 1997 ... tuberculosis treatment at Freegold Mines. Objectives. 1. To establish the rates of attendance and collection of anti-tuberculosis drugs. 2. To detennine prevalence of non-compliance by means of urine tests. Design. A cross-sectional study conducted over 2 weeks at mine medical stations. Method.
Mehra, Darshan; Kaushik, Rajeev M; Kaushik, Reshma; Rawat, Jagdish; Kakkar, Rajesh
Initial default is a serious issue which can enhance the transmission of TB. We determined the magnitude of and the causative factors for initial default among sputum-positive pulmonary TB (PTB) patients. In this prospective study, 2310 patients attending a referral hospital in Uttarakhand state, north India, with presumptive TB were investigated and 555 patients with sputum-positive PTB were followed-up for initiation of anti-TB treatment (ATT) during 2010-2012. The patients not confirmed as having started ATT were considered initial defaulters. Initial default was seen in 120 (21.6%) patients comprising 22 (18.3%) defaulters during diagnosis and 98 (81.6%) defaulters after referral for directly observed treatment, short-course (DOTS). The initial default rate was significantly higher among patients from rural areas than urban areas, illiterate patients than literate patients and smokeless tobacco-users than non-users (pdefault among patients referred for DOTS were limited trust in DOTS (n = 44, 44.8%), adverse effects of previous ATT (n = 41, 41.8%), dissatisfaction with health services (n = 38, 38.7%), local deaths while taking DOTS (n = 28, 28.5%), advice by others against DOTS (n = 25, 25.5%), disbelief in the diagnosis (n = 18, 18.3%) and patient death before starting treatment (n = 4, 4.0%). A high initial default rate was seen among patients with PTB. There is an urgent need to promote public awareness to lower the initial default rate.
Jessen, Cathrine; Lando, David
. A notable exception is a model with stochastic volatility of assets. In this case both the ranking of firms and the estimated default probabilities using distance-to-default perform significantly worse. We therefore propose a volatility adjustment of the distance-to-default measure, that significantly...... simulations to investigate the robustness of the distance-to-default measure to different model specifications. Overall we find distance-to-default to be robust to a number of deviations from the simple Merton model that involve different asset value dynamics and different default triggering mechanisms...
Full Text Available I introduce the notion of ``neglect defaulting,'' which labels the propensity to neglect possibilities which are ordinarily sensibly neglected. In familiar contexts we are well-tuned to recognize when to override the default. But outside the range of familiar experience --- here in the artificial context of puzzles --- these ordinarily benign defaults can make it difficult for even sophisticated subjects, such as readers of this note, to avoid responses which on reflection will be seen as obviously mistaken. A detail of particular importance is that, although subjects are easily prompted to take one step in the direction of reaching a sound response, the tendency to then neglect to consider that another step may be needed is remarkably strong. In each of the five examples the needed but usually neglected second step is quite trivial. Concluding remarks point to consequences for larger questions outside the range of familiar experience, in politics and other contexts out of scale with everyday experience.
Bille, Philip; Gørtz, Inge Li; Skjoldjensen, Frederik Rye
of states and transitions) of the subsequence automaton is O(nσ) and that this bound is asymptotically optimal. In this paper, we consider subsequence automata with default transitions, that is, special transitions to be taken only if none of the regular transitions match the current character, and which do...... not consume the current character. We show that with default transitions, much smaller subsequence automata are possible, and provide a full trade-off between the size of the automaton and the delay, i.e., the maximum number of consecutive default transitions followed before consuming a character......(1), thus matching the bound for the standard subsequence automaton construction. Finally, we generalize the result to multiple strings. The key component of our result is a novel hierarchical automata construction of independent interest....
Bille, Philip; Gørtz, Inge Li; Skjoldjensen, Frederik Rye
of states and transitions) of the subsequence automaton is O(nσ) and that this bound is asymptotically optimal. In this paper, we consider subsequence automata with default transitions, that is, special transitions to be taken only if none of the regular transitions match the current character, and which do...... not consume the current character. We show that with default transitions, much smaller subsequence automata are possible, and provide a full trade-off between the size of the automaton and the delay, i.e., the maximum number of consecutive default transitions followed before consuming a character......(nσ) and delay O(1), thus matching the bound for the standard subsequence automaton construction. The key component of our result is a novel hierarchical automata construction of independent interest....
Miriam Bobadilla-del Valle
Full Text Available Mycobacterium tuberculosis causes the majority of tuberculosis (TB cases in humans; however, in developing countries, human TB caused by M. bovis may be frequent but undetected. Human TB caused by M. bovis is considered a zoonosis; transmission is mainly through consumption of unpasteurized dairy products, and it is less frequently attributed to animal-to-human or human-to-human contact. We describe the trends of M. bovis isolation from human samples and first-line drug susceptibility during a 15-year period in a referral laboratory located in a tertiary care hospital in Mexico City.Data on mycobacterial isolates from human clinical samples were retrieved from the laboratory's database for the 2000-2014 period. Susceptibility to first-line drugs: rifampin, isoniazid, streptomycin (STR and ethambutol was determined. We identified 1,165 isolates, 73.7% were M. tuberculosis and 26.2%, M. bovis. Among pulmonary samples, 16.6% were M. bovis. The proportion of M. bovis isolates significantly increased from 7.8% in 2000 to 28.4% in 2014 (X(2trend, p<0.001. Primary STR resistance was higher among M. bovis compared with M. tuberculosis isolates (10.9% vs.3.4%, p<0.001. Secondary multidrug resistance (MDR rates were 38.5% and 34.4% for M. bovis and M. tuberculosis, respectively (p = 0.637. A rising trend of primary STR monoresistance was observed for both species (3.4% in 2000-2004 vs. 7.6% in 2010-2014; p = 0.02.There is a high prevalence and a rising trend of M. bovis isolates in our region. The proportion of pulmonary M. bovis isolates is higher than in previous reports. Additionally, we report high rates of primary anti-tuberculosis resistance and secondary MDR in both M. tuberculosis and M. bovis. This is one of the largest reports on drug susceptibility of M. bovis from human samples and shows a significant proportion of first-line anti-tuberculosis drug resistance.
Zlatev, Julian J; Daniels, David P; Kim, Hajin; Neale, Margaret A
Current theories suggest that people understand how to exploit common biases to influence others. However, these predictions have received little empirical attention. We consider a widely studied bias with special policy relevance: the default effect, which is the tendency to choose whichever option is the status quo. We asked participants (including managers, law/business/medical students, and US adults) to nudge others toward selecting a target option by choosing whether to present that target option as the default. In contrast to theoretical predictions, we find that people often fail to understand and/or use defaults to influence others, i.e., they show "default neglect." First, in one-shot default-setting games, we find that only 50.8% of participants set the target option as the default across 11 samples ( n = 2,844), consistent with people not systematically using defaults at all. Second, when participants have multiple opportunities for experience and feedback, they still do not systematically use defaults. Third, we investigate beliefs related to the default effect. People seem to anticipate some mechanisms that drive default effects, yet most people do not believe in the default effect on average, even in cases where they do use defaults. We discuss implications of default neglect for decision making, social influence, and evidence-based policy.
Kehinde, Aderemi; Adefisan, Adedoyin; Adebayo, Olayinka; Adaramoye, Oluwatosin
Tuberculosis (TB) is a global health problem. The effects of anti-TB drugs on male reproductive system have not been properly evaluated. We investigated the effects of anti-TB drugs on testicular antioxidant indices, sperm characteristics and hormonal levels in rats, and the protective role of kolaviron (KV), a biflavonoid from Garcinia kola seed. Twenty-eight male Wistar rats were assigned into four groups and orally treated with corn oil (control), anti-TB drugs [4-Tabs=isoniazid (5 mg/kg), rifampicin (10 mg/kg), pyrazinamide (15 mg/kg) and ethambutol (15 mg/kg) in combination], anti-TB drugs +KV and KV alone (200 mg/kg). Anti-TB drugs and KV were given three times per week for 8 weeks. In vitro, reducing power, inhibition of lipid peroxidation (LPO), diphenyl-1-picrylhydrazyl (DPPH) and hydroxyl radical scavenging effects of KV were examined. KV at 10, 20, 50 and 100 μg/mL showed strong reducing potential and effectively scavenged DPPH and OH radicals in a concentration-dependent manner. Furthermore, KV significantly inhibited LPO in rats' liver homogenate. In vivo, administration of 4-Tabs caused a significant (phormone and testosterone. Co-administration of KV with 4-Tabs normalized body weight, enhanced antioxidant system and improved sperm characteristics. Kolaviron protects male reproductive system from oxidative damage by anti-tuberculosis drugs via the antioxidative mechanism.
Full Text Available An epidemiological study was carried out in 2004-2005 at the anti-tuberculosis centre of Divo (Ivory Coast to collect sera from patients who consulted for tuberculosis suspicion and to estimate the seroprevalence of human paragonimosis in the context of a systematic screening. No Paragonimus egg was found in the stools and/or sputa of the 167 persons investigated. In contrast, 41 sera were ascertained with antibodies against Paragonimus africanus using ELISA testing. As the optical density (OD values related to seropositive findings were found under 0.6 (the minimal OD to detect an active paragonimosis, the above antibody titres might originate from patients in chronic or in convalescent stages, or might result of cross reactions with trematodes. Concomitantly, dissection of local crabs (Callinectes marginatus demonstrated the presence of Paragonimus metacercariae in six out of 34 examined. The parasite burdens in crabs ranged from two to 35 cysts with a mean diameter of 302 μm. In Ivory Coast, the locality of Divo must be considered an at-risk zone in reason of the presence of anti-Paragonimus antibodies in several human sera and the presence of infected crabs at the local market.
Rosa A. S. Couto
Full Text Available Herein we describe the development, characterization and application of an electrochemical sensor based on the use of Nafion/MWCNT-modified screen-printed carbon electrodes (SPCEs for the voltammetric detection of the anti-tuberculosis (anti-TB drug ethambutol (ETB. The electrochemical behaviour of the drug at the surface of the developed Nafion/MWCNT-SPCEs was studied through cyclic voltammetry (CV and square wave voltammetry (SWV techniques. Electrochemical impedance spectroscopy (EIS and scanning electron microscopy (SEM were employed to characterize the modified surface of the electrodes. Results showed that, compared to both unmodified and MWCNTs-modified SPCEs, negatively charged Nafion/MWCNT-SPCEs remarkably enhanced the electrochemical sensitivity and selectivity for ETB due to the synergistic effect of the electrostatic interaction between cationic ETB molecules and negatively charged Nafion polymer and the inherent electrocatalytic properties of both MWCNTs and Nafion. Nafion/MWCNT-SPCEs provided excellent biocompatibility, good electrical conductivity, low electrochemical interferences and a high signal-to-noise ratio, providing excellent performance towards ETB quantification in microvolumes of human urine and human blood serum samples. The outcomes of this paper confirm that the Nafion/MWCNT-SPCE-based device could be a potential candidate for the development of a low-cost, yet reliable and efficient electrochemical portable sensor for the low-level detection of this antimycobacterial drug in biological samples.
Full Text Available Capuramycin and a few semisynthetic derivatives have shown potential as anti-tuberculosis antibiotics.To understand their mechanism of action and structureactivity relationships a 3D-QSAR and molecular docking studies were performed. A set of 52 capuramycin derivatives for the training set and 13 for the validation set was used. A highly predictive MFA model was obtained with crossvalidated q2 of 0.398, and non-cross validated partial least-squares (PLS analysis showed a conventional r2 of 0.976 and r2pred of 0.839. The model has an excellent predictive ability. Combining the 3D-QSAR and molecular docking studies, a number of new capuramycin analogs with predicted improved activities were designed. Biological activity tests of one analog showed useful antibiotic activity against Mycobacterium smegmatis MC2 155 and Mycobacterium tuberculosis H37Rv. Computer-aided molecular docking and 3D-QSAR can improve the design of new capuramycin antimycobacterial antibiotics.
... disbursement targets, especially in rural areas, also contributes to loan default. Lack of awareness regarding various fees and charges for loan processing purposes deducted at the outset was also found to be a problem. Bank data shows that despite a large amount of excess liquidity, interest rates charged on loans have ...
Sunstein, Cass R.; Reisch, Lucia A.
. The underlying reasons include the power of suggestion; inertia and procrastination; and loss aversion. If well-chosen, climate-friendly defaults are likely to have large effects in reducing the economic and environmental harms associated with various products and activities. In deciding whether to establish...
... 17 Commodity and Securities Exchanges 2 2010-04-01 2010-04-01 false Default; motion to set aside default. 201.155 Section 201.155 Commodity and Securities Exchanges SECURITIES AND EXCHANGE COMMISSION RULES OF PRACTICE Rules of Practice General Rules § 201.155 Default; motion to set aside default. (a) A...
... 49 Transportation 8 2010-10-01 2010-10-01 false Default for failure to comply with schedule; effect of default. 1112.3 Section 1112.3 Transportation Other Regulations Relating to Transportation... § 1112.3 Default for failure to comply with schedule; effect of default. If a party fails to comply with...
Jessen, Cathrine; Lando, David
Distance-to-default is a remarkably robust measure for ranking firms according to their risk of default. The ranking seems to work despite the fact that the Merton model from which the measure is derived produces default probabilities that are far too small when applied to real data. We use simul...
... 39 Postal Service 1 2010-07-01 2010-07-01 false Default. 965.7 Section 965.7 Postal Service UNITED STATES POSTAL SERVICE PROCEDURES RULES OF PRACTICE IN PROCEEDINGS RELATIVE TO MAIL DISPUTES § 965.7 Default. A party who fails to file the submittal required by § 965.5 may be held in default and the...
... 15 Commerce and Foreign Trade 1 2010-01-01 2010-01-01 false Default. 280.208 Section 280.208... Enforcement § 280.208 Default. (a) General. Failure of the respondent to file an answer within the time...) Petition to set aside default—(1) Procedure. Upon petition filed by a respondent against whom a default...
... 31 Money and Finance: Treasury 1 2010-07-01 2010-07-01 false Answer; default. 10.64 Section 10.64... SERVICE Rules Applicable to Disciplinary Proceedings § 10.64 Answer; default. (a) Filing. The respondent's... need be adduced at a hearing. (d) Default. Failure to file an answer within the time prescribed (or...
... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Default. 128.4 Section 128.4 Foreign Relations DEPARTMENT OF STATE INTERNATIONAL TRAFFIC IN ARMS REGULATIONS ADMINISTRATIVE PROCEDURES § 128.4 Default. (a... default. The case shall then be referred to the Administrative Law Judge for consideration in a manner as...
As reported, most DC pension scheme participants simply follow proposed defaults, even though they have the freedom to choose. Consequently, default designs have dramatic impacts on individuals’retirement saving outcomes. Given the fact that the default design matters, this paper evaluates
... 39 Postal Service 1 2010-07-01 2010-07-01 false Default. 952.11 Section 952.11 Postal Service... AND LOTTERY ORDERS § 952.11 Default. (a) If the Respondent fails to file an answer within the time specified in the notice of answer and hearing, he shall be deemed in default, and to have waived hearing and...
... 10 Energy 4 2010-01-01 2010-01-01 false Default order. 820.33 Section 820.33 Energy DEPARTMENT OF ENERGY PROCEDURAL RULES FOR DOE NUCLEAR ACTIVITIES Enforcement Process § 820.33 Default order. (a) Default. The Presiding Officer, upon motion by a party or the filing of a Notice of Intent to issue a...
... 24 Housing and Urban Development 2 2010-04-01 2010-04-01 false Default. 320.31 Section 320.31 Housing and Urban Development Regulations Relating to Housing and Urban Development (Continued) GOVERNMENT... SECURITIES Bond-Type Securities § 320.31 Default. Upon default of the issuer, the Association has the right...
... 24 Housing and Urban Development 4 2010-04-01 2010-04-01 false Financial default. 886.314 Section... Program for the Disposition of HUD-Owned Projects § 886.314 Financial default. In the event of a financial default under the project mortgage, HUD shall have the right to make subsequent housing assistance...
Kiefer, Nicholas Maximilian; Larson, C. Erik
in a discrete state space. In a simple case, the states could be default/non-default; in other models relevant for credit modeling the states could be credit scores or payment status (30 dpd, 60 dpd, etc.). Here we focus on the use of stochastic counting processes for mortgage default modeling, using data...
... 10 Energy 2 2010-01-01 2010-01-01 false Default. 110.110 Section 110.110 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) EXPORT AND IMPORT OF NUCLEAR EQUIPMENT AND MATERIAL Hearings § 110.110 Default. When a participant fails to act within a specified time, the presiding officer may consider him in default, issue an...
... 24 Housing and Urban Development 2 2010-04-01 2010-04-01 false Default provision. 201.16 Section... PROPERTY IMPROVEMENT AND MANUFACTURED HOME LOANS Loan and Note Provisions § 201.16 Default provision. The... default by the borrower. ...
... 39 Postal Service 1 2010-07-01 2010-07-01 false Default; Appearances. 953.7 Section 953.7 Postal... § 953.7 Default; Appearances. If a timely reply to the appeal is not filed, the presiding officer shall... Inspector or his or her designee is in default. Whenever the General Counsel or the Chief Postal Inspector...
... 15 Commerce and Foreign Trade 2 2010-01-01 2010-01-01 false Default. 766.7 Section 766.7 Commerce... PROCEEDINGS § 766.7 Default. (a) General. Failure of the respondent to file an answer within the time provided... aside default—(1) Procedure. Upon petition filed by a respondent against whom a default order has been...
... 24 Housing and Urban Development 4 2010-04-01 2010-04-01 false Substantial default. 902.79 Section... PUBLIC HOUSING ASSESSMENT SYSTEM PHAS Incentives and Remedies § 902.79 Substantial default. (a) Events or conditions that constitute substantial default. The following events or conditions shall constitute...
... 29 Labor 9 2010-07-01 2010-07-01 false Loan default. 4043.67 Section 4043.67 Labor Regulations... CERTAIN OTHER NOTIFICATION REQUIREMENTS Advance Notice of Reportable Events § 4043.67 Loan default. (a) Reportable event and information required. Advance notice is required for a loan default, as described in...
... 27 Alcohol, Tobacco Products and Firearms 2 2010-04-01 2010-04-01 false Default. 41.116 Section 41... Deferred Payment of Tax in Puerto Rico on Tobacco Products § 41.116 Default. Where a check or money order... the full amount of tax due thereunder, or where a bonded manufacturer is otherwise in default in...
Roos, N.; Roos, Nico
Reiter's Default Logic is one of the most popular formalisms for describing default reasoning. One important defect of Default Logic is, however, the inability to reason by cases. Over the years, several solutions for this problem have been proposed. All these proposals deal with deriving new
... 10 Energy 4 2010-01-01 2010-01-01 false Default. 800.304 Section 800.304 Energy DEPARTMENT OF... ASSISTANCE Loan Administration § 800.304 Default. (a) In the event that the borrower fails to perform the terms and conditions of the loan, the borrower shall be in default and the Secretary shall have the...
... 39 Postal Service 1 2010-07-01 2010-07-01 false Default. 963.11 Section 963.11 Postal Service... PANDERING ADVERTISEMENTS STATUTE, 39 U.S.C. 3008 § 963.11 Default. If a petitioner, without notice or cause... thereupon may find the petitioner to be in default and refer the matter to the Judicial Officer for...
... 39 Postal Service 1 2010-07-01 2010-07-01 false Default. 959.10 Section 959.10 Postal Service... STATUTES § 959.10 Default. (a) If the respondent fails to file an answer within the time specified in the notice of hearing, the respondent shall be deemed in default and to have waived hearing and further...
... 24 Housing and Urban Development 1 2010-04-01 2010-04-01 false Default. 26.41 Section 26.41... PROCEDURES Hearings Pursuant to the Administrative Procedure Act Prehearing Procedures § 26.41 Default. (a) General. The respondent may be found in default, upon motion, for failure to file a timely response to the...
... 29 Labor 9 2010-07-01 2010-07-01 false Loan default. 4043.34 Section 4043.34 Labor Regulations... CERTAIN OTHER NOTIFICATION REQUIREMENTS Post-Event Notice of Reportable Events § 4043.34 Loan default. (a) Reportable event. A reportable event occurs for a plan whenever there is a default by a member of the plan's...
... 7 Agriculture 14 2010-01-01 2009-01-01 true Liquidation; default. 1951.891 Section 1951.891... Liquidation; default. (a) In the event that FmHA or its successor agency under Public Law 103-354 takes over... Public Law 103-354 in connection with any default or breach of conditions under any loan made hereunder...
Jessen, Cathrine; Lando, David
Distance-to-default (DD) is a measure of default risk derived from observed stock prices and book leverage using the structural credit risk model of Merton (1974). Despite the simplifying assumptions that underlie its derivation, DD has proven empirically to be a strong predictor of default. We use...
Park, Ki-Ho; Lee, Mi Suk; Lee, Sang-Oh; Choi, Sang-Ho; Kim, Yang Soo; Woo, Jun Hee; Kim, Sung-Han
Limited data are available regarding the incidence and outcomes of lymphadenopathy after completing tuberculosis (TB) treatment. We prospectively evaluated the incidence and outcomes of post-treatment lymphadenopathy in 154 patients with newly diagnosed lymph node TB (group 1) and in 12 patients previously treated for TB (group 2). We assessed the rates of microbiological recurrence, clinical recurrence, and post-treatment paradoxical response (PR) (defined as no microbiological recurrence with spontaneous improvement). Post-treatment lymphadenopathy occurred in 24 (15.6%) patients of group 1 and in 12 patients of group 2. Re-biopsy was performed in 23 of these 36 patients. AFB stain was positive in four (17.4%) cases, and TB-PCR was positive in 11 (47.8%), but all samples were sterile (no microbiological recurrence). Granuloma was present in 12 (52.2%) histological specimens. Thirty-three (91.7%) of the 36 patients with lymphadenopathy improved spontaneously (post-treatment PR) and 3 (8.3%) were improved with retreatment (clinical recurrence). The overall incidence of post-treatment PR in patients with lymph node TB (group 1) was 8.6 per 100 person-years (95% CI, 5.8-12.7). Lymphadenopathy after TB treatment was more likely to be associated with post-treatment PR rather than with microbiological recurrence, and it should be monitored until PR resolve. Copyright © 2013 The British Infection Association. Published by Elsevier Ltd. All rights reserved.
YONG KYUN KIM
Full Text Available Do differences in the inequality of income affect the likelihood that democratic governments decide not to honor their foreign debt contracts? I argue that sovereign default involves an intertemporal tradeoff between an immediate consumption boost and a future tax increase. Since a poorer voter internalizes less of the future cost of default, as the median is poorer, the majority’s demand for default increases. Therefore, greater income inequality implies a higher default risk. I then present a signaling game that models strategic selection that a sovereign must go through to get to the default decision node. I show that sovereign default is most likely to actually occur when the level of income inequality is intermediate. The intuition is that sovereign default occurs when risky sovereigns successfully induce creditors to provide a loan, but the most risky ones are among those least able to do so. Empirical findings support the claim.
Results. The study showed that the majority (38.7%) of patients with diabetes on the public sector register were from the district of eThekwini. Positive correlations were found between the prevalence of diabetes, the mortality rate and the number of defaulters (patients with diabetes who did not return for regular treatment).
outcomes.1,2 Rates of treatment default as high as 30% to 40% have been reported in the ... Objective: To assess the pattern of and factors associated with outpatient clinic attendance among patients diagnosed with schizophrenia at a Nigerian ..... health system- the impact of patients who leave care. Psychiatric Services ...
A descriptive cross sectional study was carried out at Chitungwiza Central. Hospital, a tertiary facility offering in and outpatient rehabilitation services in Zimbabwe. Caregivers of children who had congenital disabilities. (N=40) and who had a history of defaulting treatment but were available during the data collection period ...
Gatterbauer, Wolfgang; Meliou, Alexandra; Suciu, Dan
We show that the default-all propagation scheme for database annotations is dangerous. Dangerous here means that it can propagate annotations to the query output which are semantically irrelevant to the query the user asked. This is the result of considering all relationally equivalent queries and returning the union of their where-provenance in an attempt to define a propagation scheme that is insensitive to query rewriting. We propose an alternative query-rewrite-insensitive (QRI) where-pro...
Full Text Available Abstract Background More than 1 million tuberculosis (TB patients are receiving the standard anti-TB treatment provided by China National Tuberculosis Prevention and Control Scheme (CNTS in China every year. Adverse reactions (ADRs induced by anti-TB drugs could both do harm to patients and lead to anti-TB treatment failure. The ADACS aimed to explore ADRs' incidences, prognoses, economical and public health impacts for TB patients and TB control, and build a DNA bank of TB patients. Methods/Design Multiple study designs were adopted. Firstly, a prospective cohort with 4488 sputum smears positive pulmonary tuberculosis patients was established. Patients were followed up for 6-9 months in 52 counties of four regions. Those suspected ADRs should be checked and confirmed by Chinese State Food and Drug Administration (SFDA. Secondly, if the suspected ADR was anti-TB drug induced liver injury (ATLI, a nested case-control study would be performed which comprised choosing a matched control and doing a plus questionnaire inquiry. Thirdly, health economical data of ADRs would be collected to analyze financial burdens brought by ADRs and cost-effectiveness of ADRs' treatments. Fourthly, a drop of intravenous blood for each patient was taken and saved in FTA card for DNA banking and genotyping. Finally, the demographic, clinical, environmental, administrative and genetic data would be merged for the comprehensive analysis. Discussion ADACS will give an overview of anti-TB drugs induced ADRs' incidences, risk factors, treatments, prognoses, and clinical, economical and public health impacts for TB patients applying CNTS regimen in China, and provide suggestions for individualized health care and TB control policy.
Shallo Daba Hamusse
Full Text Available Abstract Background Multidrug-resistant tuberculosis (MDR-TB drugs which is resistant to the major first-line anti-TB drugs, Isoniazid and Rifampicin, has become a major global challenge in tuberculosis (TB control programme. However, its burden at community level is not well known. Thus, the aim of study was to assess the prevalence of primary and secondary resistance to any first line anti-TB drugs and MDR TB in Hitossa District of Oromia Regional State, Central Ethiopia. Methods Population based cross- sectional study was conducted on individuals aged ≥15 years. Those with symptoms suggestive of TB were interviewed and two sputum specimens were collected from each and examined using Lowenstein-Jensen (LJ culture medium. Further, the isolates were confirmed by the Ziehl-Neelsen microscopic examination method. Drug susceptibility test (DST was also conducted on LJ medium using a simplified indirect proportion method. The resistance strains were then determined by percentage of colonies that grew on the critical concentration of Isoniazid, Streptomycin, Rifampicin and Ethambutol. Results The overall resistance of all forms of TB to any first-line anti-TB drug was 21.7 %. Of the total new and previously treated culture positive TB cases, 15.3 and 48.8 % respectively were found to be a resistant to any of the first-line anti-TB drugs. Further, of all forms of TB, the overall resistance of MDR-TB was 4.7 %. However, of the total new TB cases, 2.4 % had primary while 14.3 % had secondary MDR-TB. Resistance to any of the first-line anti-TB drugs (adjusted odd ratio (AOR, 8.1; 95 % CI: 2.26–29.30 and MDR-TB (AOR, 7.1; 95 % CI: 2.6–43.8 was found to be linked with previous history of anti-TB treatment. Conclusions The study has identified a high rate of primary and secondary resistance to any of the first-line anti-TB drugs and MDR-TB in the study area. The resistance may have resulted from sub-optimal performance of directly observed
Comparative Modulation of Levels of Oxidative Stress in the Liver of Anti-Tuberculosis Drug Treated Wistar Rats by Vitamin B12, Beta-Carotene, and Spirulina fusiformis: Role of NF-κB, iNOS, IL-6, and IL-10.
Joseph Martin, Sherry; Evan Prince, Sabina
Isoniazid (INH) and Rifampicin (RIF) are known hepatotoxic agents. We compared the efficacy of Spirulina fusiformis and its active components vitamin B12 and beta-carotene in attenuating INH and RIF induced hepatotoxicity. We also tried to elucidate the inflammatory mechanism behind anti-tuberculosis drug induced hepatotoxicity. INH and RIF were administered to Wistar albino rats for 28 days to induce hepatotoxicity. S. fusiformis, vitamin B12, and beta-carotene were co-administered with INH and RIF and their hepatoprotective, antioxidant, and immunomodulatory roles were studied through blood and liver analysis. Changes induced by INH and RIF in antioxidants, cytokines (IL-6 and IL-10) and expression of Nuclear Factor-κB (NF-κB) and Nitric Oxide Synthase (iNOS) were also studied. Supplement treatment caused restoration of liver function parameters to normal levels along with reversal of inflammatory changes in IL-6 and IL-10 levels. Liver PCNA, iNOS, and NF-κB expression were reduced in the supplement treated tissues compared to INH and RIF treated rats as evidenced by immunohistochemistry and quantitative PCR. Correlation of IL-6 levels, PCNA, and iNOS with NF-κB showed its pivotal role in the inflammatory process. Study shows the pivotal role of NF-kB and the equivalence in antioxidant efficacy of vitamin B12 and beta-carotene compared to Spirulina fusiformis. J. Cell. Biochem. 118: 3825-3833, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.
Due to the rise of drug resistant forms of tuberculosis there is an urgent need for novel antibiotics to effectively combat these cases and shorten treatment regimens. Recently, drug screens using whole cell analyses have been shown to be successful. However, current high-throughput screens focus mostly on stricto sensu life-death screening that give little qualitative information. In doing so, promising compound scaffolds or non-optimized compounds that fail to reach inhibitory concentrations are missed. To accelerate early TB drug discovery, we performed RNA sequencing on Mycobacterium tuberculosis and Mycobacterium marinum to map the stress responses that follow upon exposure to sub-inhibitory concentrations of antibiotics with known targets: ciprofloxacin, ethambutol, isoniazid, streptomycin and rifampicin. The resulting dataset comprises the first overview of transcriptional stress responses of mycobacteria to different antibiotics. We show that antibiotics can be distinguished based on their specific transcriptional stress fingerprint. Notably, this fingerprint was more distinctive in M. marinum. We decided to use this to our advantage and continue with this model organism. A selection of diverse antibiotic stress genes was used to construct stress reporters. In total, three functional reporters were constructed to respond to DNA damage, cell wall damage and ribosomal inhibition. Subsequently, these reporter strains were used to screen a small anti-TB compound library to predict the mode of action. In doing so, we could identify the putative mode of action for three novel compounds, which confirms our approach.
Zaverucha-do-Valle, Camila; Monteiro, Sérgio P; El-Jaick, Kênia B; Rosadas, Leonardo A; Costa, Marli J M; Quintana, Marcel S B; de Castro, Liane
Tuberculosis (TB) is still a major health concern and side-effects related to the treatment, especially drug-induced hepatotoxicity (DIH), should be better investigated. In the present study, a possible association between anti-TB DIH and cigarette smoking, N-acetyltransferase 2 (NAT2), Cytochrome P450 2E1 (CYP2E1) and Cytochrome P450 3A4 (CYP3A4) genotypes was studied in 131 TB Brazilian patients. The NAT2 and CYP3A4 genetic polymorphisms were determined using a polymerase chain reaction (PCR) direct sequencing approach and genetic polymorphisms of CYP2E1 gene were determined by restriction fragment length polymorphism (RFLP). The risk of anti-TB DIH was lower in rapid/intermediate acetylators when compared to slow acetylators (OR: 0.34, CI 95: 0.16-0.71; p < 0.01). A decreased risk of developing anti-TB DIH was also observed in active smokers when compared to non-smokers (OR: 0.28, 95 CI: 0.11-0.64; p < 0.01). Significant association between CYP3A4 genotypes and hepatotoxicity was not observed, as well as between CYP2E1 genotype and hepatotoxicity, whose frequency of patients with wild homozygous was more prevalent. The anti-TB drugs interactions with smoking on hepatotoxicity, as well as the NAT2 phenotype, may require to adjust therapeutic regimen dosages or alarm in case of adverse event developments. Copyright © 2014 Elsevier Ltd. All rights reserved.
Full Text Available The slow growth of Mycobacterium tuberculosis (Mtb, the causative agent of tuberculosis (TB, hinders development of new diagnostics, therapeutics and vaccines. Using non-invasive real-time imaging technologies to monitor the disease process in live animals would facilitate TB research in all areas. We developed fluorescent protein (FP expressing Mycobacterium bovis BCG strains for in vivo imaging, which can be used to track bacterial location, and to quantify bacterial load in live animals. We selected an optimal FP for in vivo imaging, by first cloning six FPs: tdTomato, mCherry, mPlum, mKate, Katushka and mKeima, into mycobacteria under either a mycobacterial Hsp60 or L5 promoter, and compared their fluorescent signals in vitro and in vivo. Fluorescence from each FP-expressing strain was measured with a multimode reader using the optimal excitation and emission wavelengths for the FP. After normalizing bacterial numbers with optical density, the strain expressing L5-tdTomato displayed the highest fluorescence. We used the tdTomato-labeled M. bovis BCG to obtain real-time images of pulmonary infections in living mice and rapidly determined the number of bacteria present. Further comparison between L5-tdTomato and Hsp60-tdTomato revealed that L5-tdTomato carried four-fold more tdTomato gene copies than Hsp60-tdTomato, which eventually led to higher protein expression of tdTomato. Evaluating anti-TB efficacy of rifampicin and isoniazid therapy in vitro and in vivo using the L5-tdTomato strain demonstrated that this strain can be used to identify anti-TB therapeutic efficacy as quickly as 24 h post-treatment. These M. bovis BCG reporter strains represent a valuable new tool for evaluation of therapeutics, vaccines and virulence.
... 49 Transportation 4 2010-10-01 2010-10-01 false Avoiding defaults. 260.49 Section 260.49 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL RAILROAD ADMINISTRATION... REHABILITATION AND IMPROVEMENT FINANCING PROGRAM Procedures To Be Followed in the Event of Default § 260.49...
We examine monetary policy options for a small open economy where sovereign default might occur due to intertemporal insolvency. Under interest rate policy and floating exchange rates the equilibrium is indetermined. Under a fixed exchange rate the equilibrium is uniquely determined and independent of sovereign default.
... Administrative Law Judge (or the Secretary's designee) pursuant to § 501.729(b). (b) In deciding whether to determine the proceedings against a party deemed to be in default, the Administrative Law Judge shall... default and the Administrative Law Judge (or the Secretary's designee during review proceedings) may...
Koopman, S.J.; Lucas, A.
Various economic theories are available to explain the existence of credit and default cycles. There remains empirical ambiguity, however, as to whether these cycles coincide. Recent papers suggest by their empirical research set-up that they do, or at least that defaults and credit spreads tend to
... 39 Postal Service 1 2010-07-01 2010-07-01 false Default. 964.6 Section 964.6 Postal Service UNITED STATES POSTAL SERVICE PROCEDURES RULES OF PRACTICE GOVERNING DISPOSITION OF MAIL WITHHELD FROM DELIVERY PURSUANT TO 39 U.S.C. 3003, 3004 § 964.6 Default. If a Petitioner fails to appear at the hearing without...
... 14 Aeronautics and Space 4 2010-01-01 2010-01-01 false Default. 302.409 Section 302.409 Aeronautics and Space OFFICE OF THE SECRETARY, DEPARTMENT OF TRANSPORTATION (AVIATION PROCEEDINGS) PROCEDURAL REGULATIONS RULES OF PRACTICE IN PROCEEDINGS Rules Applicable to Enforcement Proceedings § 302.409 Default...
... 10 Energy 1 2010-01-01 2010-01-01 false Default. 2.320 Section 2.320 Energy NUCLEAR REGULATORY COMMISSION RULES OF PRACTICE FOR DOMESTIC LICENSING PROCEEDINGS AND ISSUANCE OF ORDERS Rules of General... § 2.320 Default. If a party fails to file an answer or pleading within the time prescribed in this...
Y-H. Tan (Yao-Hua)
textabstractWe present what we call Constructive Default Logic (CDL) - a default logic in which the fixed-point definition of extensions is replaced by a constructive definition which yield so-called constructive extensions. Selection functions are used to represent explicitly the control of the
... 39 Postal Service 1 2010-07-01 2010-07-01 false Default. 954.9 Section 954.9 Postal Service UNITED STATES POSTAL SERVICE PROCEDURES RULES OF PRACTICE IN PROCEEDINGS RELATIVE TO THE DENIAL, SUSPENSION, OR REVOCATION OF PERIODICALS MAIL PRIVILEGES § 954.9 Default. If a publisher fails to appear at the hearing, the...
... 48 Federal Acquisition Regulations System 3 2010-10-01 2010-10-01 false Default. 245.7309-7 Section 245.7309-7 Federal Acquisition Regulations System DEFENSE ACQUISITION REGULATIONS SYSTEM... Default. If the successful Bidder fails to make full payment, remove property by the specified date, or...
Gu, Xin; Hoijtink, Herbert; Mulder, J,
This paper investigates the classical type I and type II error probabilities of default Bayes factors for a Bayesian t test. Default Bayes factors quantify the relative evidence between the null hypothesis and the unrestricted alternative hypothesis without needing to specify prior distributions for
... 12 Banks and Banking 6 2010-01-01 2010-01-01 false Default. 622.81 Section 622.81 Banks and Banking FARM CREDIT ADMINISTRATION FARM CREDIT SYSTEM RULES OF PRACTICE AND PROCEDURE Rules and Procedures... Default. If the subject individual fails to file a petition for a hearing, or fails to appear at a hearing...
Sloof, R.; Oosterbeek, H.; Sonnemans, J.
Theory predicts that default breach remedies are immaterial whenever contracting costs are negligible. Some experimental studies, however, suggest that in practice default rules do matter, as they may affect parties' preferences over contract terms. This paper presents results from an experiment
... 12 Banks and Banking 5 2010-01-01 2010-01-01 false Default. 508.8 Section 508.8 Banks and Banking OFFICE OF THRIFT SUPERVISION, DEPARTMENT OF THE TREASURY REMOVALS, SUSPENSIONS, AND PROHIBITIONS WHERE A CRIME IS CHARGED OR PROVEN § 508.8 Default. If the subject individual fails to file a petition for a...
Shabir, I.; Iqbal, R.; Khan, S.U.; Munir, K.; Nazir, A.
Tuberculosis remains the single highest contributor to the world's morbidity and mortality. Early diagnosis and prompt treatment is essential to prevent its transmission. To see the treatment response of anti tuberculosis drugs in smear negative patients and study the predictors of culture positive among smear negative tuberculosis patients. Ninety four sputum smear negative patients clinically and radiologically suggestive of tuberculosis were selected. These patients were put on anti tuberculosis drugs without waiting for their culture results. They were then followed for 8 months to see their treatment outcome. A total of 94 smear negative patients were selected and given anti tuberculosis treatment. Of these 37(39%) were culture positive and 57(61%) were culture negative. Of the 37 culture positive patients 36(97%) showed clinical or radiological improvement as compared to 46(81%) out of 57 in culture negative cases. Symptoms of cough with sputum production was significantly associated with culture positivity. On x-ray chest moderate lesion with diffuse infiltration was more common finding in 64% while extensive and cavitatory lesion was seen in 24% of all cases. Association of extensive and cavitatory lesion were seen in culture positive group. Response to anti tuberculosis drugs in sputum smear negative tubercolosis suspects was found to be effective in majority of the patients. Cough, sputum and extensive cavitatory lung lesion were the predictors of culture positive cases. There is need to train physicians on the use of anti tuberculosis therapy in smear negative suspected pulmonary tuberculosis cases, especially if they have productive cough and cavitatory lung lesions. (author)
Fosgaard, Toke Reinholt
Based on a dice rolling task where participants can cheat on the outcome, this paper asks if default answers change dishonesty? The paper finds that various default answers have asymmetric effects. Compared to not having a default answer at all, providing a low default answer, or adding the expec......Based on a dice rolling task where participants can cheat on the outcome, this paper asks if default answers change dishonesty? The paper finds that various default answers have asymmetric effects. Compared to not having a default answer at all, providing a low default answer, or adding...
... 17 Commodity and Securities Exchanges 1 2010-04-01 2010-04-01 false Setting aside of default. 12... aside of default. (a) Default order not final. In order to prevent injustice or for good cause shown, and on such conditions as may be appropriate, a non-final default order (including any award therein...
... 46 Shipping 8 2010-10-01 2010-10-01 false Remedies after default. 298.41 Section 298.41 Shipping... Defaults and Remedies, Reporting Requirements, Applicability of Regulations § 298.41 Remedies after default... governing remedies after a default, which relate to our rights and duties, the rights and duties of the...
... 24 Housing and Urban Development 2 2010-04-01 2010-04-01 false Date of default. 241.840 Section... § 241.840 Date of default. In computing loan insurance benefits, the date of default shall be considered... of the lender's acceleration of the debt because of the borrower's default under the first...
... 24 Housing and Urban Development 2 2010-04-01 2010-04-01 false Notice of default. 232.850 Section....850 Notice of default. (a) If the default is not cured within the 30 day grace period, as defined in... default. (b) The lender shall give notice in writing to the Commissioner of the failure of the borrower to...
... 24 Housing and Urban Development 2 2010-04-01 2010-04-01 false Notice of default. 241.850 Section... § 241.850 Notice of default. (a) If the default is not cured within the 30 day grace period, as defined... such default. (b) The lender shall give notice in writing to the Commissioner of the failure of the...
... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Procedure for default 1349... MANAGEMENT TERMINATION OF CONTRACTS Termination for Default 1349.402-3 Procedure for default No action relating to a default termination, including issuance of a show cause letter, cure notice, or notice of...
I. V. Belovа
Full Text Available The study was conducted in order to evaluate the efficiency of adding immobilized probiotic biologically active food supplement of LB-Complex L to integral treatment of pulmonary tuberculosis. Changes of colon microorganism community in pulmonary tuberculosis patients including those with multiple drug resistance were studied in two groups of patients: receiving only basic treatment and basic treatment with the immobolized probiotic of LB-Complex L as a food supplement. The algorithm of probiotic intake has been offered with the consideration of pharmacodynamics of anti-tuberculosis drugs. The offered algorithm proved to be effective for prevention of disorders in microorganism community, enhancement of adherence to treatment, reduction of frequency, severity and duration of side effects to anti-tuberculosis drugs.
Tuladhar, Anil Man; Snaphaan, Liselore; Shumskaya, Elena; Rijpkema, Mark; Fernandez, Guillén; Norris, David G; de Leeuw, Frank-Erik
The pathophysiology of episodic memory dysfunction after infarction is not completely understood. It has been suggested that infarctions located anywhere in the brain can induce widespread effects causing disruption of functional networks of the cortical regions. The default mode network, which includes the medial temporal lobe, is a functional network that is associated with episodic memory processing. We investigated whether the default mode network activity is reduced in stroke patients compared to healthy control subjects in the resting state condition. We assessed the whole brain network properties during resting state functional MRI in 21 control subjects and 20 'first-ever' stroke patients. Patients were scanned 9-12 weeks after stroke onset. Stroke lesions were located in various parts of the brain. Independent component analyses were conducted to identify the default mode network and to compare the group differences of the default mode network. Furthermore, region-of-interest based analysis was performed to explore the functional connectivity between the regions of the default mode network. Stroke patients performed significantly worse than control subjects on the delayed recall score on California verbal learning test. We found decreased functional connectivity in the left medial temporal lobe, posterior cingulate and medial prefrontal cortical areas within the default mode network and reduced functional connectivity between these regions in stroke patients compared with controls. There were no significant volumetric differences between the groups. These results demonstrate that connectivity within the default mode network is reduced in 'first-ever' stroke patients compared to control subjects. This phenomenon might explain the occurrence of post-stroke cognitive dysfunction in stroke patients.
Full Text Available Background: The treatment outcome "default" under Revised National Tuberculosis Control Program (RNTCP is a patient who after treatment initiation has interrupted treatment consecutively for more than 2 months. Aims: To assess the timing, characteristics and distribution of the reasons for default with relation to some sociodemographic variables among new sputum-positive (NSP tuberculosis (TB patients in Darjeeling District, West Bengal. Settings and Design: A case-control study was conducted in three tuberculosis units (TUs of Darjeeling from August′2011 to December′2011 among NSP TB patients enrolled for treatment in the TB register from 1 st Qtr′09 to 2 nd Qtr′10. Patients defaulted from treatment were considered as "cases" and those completed treatment as "controls" (79 cases and 79 controls. Materials and Methods: The enrolled cases and controls were interviewed by the health workers using a predesigned structured pro-forma. Statistical Analysis Used: Logistic regression analysis, odds ratios (OR, adjusted odds ratios (AOR. Results: 75% of the default occurred in the intensive phase (IP; 54.24% retrieval action was done within 1 day during IP and 75% within 1 week during continuation phase (CP; cent percent of the documented retrieval actions were undertaken by the contractual TB program staffs. Most commonly cited reasons for default were alcohol consumption (29.11%, adverse effects of drugs (25.32%, and long distance of DOT center (21.52%. In the logistic regression analysis, the factors independently associated were consumption of alcohol, inadequate knowledge about TB, inadequate patient provider interaction, instances of missed doses, adverse reactions of anti-TB drugs, Government Directly Observed Treatment (DOT provider and smoking. Conclusions: Most defaults occurred in the intensive phase; pre-treatment counseling and initial home visit play very important role in this regard. Proper counseling by health care workers in
Akwaa-Sekyi, Ellis Kofi
Full Text Available The initiation, funding, servicing and monitoring of loans by financial intermediaries has been done without regard to some critical factors which could have averted the likelihood of default. The study aimed at measuring the extent that owner-specific, borrower-specific, loan and lender-specific characteristics could determine the probability of loan default. The study used logistic regression for 224 business customers of a bank in Ghana from its nation-wide branches. The study found that owner’s extra income (ownership characteristics, multiple borrowing, diversion of loan purpose (borrower characteristics, loan price, loan purpose, loan age, repayment plan (loan characteristics and underfunding (lender characteristics significantly determined the probability of business loan default. The overall model predicted up to 78.5% of variations in the likelihood of default. The hierarchy of strong determinants given by their odd ratios were loan purpose (47.9 times, underfunding (19.2 times, diversion of loan purpose (11.7 times multiple borrowing (9.4 times and owner’s extra income (8.2 times. The study can conclude that financial intermediaries should be wary of the credit granting process taking cognisance of ownership, borrower, loan and lender characteristics especially the significant predictors. Combining quantitative and qualitative variables as determinants of default could be considered in future.
Vatansever, D; Menon, D K; Manktelow, A E; Sahakian, B J; Stamatakis, E A
Initially described as task-induced deactivations during goal-directed paradigms of high attentional load, the unresolved functionality of default mode regions has long been assumed to interfere with task performance. However, recent evidence suggests a potential default mode network involvement in fulfilling cognitive demands. We tested this hypothesis in a finger opposition paradigm with task and fixation periods which we compared with an independent resting state scan using functional magnetic resonance imaging and a comprehensive analysis pipeline including activation, functional connectivity, behavioural and graph theoretical assessments. The results indicate task specific changes in the default mode network topography. Behaviourally, we show that increased connectivity of the posterior cingulate cortex with the left superior frontal gyrus predicts faster reaction times. Moreover, interactive and dynamic reconfiguration of the default mode network regions' functional connections illustrates their involvement with the task at hand with higher-level global parallel processing power, yet preserved small-world architecture in comparison with rest. These findings demonstrate that the default mode network does not disengage during this paradigm, but instead may be involved in task relevant processing. Copyright © 2015 Elsevier Inc. All rights reserved.
Feldhütter, Peter; Nielsen, Mads Stenbo
We present a new estimation approach that allows us to extract from spreads in synthetic credit markets the contribution of systematic and idiosyncratic default risk to total default risk. Using an extensive dataset of 90,600 credit default swap and collateralized debt obligation (CDO) tranche...... spreads on the North American Investment Grade CDX index, we conduct an empirical analysis of an intensity-based model for correlated defaults. Our results show that systematic default risk is an explosive process with low volatility, while idiosyncratic default risk is more volatile but less explosive...
Mirowsky, John; Ross, Catherine E
Education has a large and increasing impact on health in America. This paper examines one reason why. Education gives individuals the ability to override the default American lifestyle. The default lifestyle has three elements: displacing human energy with mechanical energy, displacing household food production with industrial food production, and displacing health maintenance with medical dependency. Too little physical activity and too much food produce imperceptibly accumulating pathologies. The medical industry looks for products and services that promise to soften the consequences but do not eliminate the underlying pathologies. This "secondary prevention" creates pharmacologic accumulation: prolonging the use of medications, layering them, and accruing their side effects and interactions. Staying healthy depends on recognizing the risks of the default lifestyle. Overriding it requires insight, knowledge, critical analysis, long-range strategic thinking, personal agency, and self-direction. Education develops that ability directly and indirectly, by way of creative work and a sense of controlling one's own life. © American Sociological Association 2015.
Vatansever, Deniz; Menon, David K; Stamatakis, Emmanuel A
Concurrent with mental processes that require rigorous computation and control, a series of automated decisions and actions govern our daily lives, providing efficient and adaptive responses to environmental demands. Using a cognitive flexibility task, we show that a set of brain regions collectively known as the default mode network plays a crucial role in such "autopilot" behavior, i.e., when rapidly selecting appropriate responses under predictable behavioral contexts. While applying learned rules, the default mode network shows both greater activity and connectivity. Furthermore, functional interactions between this network and hippocampal and parahippocampal areas as well as primary visual cortex correlate with the speed of accurate responses. These findings indicate a memory-based "autopilot role" for the default mode network, which may have important implications for our current understanding of healthy and adaptive brain processing.
Bares, R; Khalid, N; Daniel, H; Dittmann, H; Reimold, M; Gallwitz, B; Schmotzer, C
Hypothyroidism is an adverse effect of certain anti-tuberculosis drugs. This is a prospective study of the frequency and possible pathomechanisms associated with hypothyroidism due to second-line treatment of multidrug-resistant tuberculosis. Fifty human immunodeficiency virus negative patients and 20 controls were included. All participants underwent ultrasonography of the thyroid and measurement of thyroid stimulating hormone (TSH). TSH levels were checked every 3 months. If hypothyroidism was present, T3, T4 and thyroid peroxidase autoantibodies were measured, and imaging extended to scintigraphy and repeated ultrasonography. Before treatment, 7 patients (14%) and 1 control (5%) were hypothyreotic. During the first 6 months of treatment, TSH levels increased in 41 patients (82%), 39 (78%) had values above the normal range and 19 (38%) had overt hypothyroidism. As none of the patients had signs of autoimmune thyroiditis, interaction with anti-tuberculosis drugs was assumed to be the cause of hypothyroidism. Nine patients died during treatment, all of whom had developed hypothyroidism. In seven, the metabolic situation at their death was known, and they had become euthyreotic following levothyroxine substitution. TSH levels should be checked before initiating anti-tuberculosis treatment and after 3 and 6 months to start timely replacement of levothyroxine. Further studies are needed to elucidate the exact pathomechanism involved in hypothyroidism and whether hypothyroidism can be used as predictor of treatment failure.
Sarangi, S S; Dutt, D
In India in 2010, 14.1% of retreatment of TB patients' treatment outcome was 'default'. Since 2002, in Paschim Midnapur District (West Bengal), it has been around 15-20%. To determine the timing, characteristics and risk factors associated with default among retreatment TB patients on DOTS. It was a case control study, conducted in six TB units (TU) of Paschim Midnapur District, which were selected by simple random sampling. Data was collected from treatment records of TUs/DTC. Data was also collected through interviews of the patients using the same pre-tested semi-structured questionnaire from 87 defaulters and 86 consecutively registered non-defaulters registered in first quarter, 2009 to second quarter, 2010. Median duration of treatment taken before default was 121 days (inter-quartile range of 64-176 days). Median number of doses of treatment taken before default was 36 (inter -quartile range of 26-63 doses). No retrieval action was documented in 57.5% cases. Retrieval was done between 0-7 days of missed doses in 29.9% cases. Multiple logistic regression analysis indicated the following important risk factors for default at 95% confidence interval: male-sex limit: [aOR 3.957 (1.162-13.469)], alcoholic inebriation[ aOR6.076 (2.088-17.675)], distance from DOT centre [aOR 4.066 (1.675-9.872)], number of missed doses during treatment [aOR 1.849 (1.282-2.669)] and no initial home visit [aOR 10.607 (2.286 -49.221)]. In Paschim Midnapur district, default of retreatment TB occurs mostly after a few doses in continuation phase. Initial home visit, patient provider meeting, retrieval action, community-based treatment as per RNTCP guidelines are required to uplift the programme.
Augustin, Patrick; Sokolovski, Valeri; Subrahmanyam, Marti G.
We provide a comprehensive analysis of the determinants of trading in the sovereign credit default swaps (CDS) market, using weekly data for single-name sovereign CDS from October 2008 to September 2015. We describe the anatomy of the sovereign CDS market, derive a law of motion for gross positions...
Tuladhar, A.M.; Snaphaan, L.J.A.E.; Shumskaya, A.N.; Rijpkema, M.J.P.; Fernandez, G.S.E.; Norris, D.G.; Leeuw, F.E. de
The pathophysiology of episodic memory dysfunction after infarction is not completely understood. It has been suggested that infarctions located anywhere in the brain can induce widespread effects causing disruption of functional networks of the cortical regions. The default mode network, which
Kentucky Council on Postsecondary Education, 2016
As college costs continue to rise, student loan default and repayment are issues of increasing concern to students and families, colleges and universities, and state and federal governments. Helping students borrow responsibly and manage their debt are vitally important to maintaining college access and affordability and increasing the education…
While Minnesota undergraduates are more likely to take out student loans, they are substantially less likely than their peers nationally to default on federal student loans. Fifty-four percent of Minnesota undergraduates took out student loans in 2007-2008, compared to 39 percent of undergraduates across the U.S. Minnesota undergraduates were also…
Nielsen, Jesper Kjær; Christensen, Mads Græsbøll; Jensen, Søren Holdt
Joint fundamental frequency and model order esti- mation is an important problem in several applications. In this paper, a default estimation algorithm based on a minimum of prior information is presented. The algorithm is developed in a Bayesian framework, and it can be applied to both real...
The model is applied to primary data from a survey of 200 small scale entrepreneurs in the Upper West Region of Ghana. Results show that enterprise size, interest rate, loan duration, level of profit and loan amount are the simultaneous determinants of probability and rate of default. The study recommends that the National ...
In their analysis of a representative sample from the Prescribing Observatory for Mental Health in the UK health services, Paton et al found that 92% of patients with borderline personality disorder (BPD) received prescriptions for psychotropic medications. Although international guidelines recommend pharmacotherapy for comorbid psychiatric disorders whenever necessary, 82% of the UK BPD patients without such comorbid conditions nevertheless received pharmacotherapy "by default," mostly off-label polypharmacy without adequate psychiatric controls for effectiveness and tolerability. Business as usual? Bad care? International practice guidelines for the treatment of BPD all recommend evidence-based psychological treatment whenever possible (especially manualized psychotherapy like dialectical behavior therapy, schema-focused therapy, mentalization-based treatment, transference-focused psychotherapy) as the first-choice treatment. © Copyright 2015 Physicians Postgraduate Press, Inc.
Wu, Minjie; Andreescu, Carmen; Butters, Meryl A; Tamburo, Robert; Reynolds, Charles F; Aizenstein, Howard
The brain's default-mode network has been the focus of intense research. This study characterizes the default-mode network activity in late-life depression and the correlation of the default-mode network activity changes with the white-matter hyperintensities burden. We hypothesized that elderly depressed subjects would have altered default-mode network activity, which would correlate with the increased white-matter hyperintensities burden. Twelve depressed subjects (mean Hamilton Depression Rating Scale 19.8±4.1, mean age 70.5±4.9) and 12 non-depressed, comparison subjects (mean age 69±6.5) were included. Functional magnetic resonance imaging (fMRI) data were collected while subjects performed a low cognitive load, event-related task. We compared the default-mode network activity in these groups (including depressed subjects pre- and post-antidepressant treatment). We analyzed the resting connectivity patterns of the posterior cingulate cortex. Deconvolution was used to evaluate the correlation of resting-state connectivity scores with the white-matter hyperintensities burden. Compared with non-depressed elderly, depressed subjects pretreatment had decreased connectivity in the subgenual anterior cingulate cortex and increased connectivity in the dorsomedial prefrontal cortex and the orbito-frontal cortex. The abnormal connectivity was significantly correlated with the white-matter hyperintensities burden. Remitted elderly depressed subjects had improved functional connectivity compared to pretreatment, although alterations persisted in the anterior cingulate and the prefrontal cortex when remitted elderly depressed subjects were compared with non-depressed elderly. Our study provides evidence for altered default-mode network connectivity in late-life depression. The correlation between white-matter hyperintensities burden and default-mode network connectivity emphasizes the role of vascular changes in late-life depression etiopathogenesis. Copyright © 2011
This study was conducted to determine the vaccination default rate and vaccine schedule that is most frequently defaulted. It also documented reasons for the defaults and suggested ways of minimising them. The immunization status of 174 children aged 9-11 months were determined by interviewing mothers regarding ...
... 17 Commodity and Securities Exchanges 1 2010-04-01 2010-04-01 false Setting aside of default. 10... PRACTICE Disposition Without Full Hearing § 10.94 Setting aside of default. In order to prevent injustice and on such conditions as may be appropriate, (a) the Commission may at any time set aside a default...
... 24 Housing and Urban Development 2 2010-04-01 2010-04-01 false Date of default. 232.840 Section 232.840 Housing and Urban Development Regulations Relating to Housing and Urban Development (Continued....840 Date of default. In computing loan insurance benefits, the date of default shall be considered as...
... 48 Federal Acquisition Regulations System 3 2010-10-01 2010-10-01 false Termination for default... of Provisions And Clauses 252.237-7007 Termination for default. As prescribed in 237.7003(b), use the following clause: Termination for Default (DEC 1991) (a) This clause supplements and is in addition to the...
..., Sequence 1] RIN 9000-AL45 Federal Acquisition Regulation; Termination for Default Reporting AGENCIES... terminations for cause or default and defective cost or pricing data, into the Past Performance Information... defective cost or pricing data and terminations for cause or default into the FAPIIS module of the PPIRS...
... 24 Housing and Urban Development 2 2010-04-01 2010-04-01 false Date of default. 220.811 Section... and Obligations-Projects Insured Project Improvement Loans § 220.811 Date of default. For the purposes of §§ 220.800 et seq., the date of default shall be considered as: (a) The date of the first...
Bouckaert, J.M.C.; Degryse, H.A.
We offer a social-welfare comparison of the two most prominent default options – opt in and opt out – using a two-period model of localized competition. We demonstrate that when consumers stick to the default option, the prevailing default policy shapes firms' ability to collect and use customer
... 24 Housing and Urban Development 2 2010-04-01 2010-04-01 false Definition of default. 232.830... Insurance § 232.830 Definition of default. (a) If the borrower fails to make any payments due under or... default for the purposes of this subpart. (b) The failure to perform any other covenant under the note or...
... 42 Public Health 1 2010-10-01 2010-10-01 false What events constitute default? 23.28 Section 23.28 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES PERSONNEL NATIONAL HEALTH... default? The following events will constitute defaults of the loan agreement: (a) Failure to make full...
... 17 Commodity and Securities Exchanges 1 2010-04-01 2010-04-01 false Obtaining default order. 10.93... Disposition Without Full Hearing § 10.93 Obtaining default order. When a respondent has failed to (a) file an... enter findings and conclusions and a default order against that respondent based upon the matters set...
... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Brewer in default. 25.173... OF THE TREASURY LIQUORS BEER Tax on Beer Prepayment of Tax § 25.173 Brewer in default. (a) When a... the brewer is otherwise in default in payment of tax under § 25.164, beer may not be removed for...
... 48 Federal Acquisition Regulations System 4 2010-10-01 2010-10-01 false Procedure for default. 449.402-3 Section 449.402-3 Federal Acquisition Regulations System DEPARTMENT OF AGRICULTURE CONTRACT MANAGEMENT TERMINATION OF CONTRACTS Termination for Default 449.402-3 Procedure for default. In addition to...
... 12 Banks and Banking 6 2010-01-01 2010-01-01 false Retirement in event of default. 615.5280... Dividends § 615.5280 Retirement in event of default. (a) When the debt of a holder of eligible borrower... association or agricultural credit association is in default, such institution may, but shall not be required...
... 48 Federal Acquisition Regulations System 1 2010-10-01 2010-10-01 false Termination for default... Amended 22.1023 Termination for default. As provided by the Act, any contractor failure to comply with the requirements of the contract clauses related to the Act may be grounds for termination for default (see...
... 24 Housing and Urban Development 2 2010-04-01 2010-04-01 false Definition of default. 220.810... Contract Rights and Obligations-Projects Insured Project Improvement Loans § 220.810 Definition of default... note or security instrument and such default continues for a period of 30 days, the note or security...
... 29 Labor 9 2010-07-01 2010-07-01 false Consequences of default. 2570.5 Section 2570.5 Labor... ERISA Section 502(i) § 2570.5 Consequences of default. For prohibited transaction penalty proceedings... administrative law judge may set aside a default entered under this provision where there is proof of defective...
... 24 Housing and Urban Development 2 2010-04-01 2010-04-01 false Definition of default. 241.830... § 241.830 Definition of default. (a) If the borrower fails to make any payments due under or provided to be paid by the terms of the note or security instrument, the note shall be considered in default for...
... 7 Agriculture 11 2010-01-01 2010-01-01 false Borrowers in default. 1717.653 Section 1717.653..., Loans, and Guarantees by Electric Borrowers § 1717.653 Borrowers in default. Any borrower not in... the required action, then, upon written notice from RUS, the borrower shall be in default of its RUS...
... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Procedure for default. 1449.402-3 Section 1449.402-3 Federal Acquisition Regulations System DEPARTMENT OF THE INTERIOR CONTRACT MANAGEMENT TERMINATION OF CONTRACTS Termination for Default 1449.402-3 Procedure for default. In...
... 27 Alcohol, Tobacco Products and Firearms 2 2010-04-01 2010-04-01 false Default, prepayment of tax... Payment of Taxes on Tobacco Products § 40.166 Default, prepayment of tax required. Where a check or money... tax due thereunder, or where a manufacturer is otherwise in default in payment of tax on tobacco...
... 24 Housing and Urban Development 2 2010-04-01 2010-04-01 false Notice of default. 220.812 Section... and Obligations-Projects Insured Project Improvement Loans § 220.812 Notice of default. (a) If the default as defined in § 220.810 is not cured within the 30 day grace period, the lender shall, within 30...
Baele, L.T.M.; Farooq, Moazzam; Ongena, S.R.G.
We compare default rates on conventional and Islamic loans using a comprehensive monthly dataset from Pakistan that follows more than 150,000 loans over the period 2006:04 to 2008:12. We find robust evidence that the default rate on Islamic loans is less than half the default rate on conventional
Mothersill, Omar; Tangney, Noreen; Morris, Derek W; McCarthy, Hazel; Frodl, Thomas; Gill, Michael; Corvin, Aiden; Donohoe, Gary
Resting-state functional magnetic resonance imaging (rs-fMRI) has repeatedly shown evidence of altered functional connectivity of large-scale networks in schizophrenia. The relationship between these connectivity changes and behaviour (e.g. symptoms, neuropsychological performance) remains unclear. Functional connectivity in 27 patients with schizophrenia or schizoaffective disorder, and 25 age and gender matched healthy controls was examined using rs-fMRI. Based on seed regions from previous studies, we examined functional connectivity of the default, cognitive control, affective and attention networks. Effects of symptom severity and theory of mind performance on functional connectivity were also examined. Patients showed increased connectivity between key nodes of the default network including the precuneus and medial prefrontal cortex compared to controls (pdefault regions within the patient group (pdefault hyper-connectivity in schizophrenia spectrum patients and reveals an association between altered default connectivity and positive symptom severity. As a novel find, this study also shows that default connectivity is correlated to and predictive of theory of mind performance. Extending these findings by examining the effects of emerging social cognition treatments on both default connectivity and theory of mind performance is now an important goal for research. Copyright © 2016 Elsevier B.V. All rights reserved.
Daniels, Randell W.
Default management practices and their relationship to the student loan default rate in public two-year community colleges was the focus of this investigation. Five research questions regarding written default management plans, default management practices, process management, accountability, and other factors impacting default guided the study.…
Puliga, Michelangelo; Caldarelli, Guido; Battiston, Stefano
Credit Default Swaps (CDS) spreads should reflect default risk of the underlying corporate debt. Actually, it has been recognized that CDS spread time series did not anticipate but only followed the increasing risk of default before the financial crisis. In principle, the network of correlations among CDS spread time series could at least display some form of structural change to be used as an early warning of systemic risk. Here we study a set of 176 CDS time series of financial institutions from 2002 to 2011. Networks are constructed in various ways, some of which display structural change at the onset of the credit crisis of 2008, but never before. By taking these networks as a proxy of interdependencies among financial institutions, we run stress-test based on Group DebtRank. Systemic risk before 2008 increases only when incorporating a macroeconomic indicator reflecting the potential losses of financial assets associated with house prices in the US. This approach indicates a promising way to detect systemic instabilities.
Puliga, Michelangelo; Caldarelli, Guido; Battiston, Stefano
Credit Default Swaps (CDS) spreads should reflect default risk of the underlying corporate debt. Actually, it has been recognized that CDS spread time series did not anticipate but only followed the increasing risk of default before the financial crisis. In principle, the network of correlations among CDS spread time series could at least display some form of structural change to be used as an early warning of systemic risk. Here we study a set of 176 CDS time series of financial institutions from 2002 to 2011. Networks are constructed in various ways, some of which display structural change at the onset of the credit crisis of 2008, but never before. By taking these networks as a proxy of interdependencies among financial institutions, we run stress-test based on Group DebtRank. Systemic risk before 2008 increases only when incorporating a macroeconomic indicator reflecting the potential losses of financial assets associated with house prices in the US. This approach indicates a promising way to detect systemic instabilities.
Adelia Surya Pratiwi
Full Text Available This paper is motivated by the fact that emerging market assets size has been expanding and trying to use sovereign debt market as part of capital market as main research focus. It is highlighting the distinction between default and non-default determinants and examining their significance in explaining emerging market sovereign bond yield spread. Using Cross-Sectional Fixed-Effect Panel Estimator, we found that both default (as proxied by Credit Rating and Outlook Index and non-default (as proxied by 3-month Fed Funds Futures determinants has significant explanatory power to sovereign bond yield spread. Extensively, we also found the significance to add volatility of 3-month Fed Funds Futures and Fed Target Rate basis and volatility of advanced stock markets as variables to stand for non-default determinants in the model. The significance of the latter model is strengthened by higher forecasting as well as indicates the significant role of US market to emerging market sovereign bond market.
Full Text Available In today’s rapidly evolving financial markets, risk management offers different techniques in order to implement an efficient system against market risk. Probability of default (PD is an essential part of business intelligence and customer relation management systems in the financial institutions. Recent studies indicates that underestimating this important component, and also the loss given default (LGD, might threaten the stability and smooth running of the financial markets. From the perspective of risk management, the result of predictive accuracy of the estimated probability of default is more valuable than the standard binary classification: credible or non credible clients. The Basle II Accord recognizes the methods of reducing credit risk and also PD and LGD as important components of advanced Internal Rating Based (IRB approach.
Hart, Joanna; Halpern, Scott D.
Purpose of review Default options dramatically influence the behavior of decision makers and may serve as effective decision support tools in the ICU. Their use in medicine has increased in an effort to improve efficiency, reduce errors, and harness the potential of healthcare technology. Recent findings Defaults often fall short of their predicted influence when employed in critical care settings as quality improvement interventions. Investigations reporting the use of defaults are often limited by variations in the relative effect across sites. Preimplementation experiments and long-term monitoring studies are lacking. Summary Defaults in the ICU may help or harm patients and clinical efficiency depending on their format and use. When constructing and encountering defaults, providers should be aware of their powerful and complex influences on decision making. Additional evaluations of the appropriate creation of healthcare defaults and their resulting intended and unintended consequences are needed. PMID:25203352
Jensen, Thais Lærkholm; Lando, David; Medhat, Mamdouh
The Basel II/III and CRD IV Accords reduce capital charges on bank loans to smaller firms by assuming that the default probabilities of smaller firms are less sensitive to macroeconomic cycles. We test this assumption in a default intensity framework using a large sample of bank loans to private...... Danish firms. We find that controlling only for size, the default probabilities of small firms are, in fact, less cyclical than the default probabilities of large firms. However, accounting for firm characteristics other than size, we find that the default probabilities of small firms are equally...... cyclical or even more cyclical than the default probabilities of large firms. These results hold using a multiplicative Cox model as well as an additive Aalen model with time-varying coefficients....
Barbose, Galen; Goldman, Charles; Neenan, Bernie
In designing default service for competitive retail markets, demand response has been an afterthought at best. But that may be changing, as states that initiated customer choice in the past five to seven years reach an important juncture in retail market design and consider an RTP-type default service for large commercial and industrial customers. The authors describe the experience to date with RTP as a default service, focusing on its role as an instrument for cultivating price-responsive demand. (author)
Gu Wei; Chu Jianxin
In order to detecting the magnetic leakage fields of the wire rope defaults, a transducer made up of the fluxgate array is designed, and a series of the characteristic values of wire rope defaults signals are defined. By processing the characteristic signals, the LF or LMA of wire rope are distinguished, and the default extent is estimated. The experiment results of the new method for detecting the wire rope faults are introduced
Vatansever, Deniz; Menon, David K; Manktelow, Anne E; Sahakian, Barbara J; Stamatakis, Emmanuel A
The default mode network (DMN) has been traditionally assumed to hinder behavioral performance in externally focused, goal-directed paradigms and to provide no active contribution to human cognition. However, recent evidence suggests greater DMN activity in an array of tasks, especially those that involve self-referential and memory-based processing. Although data that robustly demonstrate a comprehensive functional role for DMN remains relatively scarce, the global workspace framework, which implicates the DMN in global information integration for conscious processing, can potentially provide an explanation for the broad range of higher-order paradigms that report DMN involvement. We used graph theoretical measures to assess the contribution of the DMN to global functional connectivity dynamics in 22 healthy volunteers during an fMRI-based n-back working-memory paradigm with parametric increases in difficulty. Our predominant finding is that brain modularity decreases with greater task demands, thus adapting a more global workspace configuration, in direct relation to increases in reaction times to correct responses. Flexible default mode regions dynamically switch community memberships and display significant changes in their nodal participation coefficient and strength, which may reflect the observed whole-brain changes in functional connectivity architecture. These findings have important implications for our understanding of healthy brain function, as they suggest a central role for the DMN in higher cognitive processing. The default mode network (DMN) has been shown to increase its activity during the absence of external stimulation, and hence was historically assumed to disengage during goal-directed tasks. Recent evidence, however, implicates the DMN in self-referential and memory-based processing. We provide robust evidence for this network's active contribution to working memory by revealing dynamic reconfiguration in its interactions with other networks
Full Text Available Poor treatment adherence leading to risk of drug resistance, treatment failure, relapse, death and persistent infectiousness remains an impediment to the tuberculosis control programmes. The objective of the study was to identify predictors of default among new smear positive TB patients registered for treatment to suggest possible interventions to set right the problems to sustain and enhance the programme performance.Twenty districts selected from six states were assigned to six strata formed, considering the geographic, socio-cultural and demographic setup of the area. New smear positive patients registered for treatment in two consecutive quarters during III quarter 2004 to III quarter 2005 formed the retrospective study cohort. Case control analysis was done including defaulted patients as "cases" and equal number of age and sex matched patients completing treatment as "controls". The presence and degree of association between default and determinant factors was computed through univariate and multivariate logistic regression analysis. Data collection was through patient interviews using pre-tested semi structured questionnaire and review of treatment related records. Information on a wide range of socio demographic and patient related factors was obtained. Among the 687 defaulted and equal numbers of patients in completed group, 389 and 540 patients respectively were satisfactorily interviewed. In the logistic regression analysis, factors independently associated with default were alcoholism [AOR-1.72 (1.23-2.44], illiteracy [AOR-1.40 (1.03-1.92], having other commitments during treatment [AOR-3.22 (1.1-9.09], inadequate knowledge of TB [AOR-1.88(1.35-2.63], poor patient provider interaction [AOR-1.72(1.23-2.44], lack of support from health staff [AOR-1.93(1.41-2.64], having instances of missed doses [AOR-2.56(1.82-3.57], side effects to anti TB drugs [AOR-2.55 (1.87-3.47] and dissatisfaction with services provided [AOR-1.73 (1
Leonidov, A. V.; Rumyantsev, E. L.
Systemic risks of default contagion in the Russian interbank market are investigated. The analysis is based on considering the bow-tie structure of the weighted oriented graph describing the structure of the interbank loans. A probabilistic model of interbank contagion explicitly taking into account the empirical bow-tie structure reflecting functionality of the corresponding nodes (borrowers, lenders, borrowers and lenders simultaneously), degree distributions and disassortativity of the interbank network under consideration based on empirical data is developed. The characteristics of contagion-related systemic risk calculated with this model are shown to be in agreement with those of explicit stress tests.
Rodriquez, Luis I; Smaka, Todd J; Mahla, Michael; Epstein, Richard H
In the United States, anesthesia information management systems (AIMS) are well established, especially within academic practices. Many hospitals are replacing their stand-alone AIMS during migration to an enterprise-wide electronic health record. This presents an opportunity to review choices made during the original implementation, based on actual usage. One area amenable to this informatics approach is the configuration in the AIMS of quick buttons for typical drug doses. The use of such short cuts, as opposed to manual typing of doses, simplifies and may improve the accuracy of drug documentation within the AIMS. We analyzed administration data from 3 different institutions, 2 of which had empirically configured default doses, and one in which defaults had not been set up. Our first hypothesis was that most (ie, >50%) of drugs would need at least one change to the existing defaults. Our second hypothesis was that for most (>50%) drugs, the 4 most common doses at the site lacking defaults would be included among the most common doses at the 2 sites with defaults. If true, this would suggest that having default doses did not affect the typical administration behavior of providers. The frequency distribution of doses for all drugs was determined, and the 4 most common doses representing at least 5% of total administrations for each drug were identified. The appropriateness of the current defaults was determined by the number of changes (0-4) required to match actual usage at the 2 hospitals with defaults. At the institution without defaults, the most frequent doses for the 20 most commonly administered drugs were compared with the default doses at the other institutions. At the 2 institutions with defaults, 84.7% and 77.5% of drugs required at least 1 change in the default drug doses (P default drug doses, 100% of the 20 most commonly administered doses (representing ≥5% of use for that drug) were included in the most commonly administered doses at the other 2
Hayes, Scott M; Salat, David H; Verfaellie, Mieke
There is substantial overlap between the brain regions supporting episodic memory and the default network. However, in humans, the impact of bilateral medial temporal lobe (MTL) damage on a large-scale neural network such as the default mode network is unknown. To examine this issue, resting fMRI was performed with amnesic patients and control participants. Seed-based functional connectivity analyses revealed robust default network connectivity in amnesia in cortical default network regions such as medial prefrontal cortex, posterior medial cortex, and lateral parietal cortex, as well as evidence of connectivity to residual MTL tissue. Relative to control participants, decreased posterior cingulate cortex connectivity to MTL and increased connectivity to cortical default network regions including lateral parietal and medial prefrontal cortex were observed in amnesic patients. In contrast, somatomotor network connectivity was intact in amnesic patients, indicating that bilateral MTL lesions may selectively impact the default network. Changes in default network connectivity in amnesia were largely restricted to the MTL subsystem, providing preliminary support from MTL amnesic patients that the default network can be fractionated into functionally and structurally distinct components. To our knowledge, this is the first examination of the default network in amnesia.
Forero, Aura; Romero, Eduardo
This document presents a proposal devoted to improve the detection of the default mode network (DMN) in resting state functional magnetic resonance imaging in noisy conditions caused by head movement. The proposed approach is inspired by the hierarchical treatment of information, in particular at the level of the brain basal ganglia. Essentially, the fact that information must be selected and reduced suggests propagation of information in the Central Nervous System (CNS) is anisotropic. Under this hypothesis, the reconstruction of information of activation should follow an anisotropic pattern. In this work, an anisotropic filter is used to recover the DMN that is perturbed by simulated motion artifacts. Results obtained show this approach outperforms the state-of-the-art methods by 5.93% PSNR.
Parameter setting to non-default proceeds from subset to superset languages. In syllable structure and using tree notation, development implies the introduction of marked structure, with structural complexity. The second half of the paper focuses on second language acquisition, where parameters (can) undergo re-setting.
Sampaio, Adriana; Soares, José Miguel; Coutinho, Joana; Sousa, Nuno; Gonçalves, Óscar F
Recent neuroimaging studies have provided evidence that different dimensions of human personality may be associated with specific structural neuroanatomic correlates. Identifying brain correlates of a situation-independent personality structure would require evidence of a stable default mode of brain functioning. In this study, we investigated the correlates of the Big Five personality dimensions (Extraversion, Neuroticism, Openness/Intellect, Agreeableness, and Conscientiousness) and the default mode network (DMN). Forty-nine healthy adults completed the NEO-Five Factor. The results showed that the Extraversion (E) and Agreeableness (A) were positively correlated with activity in the midline core of the DMN, whereas Neuroticism (N), Openness (O), and Conscientiousness (C) were correlated with the parietal cortex system. Activity of the anterior cingulate cortex was positively associated with A and negatively with C. Regions of the parietal lobe were differentially associated with each personality dimension. The present study not only confirms previous functional correlates regarding the Big Five personality dimensions, but it also expands our knowledge showing the association between different personality dimensions and specific patterns of brain activation at rest.
In Toronto, various agencies, all claiming to represent the best interests of consumers, have taken very different positions on the limits that should be placed on suppliers of standard electricity service, due to an unexpected effect of Ontario's market design. The debate has polarized into either support for the Market Design Committee's recommendations restricting local companies' distribution of electricity to one of passing on the spot market price to their standard customers or the view that municipal utilities should be permitted to enter into contracts for power in order to supply the needs of their standard service customers. The Independent Power Producers' Society of Ontario (IPPSO) takes the position that its member companies should have direct access to the default supply market and not to be forced to deal solely with the spot market to reach this market sector. This default market is expected to be the largest potential end use market in Ontario for the power produced and/or sold by IPPSO members. It is expected to be 70% of the total Ontario wholesale electricity market for many years to come
Nuijten, Michèle B; Wetzels, Ruud; Matzke, Dora; Dolan, Conor V; Wagenmakers, Eric-Jan
In order to quantify the relationship between multiple variables, researchers often carry out a mediation analysis. In such an analysis, a mediator (e.g., knowledge of a healthy diet) transmits the effect from an independent variable (e.g., classroom instruction on a healthy diet) to a dependent variable (e.g., consumption of fruits and vegetables). Almost all mediation analyses in psychology use frequentist estimation and hypothesis-testing techniques. A recent exception is Yuan and MacKinnon (Psychological Methods, 14, 301-322, 2009), who outlined a Bayesian parameter estimation procedure for mediation analysis. Here we complete the Bayesian alternative to frequentist mediation analysis by specifying a default Bayesian hypothesis test based on the Jeffreys-Zellner-Siow approach. We further extend this default Bayesian test by allowing a comparison to directional or one-sided alternatives, using Markov chain Monte Carlo techniques implemented in JAGS. All Bayesian tests are implemented in the R package BayesMed (Nuijten, Wetzels, Matzke, Dolan, & Wagenmakers, 2014).
Lakshmanan, Divya; Werngren, Jim; Jose, Leny; Suja, K P; Nair, Mangalam S; Varma, R Luxmi; Mundayoor, Sathish; Hoffner, Sven; Kumar, R Ajay
Many plants are used in Ayurveda for the treatment of tuberculosis. Our aim was to examine if these plants possess any specific molecule that inhibits Mycobacterium tuberculosis. One of them, Kaempferia galanga, yielded an anti-TB molecule, ethyl p-methoxycinnamate (EPMC). By resazurin microtitre assay (REMA), EPMC was shown to inhibit M. tuberculosis H37Ra, H37Rv, drug susceptible and multidrug resistant (MDR) clinical isolates (MIC 0.242-0.485mM). No cross resistance was observed to any standard anti-TB drugs in the MDR strains. The compound did not inhibit any prototype bacteria tested. EPMC seems to be a potential anti-TB lead molecule. Copyright © 2011 Elsevier B.V. All rights reserved.
... Reporting of Greenhouse Gases: Notice of Data Availability; Default Emission Factors for Semiconductor... the public draft default emission factors for semiconductor manufacturing refined process categories... reporting, EPA proposed semiconductor manufacturers estimate emissions using default emission factors for...
Background: Obstetric procedures are carried out to reduce or completely eliminate maternal and perinatal morbidities and mortalities. Objectives: is to determine the mode of presentation and materno-foctal outcome in defaulters of obstetric procedures, the reasons for defaulting the obstetric procedurcs and to institute ...
Jang, Seung-cheol; Jung, Won-dea; Ha, Jae-joo; Jin, Young-ho
Both performing and validating a detailed risk analysis of a complex system are costly and time-consuming undertakings. With the increased use of probabilistic risk analysis (PRA) in regulatory decision making, both PRA practitioners (usually, licensees) and regulators have generally favored the use of defaults because they can greatly facilitate the process of performing a PRA in the first place as well as the process of reviewing and verifying the PRA. The use of defaults can also ensure more uniform standards of PRA quality. However, different regulatory agencies differ in their approaches to the use of default values, and the implications of these differences are not yet widely understood. Moreover, large heterogeneity among licensees makes it difficult to set suitable defaults. This paper will focus on the effect of default values on estimates of risk. In particular, the following questions will be explored: ''How should defaults be set?''; and ''What are the implications of choosing different default values?'' Some insights on the effects of different levels of conservatism in setting defaults will be provided. This can help decision makers evaluate the levels of safety likely to result from regulatory decisions
... 29 Labor 9 2010-07-01 2010-07-01 false Consequences of default. 2570.114 Section 2570.114 Labor Regulations Relating to Labor (Continued) EMPLOYEE BENEFITS SECURITY ADMINISTRATION, DEPARTMENT OF LABOR... ERISA Section 502(c)(6) § 2570.114 Consequences of default. For 502(c)(6) civil penalty proceedings...
... 25 Indians 1 2010-04-01 2010-04-01 false Penalties on default. 101.15 Section 101.15 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR FINANCIAL ACTIVITIES LOANS TO INDIANS FROM THE REVOLVING LOAN FUND § 101.15 Penalties on default. Unless otherwise provided in the loan agreement between...
... 29 Labor 9 2010-07-01 2010-07-01 false Consequences of default. 2570.94 Section 2570.94 Labor Regulations Relating to Labor (Continued) EMPLOYEE BENEFITS SECURITY ADMINISTRATION, DEPARTMENT OF LABOR... ERISA Section 502(c)(5) § 2570.94 Consequences of default. For 502(c)(5) civil penalty proceedings, this...
... 29 Labor 9 2010-07-01 2010-07-01 false Consequences of default. 2570.64 Section 2570.64 Labor Regulations Relating to Labor (Continued) EMPLOYEE BENEFITS SECURITY ADMINISTRATION, DEPARTMENT OF LABOR... ERISA Section 502(c)(2) § 2570.64 Consequences of default. For 502(c)(2) civil penalty proceedings, this...
... 49 Transportation 1 2010-10-01 2010-10-01 false Default upon failure to answer. 31.10 Section 31.10 Transportation Office of the Secretary of Transportation PROGRAM FRAUD CIVIL REMEDIES § 31.10 Default upon failure to answer. (a) If the defendant does not answer within the time prescribed in § 31.9...
P. Houweling (Patrick); A.C.F. Vorst (Ton)
textabstractAbstract: In this paper we compare market prices of credit default swaps with model prices. We show that a simple reduced form model with a constant recovery rate outperforms the market practice of directly comparing bonds' credit spreads to default swap premiums. We find that the
Ishitani, Terry T.; McKitrick, Sean A.
As more undergraduates have taken out loans to attend college, the number of borrowers who fail to repay their student loans has increased. While previous research has focused on students' likelihood to default, this study employed institutional cohort default rates (CDRs) as an outcome variable. Using Integrated Postsecondary Education Data…
Dinner, Isaac; Johnson, Eric J.; Goldstein, Daniel G.; Liu, Kaiya
Default options exert an influence in areas as varied as retirement program design, organ donation policy, and consumer choice. Past research has offered potential reasons why no-action defaults matter: (a) effort, (b) implied endorsement, and (c) reference dependence. The first two of these explanations have been experimentally demonstrated, but…
Hillman, Nicholas W.
This study examines the institutional factors associated with student loan default. When a college has more than 30% of its students default on their loans, then the institution faces federal sanctions that could make them ineligible from participating in the federal student loan program. Using Integrated Postsecondary Education Data System…
Regelski, Thomas A.
This paper explores the effects and problems of one highly influential default setting of the "normal style template" of music education and proposes some alternatives. These do not require abandoning all traditional templates for school music. But re-setting the default settings does depend on reconsidering the promised function of…
... 29 Labor 9 2010-07-01 2010-07-01 false Consequences of default. 2570.134 Section 2570.134 Labor Regulations Relating to Labor (Continued) EMPLOYEE BENEFITS SECURITY ADMINISTRATION, DEPARTMENT OF LABOR... ERISA Section 502(c)(7) § 2570.134 Consequences of default. For 502(c)(7) civil penalty proceedings...
Hillman, Nicholas W.
This study updates and expands the literature on student loan default. By applying multilevel regression to the Beginning Postsecondary Students survey, four key findings emerge. First, attending proprietary institutions is strongly associated with default, even after accounting for students' socioeconomic and academic backgrounds. Second,…
The U.S. Department of Education estimates that 20 percent of community college students default on their student loan obligations (compared with 14.7 percent of all student loan borrowers), and that number is rising. What can community college financial officers do to keep their default numbers low? In this article, Heather Boerner describes the…
... 29 Labor 9 2010-07-01 2010-07-01 false Consequences of default. 2570.164 Section 2570.164 Labor Regulations Relating to Labor (Continued) EMPLOYEE BENEFITS SECURITY ADMINISTRATION, DEPARTMENT OF LABOR... ERISA Section 502(c)(8) § 2570.164 Consequences of default. For 502(c)(8) civil penalty proceedings...
McKibben, Bryce; La Rocque, Matthew; Cochrane, Debbie
Student loan default, defined as federal loan borrowers' failure to make any payments for at least 270 days, is an issue of increasing importance to community colleges and their students. This report takes a unique look at student loan default at nine community colleges across the nation, and how those colleges are working to help students avoid…
Department of Education, Washington, DC. Default Management Div.
This guide provides information to help postsecondary schools and guaranty agencies (GAs) understand how a cohort default rate is calculated, review backup data, submit challenges to GAs and/or Direct Loan Servicing Centers (DLSC), and understand the response from the GA and/or DLSC. A cohort default rate includes Federal Family Education Loan…
... 7 Agriculture 12 2010-01-01 2010-01-01 false Defaults by borrower. 1779.75 Section 1779.75 Agriculture Regulations of the Department of Agriculture (Continued) RURAL UTILITIES SERVICE, DEPARTMENT OF AGRICULTURE (CONTINUED) WATER AND WASTE DISPOSAL PROGRAMS GUARANTEED LOANS § 1779.75 Defaults by borrower. (a...
The use of Cohort Default Rate (CDR) as the primary measure of student loan defaults among undergraduates was investigated. The study used data extracted from the National Student Loan Data System (NSLDS), quantitative analysis of Likert-scale survey responses from 153 student financial aid professionals on proposed changes to present metrics and…
This makes the study on probability of a customer defaulting very useful while analyzing the credit risk policies. In this paper, we use a raw data set that contains demographic information about the borrowers. The data sets have been used to identify which risk factors associated with the borrowers contribute towards default.
... to reduce default rate and loan diversions since members can serve as watch dog to each other. Banks should also prevent unnecessary delay in loan disbursement to allow for timely use of the loan. Banks should also explore the Agricultural credit guarantee scheme (ACGS) to offset part of the risk in case of default.
Goda, Gopi Shah; Manchester, Colleen Flaherty
We study the effect of incorporating heterogeneity into default rules by examining the choice between retirement plans at a firm that transitioned from a defined benefit (DB) to a defined contribution (DC) plan. The default plan for existing employees varied discontinuously depending on their age. Employing regression discontinuity techniques,…
Mantini, Dante; Gerits, Annelis; Nelissen, Koen; Durand, Jean-Baptiste; Joly, Olivier; Simone, Luciano; Sawamura, Hiromasa; Wardak, Claire; Orban, Guy A; Buckner, Randy L; Vanduffel, Wim
Human neuroimaging has revealed a specific network of brain regions-the default-mode network (DMN)-that reduces its activity during goal-directed behavior. So far, evidence for a similar network in monkeys is mainly indirect, since, except for one positron emission tomography study, it is all based on functional connectivity analysis rather than activity increases during passive task states. Here, we tested whether a consistent DMN exists in monkeys using its defining property. We performed a meta-analysis of functional magnetic resonance imaging data collected in 10 awake monkeys to reveal areas in which activity consistently decreases when task demands shift from passive tasks to externally oriented processing. We observed task-related spatially specific deactivations across 15 experiments, implying in the monkey a functional equivalent of the human DMN. We revealed by resting-state connectivity that prefrontal and medial parietal regions, including areas 9/46d and 31, respectively, constitute the DMN core, being functionally connected to all other DMN areas. We also detected two distinct subsystems composed of DMN areas with stronger functional connections between each other. These clusters included areas 24/32, 8b, and TPOC and areas 23, v23, and PGm, respectively. Such a pattern of functional connectivity largely fits, but is not completely consistent with anatomical tract tracing data in monkeys. Also, analysis of afferent and efferent connections between DMN areas suggests a multisynaptic network structure. Like humans, monkeys increase activity during passive epochs in heteromodal and limbic association regions, suggesting that they also default to internal modes of processing when not actively interacting with the environment.
Vasile George MARICA
Full Text Available This paper investigates contagion in international credit markets through the use of a novel jump detection technique proposed by Chan and Maheuin (2002. This econometrical methodology is preferred because it is non-linear by definition and not a subject to volatility bias. Also, the identified jumps in CDS premiums are considered as outliers positioned beyond any stochastic movement that can and is already modelled through well-known linear analysis. Though contagion is hard to define, we show that extreme discrete movements in default probabilities inferred from CDS premiums can lead to sound economic conclusions about the risk profile of sovereign nations in international bond markets. We find evidence of investor sentiment clustering for countries with unstable political regimes or that are engaged in armed conflict. Countries that have in their recent history faced currency or financial crises are less vulnerable to external unexpected shocks. First we present a brief history of sovereign defaults with an emphasis on their increased frequency and geographical reach, as financial markets become more and more integrated. We then pass to a literature review of the most important definitions for contagion, and discuss what quantitative methods are available to detect the presence of contagion. The paper continues with the details for the methodology of jump detection through non-linear modelling and its use in the field of contagion identification. In the last sections we present the estimation results for simultaneous jumps between emerging markets CDS and draw conclusions on the difference of behavior in times of extreme movement versus tranquil periods.
Katz, Yuri A.
Diffusion in a linear potential in the presence of position-dependent killing is used to mimic a default process. Different assumptions regarding transport coefficients, initial conditions, and elasticity of the killing measure lead to diverse models of bankruptcy. One “stylized fact” is fundamental for our consideration: empirically default is a rather rare event, especially in the investment grade categories of credit ratings. Hence, the action of killing may be considered as a small parameter. In a number of special cases we derive closed-form expressions for the entire term structure of the cumulative probability of default, its hazard rate, and intensity. Comparison with historical data on aggregate global corporate defaults confirms the validity of the perturbation method for estimations of long-term probability of default for companies with high credit quality. On a single company level, we implement the derived formulas to estimate the one-year likelihood of default of Enron on a daily basis from August 2000 to August 2001, three months before its default, and compare the obtained results with forecasts of traditional structural models.
Fair, Damien A; Cohen, Alexander L; Dosenbach, Nico U F; Church, Jessica A; Miezin, Francis M; Barch, Deanna M; Raichle, Marcus E; Petersen, Steven E; Schlaggar, Bradley L
In recent years, the brain's "default network," a set of regions characterized by decreased neural activity during goal-oriented tasks, has generated a significant amount of interest, as well as controversy. Much of the discussion has focused on the relationship of these regions to a "default mode" of brain function. In early studies, investigators suggested that, the brain's default mode supports "self-referential" or "introspective" mental activity. Subsequently, regions of the default network have been more specifically related to the "internal narrative," the "autobiographical self," "stimulus independent thought," "mentalizing," and most recently "self-projection." However, the extant literature on the function of the default network is limited to adults, i.e., after the system has reached maturity. We hypothesized that further insight into the network's functioning could be achieved by characterizing its development. In the current study, we used resting-state functional connectivity MRI (rs-fcMRI) to characterize the development of the brain's default network. We found that the default regions are only sparsely functionally connected at early school age (7-9 years old); over development, these regions integrate into a cohesive, interconnected network.
Lando, David; Medhat, Mamdouh; Nielsen, Mads Stenbo
We consider additive intensity (Aalen) models as an alternative to the multiplicative intensity (Cox) models for analyzing the default risk of a sample of rated, nonfinancial U.S. firms. The setting allows for estimating and testing the significance of time-varying effects. We use a variety...... of model checking techniques to identify misspecifications. In our final model, we find evidence of time-variation in the effects of distance-to-default and short-to-long term debt. Also we identify interactions between distance-to-default and other covariates, and the quick ratio covariate is significant....... None of our macroeconomic covariates are significant....
Steenkamp, Juliana; Lategan, Ronette
Full text: In 2008, 4.7% South African children under five years suffered from moderate wasting and 23.9% from moderate stunting. Intervention strategies in the public health care system allow for targeted supplementation of children with moderate malnutrition and/or growth failure for three to six months or less if catch-up growth is established. Earlier research among HIV-infected adults on antiretroviral therapy showed that only about 50% of adults could be retained in a nutrition supplementation programme. The aim of this research was to determine default rates of children with moderate malnutrition on a targeted supplementary feeding programme, using Ready-to-use Supplementary Food (RUSF) as home treatment and to explore possible associations between socio-demographic and nutritional factors and defaulting. Between September 2012 and August 2013, a prospective controlled trial was performed in three provinces of South Africa. Children between 12 and 60 months, classified as moderately malnourished, were purposefully selected by dieticians for inclusion in the study, after informed consent was obtained from the legal guardian. Ethical approval was obtained from the Research Ethics Committee, NNMU. In this study defaulting refers to failure to return to the programme after admission, or more than two consecutive absences. Participants had to attend five follow-up sessions, during which children were weighed, measured and data collected in a structured questionnaire. At each visit participants received RUSF as treatment for moderate malnutrition. Parents received a stipend to encourage return. Data were analyzed using PASW (Predictive Analytics SoftWare) by SPSS (Version 21). Frequencies and percentages were used to describe categorical data. Comparisons of means were performed using t-tests. Chi-square tests and two-tailed Pearson correlations were used to describe and test associations and correlations between variables. A p-level ≤0.05 was considered
these epidemics, many challenges remain. Antiretroviral and anti-TB drug resistance pose considerable threats to the control of these epidemics.[4,5]. The breakdown in HIV/TB control within prisons is another emerging threat.[6,7] We describe one of the first reports of combined antiretroviral and anti-TB drug resistance ...
Guo, Wenbin; Liu, Feng; Chen, Jindong; Wu, Renrong; Li, Lehua; Zhang, Zhikun; Chen, Huafu; Zhao, Jingping
Previous studies on brain function alterations associated with antipsychotic treatment for schizophrenia have produced conflicting results because they used short treatment periods and different designs. Resting-state functional magnetic resonance imaging scans were obtained from 17 drug-free patients with recurrent schizophrenia and 24 healthy controls. The patients were treated with olanzapine for 6 months and were scanned at three time points (baseline, 6 weeks of treatment and 6 months of treatment). Network homogeneity was used to analyze the imaging data to examine default-mode network homogeneity alterations associated with antipsychotic treatment. Compared with the controls, the patients at baseline showed increased network homogeneity in the bilateral precuneus and decreased network homogeneity in the bilateral middle temporal gyrus. Network homogeneity values in the bilateral precuneus decreased, and network homogeneity values in the left superior medial prefrontal cortex and the right middle temporal gyrus increased in patients administered olanzapine as antipsychotic treatment. By contrast, network homogeneity values in the left middle temporal gyrus remained unchanged in patients after treatment. This study provides evidence that antipsychotic treatment with olanzapine modulates the default-mode network homogeneity in schizophrenia. These findings contribute to the understanding of antipsychotic treatment effects on brain functions.
...) PROGRAM REGULATIONS (CONTINUED) GENERAL Business and Industrial Loan Program § 1980.470 Defaults by... explanation of the loan history, an evaluation and scope of the proposed study and the need should be included...
Biagini, Francesca; Cretarola, Alessandra
We study the local risk-minimization approach for defaultable claims with random recovery at default time, seen as payment streams on the random interval [0,τ∧T], where T denotes the fixed time-horizon. We find the pseudo-locally risk-minimizing strategy in the case when the agent information takes into account the possibility of a default event (local risk-minimization with G-strategies) and we provide an application in the case of a corporate bond. We also discuss the problem of finding a pseudo-locally risk-minimizing strategy if we suppose the agent obtains her information only by observing the non-defaultable assets.
Phillips, Jonathan; Cushman, Fiery
The capacity for representing and reasoning over sets of possibilities, or modal cognition, supports diverse kinds of high-level judgments: causal reasoning, moral judgment, language comprehension, and more. Prior research on modal cognition asks how humans explicitly and deliberatively reason about what is possible but has not investigated whether or how people have a default, implicit representation of which events are possible. We present three studies that characterize the role of implicit representations of possibility in cognition. Collectively, these studies differentiate explicit reasoning about possibilities from default implicit representations, demonstrate that human adults often default to treating immoral and irrational events as impossible, and provide a case study of high-level cognitive judgments relying on default implicit representations of possibility rather than explicit deliberation.
.... Specifically, the audit focused on contracts terminated either for default or convenience and determined whether the contract terminations could have been averted based on information available before contract award...
Mehmet Ali Soytaş
Full Text Available Using the fixed-point theorem, sovereign default models are solved by numerical value function iteration and calibration methods, which due to their computational constraints, greatly limits the models' quantitative performance and foregoes its country-specific quantitative projection ability. By applying the Hotz-Miller estimation technique (Hotz and Miller, 1993- often used in applied microeconometrics literature- to dynamic general equilibrium models of sovereign default, one can estimate the ex-ante default probability of economies, given the structural parameter values obtained from country-specific business-cycle statistics and relevant literature. Thus, with this technique we offer an alternative solution method to dynamic general equilibrium models of sovereign default to improve upon their quantitative inference ability.
Zhang, Minghui; He, Jianmin; Li, Shouwei
This paper studies the default risk contagion in banking systems based on a dynamic network model with two different kinds of lenders' selecting mechanisms, namely, endogenous selecting (ES) and random selecting (RS). From sensitivity analysis, we find that higher risk premium, lower initial proportion of net assets, higher liquid assets threshold, larger size of liquidity shocks, higher proportion of the initial investments and higher Central Bank interest rates all lead to severer default risk contagion. Moreover, the autocorrelation of deposits and lenders' selecting probability have non-monotonic effects on the default risk contagion, and the effects differ under two mechanisms. Generally, the default risk contagion is much severer under RS mechanism than that of ES, because the multi-money-center structure generated by ES mechanism enables borrowers to borrow from more liquid banks with lower interest rates.
Bluhm, Robyn L; Clark, C Richard; McFarlane, Alexander C; Moores, Kathryn A; Shaw, Marnie E; Lanius, Ruth A
The default network exhibits correlated activity at rest and has shown decreased activation during performance of cognitive tasks. There has been little investigation of changes in connectivity of this network during task performance. In this study, we examined task-related modulation of connectivity between two seed regions from the default network posterior cingulated cortex (PCC) and medial prefrontal cortex (mPFC) and the rest of the brain in 12 healthy adults. The purpose was to determine (1) whether connectivity within the default network differs between a resting state and performance of a cognitive (working memory) task and (2) whether connectivity differs between these nodes of the default network and other brain regions, particularly those implicated in cognitive tasks. There was little change in connectivity with the other main areas of the default network for either seed region, but moderate task-related changes in connectivity occurred between seed regions and regions outside the default network. For example, connectivity of the mPFC with the right insula and the right superior frontal gyrus decreased during task performance. Increased connectivity during the working memory task occurred between the PCC and bilateral inferior frontal gyri, and between the mPFC and the left inferior frontal gyrus, cuneus, superior parietal lobule, middle temporal gyrus and cerebellum. Overall, the areas showing greater correlation with the default network seed regions during task than at rest have been previously implicated in working memory tasks. These changes may reflect a decrease in the negative correlations occurring between the default and task-positive networks at rest. Copyright © 2010 Wiley-Liss, Inc.
S. Mori; K. Kitsukawa; M. Hisakado
We show how to analyze and interpret the correlation structures, the conditional expectation values and correlation coefficients of exchangeable Bernoulli random variables. We study implied default distributions for the iTraxx-CJ tranches and some popular probabilistic models, including the Gaussian copula model, Beta binomial distribution model and long-range Ising model. We interpret the differences in their profiles in terms of the correlation structures. The implied default distribution h...
Ferguson, Michael A.; Lopez-Larson, Melissa; Yurgelun-Todd, Deborah
Abstract Functional imaging studies have shown reduced activity within the default mode network during attention-demanding tasks. The network circuitry underlying this suppression remains unclear. Proposed hypotheses include an attentional switch in the right anterior insula and reciprocal inhibition between the default mode and attention control networks. We analyzed resting state blood oxygen level dependent (BOLD) data from 1278 subjects from 26 sites and constructed whole-brain maps of functional connectivity between 7266 regions of interest (ROIs) covering the gray matter at ∼5 mm resolution. ROIs belonging to the default mode network and attention control network were identified based on correlation to six published seed locations. Spatial heterogeneity of correlation between the default mode and attention control networks was observed, with smoothly varying gradients in every hub of both networks that ranged smoothly from weakly but significantly anticorrelated to positively correlated. Such gradients were reproduced in 3 separate groups of subjects. Anticorrelated subregions were identified in major hubs of both networks. Between-network connectivity gradients strengthen with age during late adolescence and early adulthood, with associated sharpening of the boundaries of the default mode network, integration of the insula and cingulate with frontoparietal attentional regions, and decreasing correlation between the default mode and attention control networks with age. PMID:22076305
Ter Minassian, Aram; Ricalens, Emmanuel; Humbert, Stanislas; Duc, Flavie; Aubé, Christophe; Beydon, Laurent
Few studies have explored the effect of acute pain on attentional networks and on the default mode network. Moreover, these studies convey conflicting results, seemingly caused by design. To reassess this issue, we studied 20 healthy subjects with functional magnetic resonance imaging while delivering painful electric shocks. The design was purposely constructed to separate rest, anticipation, and pain perception. We found that default mode network activity in response to pain was biphasic. It deactivated during anticipation when the dorsal attentional network was activated. During pain perception, the default mode network was activated, as were attentional networks. The left posterior fusiform gyrus showed the same dynamics as the default mode network, and its activity was negatively correlated to the subject's pain intensity rating. The associative pregenual anterior cingulate cortex seemed to play a key role in these coactivations. These results concur with data from the literature showing that enhanced pain perception results in greater default mode network activity and that the anticorrelation between the default mode network and the dorsal attentional network disappears in chronic pain patients. Copyright © 2012 Wiley Periodicals, Inc., a Wiley company.
Jang, S.C.; Ha, J.J.; Jung, W.D.; Jeong, K.S.; Han, S.H.
Both performing and validating a detailed risk analysis of a complex system are costly and time-consuming undertakings. With the increased use of probabilistic safety analysis (PSA) in regulatory decision making, both regulated parties and regulators have generally favored the use of defaults, because they can greatly facilitate the process of performing a PSA in the first place as well as the process of reviewing and verifying the PSA. The use of defaults may also ensure more uniform standards of PSA quality. However, regulatory agencies differ in their approaches to the use of default values, and the implications of these differences are not yet well understood. Moreover, large heterogeneity among licensees makes it difficult to set suitable defaults. This study focus on the development of model for setting defaults in order to achieve more applicability of risk-informed regulation. In particular, explored are the effects of different levels of conservatism in setting defaults, and their implications for the crafting of regularity incentives. (author). 17 refs., 1 tab
Spreng, R Nathan; DuPre, Elizabeth; Selarka, Dhawal; Garcia, Juliana; Gojkovic, Stefan; Mildner, Judith; Luh, Wen-Ming; Turner, Gary R
Substantial neuroimaging evidence suggests that spontaneous engagement of the default network impairs performance on tasks requiring executive control. We investigated whether this impairment depends on the congruence between executive control demands and internal mentation. We hypothesized that activation of the default network might enhance performance on an executive control task if control processes engage long-term memory representations that are supported by the default network. Using fMRI, we scanned 36 healthy young adult humans on a novel two-back task requiring working memory for famous and anonymous faces. In this task, participants (1) matched anonymous faces interleaved with anonymous face, (2) matched anonymous faces interleaved with a famous face, or (3) matched a famous faces interleaved with an anonymous face. As predicted, we observed a facilitation effect when matching famous faces, compared with anonymous faces. We also observed greater activation of the default network during these famous face-matching trials. The results suggest that activation of the default network can contribute to task performance during an externally directed executive control task. Our findings provide evidence that successful activation of the default network in a contextually relevant manner facilitates goal-directed cognition. Copyright © 2014 the authors 0270-6474/14/3414108-07$15.00/0.
Liston, Conor; Chen, Ashley C.; Zebley, Benjamin D.; Drysdale, Andrew T.; Gordon, Rebecca; Leuchter, Bruce; Voss, Henning U.; Casey, B.J.; Etkin, Amit; Dubin, Marc J.
Background Repetitive transcranial magnetic stimulation (TMS) of the dorsolateral prefrontal cortex (DLPFC) is an established treatment for depression, but its underlying mechanism of action remains unknown. Abnormalities in two large-scale neuronal networks—the frontoparietal central executive network (CEN) and the medial prefrontal-medial parietal default mode network (DMN)—are consistent findings in depression and potential therapeutic targets for TMS. Here, we assessed the impact of TMS on activity in these networks and their relation to treatment response. Methods We used resting state functional magnetic resonance imaging (rs-fMRI) to measure functional connectivity within and between the DMN and CEN in 17 depressed patients, before and after a five-week course of TMS. Motivated by prior reports, we focused on connectivity seeded from the DLPFC and the subgenual cingulate, a key region closely aligned with the DMN in depression. Connectivity was also compared to a cohort of 35 healthy controls. Results Prior to treatment, functional connectivity in depressed patients was abnormally elevated within the DMN and diminished within the CEN, and connectivity between these two networks was altered. TMS normalized depression-related subgenual hyperconnectivity in the DMN but did not alter connectivity in the CEN. TMS also induced anticorrelated connectivity between the DLPFC and medial prefrontal DMN nodes. Baseline subgenual connectivity predicted subsequent clinical improvement. Conclusions TMS selectively modulates functional connectivity both within and between the CEN and DMN, and modulation of subgenual cingulate connectivity may play an important mechanistic role in alleviating depression. The results also highlight potential neuroimaging biomarkers for predicting treatment response. PMID:24629537
Full Text Available BACKGROUND: Low adherence to multidrug therapy against leprosy (MDT is still an important obstacle of disease control, and may lead to remaining sources of infection, incomplete cure, irreversible complications, and multidrug resistance. METHODOLOGY/PRINCIPAL FINDING: We performed a population-based study in 78 municipalities in Tocantins State, central Brazil, and applied structured questionnaires on leprosy-affected individuals. We used two outcomes for assessment of risk factors: defaulting (not presenting to health care center for supervised treatment for >12 months; and interruption of MDT. In total, 28/936 (3.0% patients defaulted, and 147/806 (18.2% interrupted MDT. Defaulting was significantly associated with: low number of rooms per household (OR = 3.43; 0.98-9.69; p = 0.03; moving to another residence after diagnosis (OR = 2.90; 0.95-5.28; p = 0.04; and low family income (OR = 2.42; 1.02-5.63: p = 0.04. Interruption of treatment was associated with: low number of rooms per household (OR = 1.95; 0.98-3.70; p = 0.04; difficulty in swallowing MDT drugs (OR = 1.66; 1.03-2.63; p = 0.02; temporal non-availability of MDT at the health center (OR = 1.67; 1.11-2.46; p = 0.01; and moving to another residence (OR = 1.58; 95% confidence interval: 1.03-2.40; p = 0.03. Logistic regression identified temporal non-availability of MDT as an independent risk factor for treatment interruption (adjusted OR = 1.56; 1.05-2.33; p = 0.03, and residence size as a protective factor (adjusted OR = 0.89 per additional number of rooms; 0.80-0.99; p = 0.03. Residence size was also independently associated with defaulting (adjusted OR = 0.67; 0.52-0.88; p = 0.003. CONCLUSIONS: Defaulting and interruption of MDT are associated with some poverty-related variables such as family income, household size, and migration. Intermittent problems of drug supply need to be resolved, mainly on the municipality level. MDT producers should consider oral drug formulations that may
Ezechi, Oliver Chukwujekwu; Petterson, Karen Odberg; Gbajabiamila, Titilola A; Idigbe, Ifeoma Eugenia; Kuyoro, Olutunmike; Ujah, Innocent Achaya Otobo; Ostergren, Per Olof
Increasingly evidence is emerging from south East Asia, southern and east Africa on the burden of default to follow up care after a positive cervical cancer screening/diagnosis, which impacts negatively on cervical cancer prevention and control. Unfortunately little or no information exists on the subject in the West Africa sub region. This study was designed to determine the proportion of and predictors and reasons for default from follow up care after positive cervical cancer screen. Women who screen positive at community cervical cancer screening using direct visual inspection were followed up to determine the proportion of default and associated factors. Multivariate logistic regression was used to determine independent predictors of default. One hundred and eight (16.1%) women who screened positive to direct visual inspection out of 673 were enrolled into the study. Fifty one (47.2%) out of the 108 women that screened positive defaulted from follow-up appointment. Women who were poorly educated (OR: 3.1, CI: 2.0 - 5.2), or lived more than 10 km from the clinic (OR: 2.0, CI: 1.0 - 4.1), or never screened for cervical cancer before (OR: 3.5, CI:3:1-8.4) were more likely to default from follow-up after screening positive for precancerous lesion of cervix . The main reasons for default were cost of transportation (48.6%) and time constraints (25.7%). The rate of default was high (47.2%) as a result of unaffordable transportation cost and limited time to keep the scheduled appointment. A change from the present strategy that involves multiple visits to a "see and treat" strategy in which both testing and treatment are performed at a single visit is recommended.
Full Text Available The impact of a stress scenario of default events on the loss distribution of a credit portfolio can be assessed by determining the loss distribution conditional on these events. While it is conceptually easy to estimate loss distributions conditional on default events by means of Monte Carlo simulation, it becomes impractical for two or more simultaneous defaults as then the conditioning event is extremely rare. We provide an analytical approach to the calculation of the conditional loss distribution for the CreditRisk + portfolio model with independent random loss given default distributions. The analytical solution for this case can be used to check the accuracy of an approximation to the conditional loss distribution whereby the unconditional model is run with stressed input probabilities of default (PDs. It turns out that this approximation is unbiased. Numerical examples, however, suggest that the approximation may be seriously inaccurate but that the inaccuracy leads to overestimation of tail losses and, hence, the approach errs on the conservative side.
van Erp, Sara; Mulder, Joris; Oberski, Daniel L
Bayesian structural equation modeling (BSEM) has recently gained popularity because it enables researchers to fit complex models and solve some of the issues often encountered in classical maximum likelihood estimation, such as nonconvergence and inadmissible solutions. An important component of any Bayesian analysis is the prior distribution of the unknown model parameters. Often, researchers rely on default priors, which are constructed in an automatic fashion without requiring substantive prior information. However, the prior can have a serious influence on the estimation of the model parameters, which affects the mean squared error, bias, coverage rates, and quantiles of the estimates. In this article, we investigate the performance of three different default priors: noninformative improper priors, vague proper priors, and empirical Bayes priors-with the latter being novel in the BSEM literature. Based on a simulation study, we find that these three default BSEM methods may perform very differently, especially with small samples. A careful prior sensitivity analysis is therefore needed when performing a default BSEM analysis. For this purpose, we provide a practical step-by-step guide for practitioners to conducting a prior sensitivity analysis in default BSEM. Our recommendations are illustrated using a well-known case study from the structural equation modeling literature, and all code for conducting the prior sensitivity analysis is available in the online supplemental materials. (PsycINFO Database Record (c) 2017 APA, all rights reserved).
behind terrifying images of memory of mutilation. rejection and exclusion from society (I). It leads to progressi.ve physical. psychological and social disabilities because of the stigma associated with the. I Faculty of Health Sciences . Alemava University. P.O. Box 138. Alernava. 'Depart~ent of Microbiology and Parasitology.
Full Text Available In order to reduce the exchange-rate risk, banks in emerging markets are typically denominating their loans in foreign currencies. However, in the event of a substantial depreciation of the local currency, the payment ability of a foreign-currency borrower may be reduced significantly, exposing the lender to additional default risk. This paper analyses how the exchange-rate risk of foreign currency loans spills over into default risk. We show that in an economy where foreign currency loans are a dominant source of financing economic activity, depreciation of the local currency establishes a negative feedback mechanism that leads to higher default probabilities, reduced credit supply, and reduced growth. This finding has some important implications that may be of special interest for regulators and market participants in emerging economies.
Mori, Shintaro; Kitsukawa, Kenji; Hisakado, Masato
We show how to analyze and interpret the correlation structures, the conditional expectation values and correlation coefficients of exchangeable Bernoulli random variables. We study implied default distributions for the iTraxx-CJ tranches and some popular probabilistic models, including the Gaussian copula model, Beta binomial distribution model and long-range Ising model. We interpret the differences in their profiles in terms of the correlation structures. The implied default distribution has singular correlation structures, reflecting the credit market implications. We point out two possible origins of the singular behavior.
Li, Danyang; Hawley, Zackary; Schnier, Kurt
This research utilizes a laboratory experiment to evaluate the effectiveness of alternative public policies targeted at increasing the rate of deceased donor organ donation. The experiment includes treatments across different default choices and organ allocation rules inspired by the donor registration systems applied in different countries. Our results indicate that the opt-out with priority rule system generates the largest increase in organ donation relative to an opt-in only program. However, sizeable gains are achievable using either a priority rule or opt-out program separately, with the opt-out rule generating approximately 80% of the benefits achieved under a priority rule program. PMID:24135615
Full Text Available This paper presents a study of the nonmonotonic consequence relation which models the skeptical reasoning formalised by constrained default logic. The nonmonotonic skeptical consequence relation is defined using the sequent calculus axiomatic system. We study the formal properties desirable for a good nonmonotonic relation: supraclassicality, cut, cautious monotony, cumulativity, absorption, distribution.
Sun, Huihui; Chen, Ying; Zhao, Xiaohu; Wang, Xiangbin; Jiang, Yuanxi; Wu, Ping; Tang, Yinhan; Meng, Qingwei; Xu, Shuchang
Abnormal processing of esophageal sensation at the level of the central nervous system has been proven to be involved in gastroesophageal reflux disease (GERD). However, most studies were focused on the possible functions of perceptual processing related network during task status, little attention has been paid to default mode network, which has been manifested to be important in the pathogenesis of many diseases. In our study, we compared the brain activity characteristic in GERD patients with the healthy subjects (HS) at baseline, looking for whether activities of default mode network were abnormal in GERD patients and attempting to identify their possible roles in GERD. In present study, fractional amplitude of low-frequency fluctuation was adopted to detect the brain activities at baseline. Group-level analyses were conducted by one-sample t test within groups (voxel thresholds were p42, corrected P90, corrected Pdefault mode network such as medial superior frontal gyrus, precuneus, posterior cingulate gyrus, etc. However, the activities of precuneus and posterior cingulate gyrus were significantly lower in GERD patients than those in the HS. The activities of precuneus and posterior cingulate gyrus of default mode network in GERD patients were significantly lower compared to the HS, suggesting abnormal activities of brain regions in default mode network may be involved in pathophysiology of GERD symptom generation.
Although all the caregivers could not distinguish occupational therapy from physiotherapy services they all reported that therapy was important. Conclusions: A combination of psychosocial, economic, child centred and service centred factors contributed to caregivers defaulting scheduled therapy. Interventions that may ...
Schabert, A.; van Wijnbergen, S.J.G.
We analyse the impact of interactions between monetary and fiscal policy on macroeconomic stability. We find that in the presence of sovereign default beliefs a monetary policy, which aims to stabilize inflation through an active interest rate policy, will destabilize the economy if the feedback
This paper studies P2P lending and the factors explaining loan default. This is an important issue because in P2P lending individual investors bear the credit risk, instead of financial institutions, which are experts in dealing with this risk. P2P lenders suffer a severe problem of information asymmetry, because they are at a disadvantage facing the borrower. For this reason, P2P lending sites provide potential lenders with information about borrowers and their loan purpose. They also assign a grade to each loan. The empirical study is based on loans’ data collected from Lending Club (N = 24,449) from 2008 to 2014 that are first analyzed by using univariate means tests and survival analysis. Factors explaining default are loan purpose, annual income, current housing situation, credit history and indebtedness. Secondly, a logistic regression model is developed to predict defaults. The grade assigned by the P2P lending site is the most predictive factor of default, but the accuracy of the model is improved by adding other information, especially the borrower’s debt level. PMID:26425854
... the contracting office's small business specialist and the Small Business Administration Regional... default: (1) The terms of the contract and applicable laws and regulations. (2) The specific failure of... law or under the contract, in addition to charging excess costs; and (7) That the notice constitutes a...
Schabert, A.; van Wijnbergen, S.J.G.
We analyze the impact of interactions between monetary and fiscal policy on macroeconomic stability. We find that in the presence of sovereign default, macroeconomic stability requires monetary policy to be passive if the feedback from debt surprises back to the primary surplus is too weak. An
Giora, Rachel; Drucker, Ari; Fein, Ofer; Mendelson, Itamar
Findings from five experiments support the view that negation generates sarcastic utterance-interpretations by default. When presented in isolation, novel negative constructions ("Punctuality is not his forte," "Thoroughness is not her most distinctive feature"), free of semantic anomaly or internal incongruity, were…
... 47 Telecommunication 3 2010-10-01 2010-10-01 false Dispute resolution default process. 64.1703 Section 64.1703 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES... recommendation(s) must be included in the final industry-wide standard or industry-wide generic requirement...
Full Text Available The authors define a novel g-to-p prediction algorithm that utilises the concept of a 'default phoneme': a grapheme which is realised as a specific phoneme significantly more often than as any other phoneme. They found that this approach results...
Full Text Available This paper studies P2P lending and the factors explaining loan default. This is an important issue because in P2P lending individual investors bear the credit risk, instead of financial institutions, which are experts in dealing with this risk. P2P lenders suffer a severe problem of information asymmetry, because they are at a disadvantage facing the borrower. For this reason, P2P lending sites provide potential lenders with information about borrowers and their loan purpose. They also assign a grade to each loan. The empirical study is based on loans' data collected from Lending Club (N = 24,449 from 2008 to 2014 that are first analyzed by using univariate means tests and survival analysis. Factors explaining default are loan purpose, annual income, current housing situation, credit history and indebtedness. Secondly, a logistic regression model is developed to predict defaults. The grade assigned by the P2P lending site is the most predictive factor of default, but the accuracy of the model is improved by adding other information, especially the borrower's debt level.
Serrano-Cinca, Carlos; Gutiérrez-Nieto, Begoña; López-Palacios, Luz
This paper studies P2P lending and the factors explaining loan default. This is an important issue because in P2P lending individual investors bear the credit risk, instead of financial institutions, which are experts in dealing with this risk. P2P lenders suffer a severe problem of information asymmetry, because they are at a disadvantage facing the borrower. For this reason, P2P lending sites provide potential lenders with information about borrowers and their loan purpose. They also assign a grade to each loan. The empirical study is based on loans' data collected from Lending Club (N = 24,449) from 2008 to 2014 that are first analyzed by using univariate means tests and survival analysis. Factors explaining default are loan purpose, annual income, current housing situation, credit history and indebtedness. Secondly, a logistic regression model is developed to predict defaults. The grade assigned by the P2P lending site is the most predictive factor of default, but the accuracy of the model is improved by adding other information, especially the borrower's debt level.
McGuire, Megan; Munyenyembe, Tamika; Szumilin, Elisabeth; Heinzelmann, Annette; Le Paih, Mickael; Bouithy, Nenette; Pujades-Rodríguez, Mar
OBJECTIVES: To ascertain the outcome of pre-Antiretroviral therapy (ART) and ART patients defaulting from care and investigate reasons for defaulting. METHODS: Patients defaulting from HIV care in Chiradzulu between July 2004 and September 2007 were traced at last known home address. Deaths and moves were recorded, and patients found alive were interviewed. Defaulting was defined as missed last appointment by more than 1 month among patients of unknown vital status. RESULTS: A total of 1637 i...
... 42 Public Health 5 2010-10-01 2010-10-01 false Default of health education loan or scholarship... Permissive Exclusions § 1001.1501 Default of health education loan or scholarship obligations. (a... individual that the Public Health Service (PHS) determines is in default on repayments of scholarship...
... implement when developing a default prevention plan. I. Core Default Reduction Strategies 1. Establish your.... Establish a process to ensure the accuracy of your rate. II. Additional Default Reduction Strategies 1... debt management activities. 2. Enhance the enrollment retention and academic persistence of borrowers...
... 34 Education 3 2010-07-01 2010-07-01 false Preventing evasion of the consequences of cohort default rates. 668.188 Section 668.188 Education Regulations of the Offices of the Department of Education... Two Year Cohort Default Rates § 668.188 Preventing evasion of the consequences of cohort default rates...
... 34 Education 3 2010-07-01 2010-07-01 false Preventing evasion of the consequences of cohort default rates. 668.207 Section 668.207 Education Regulations of the Offices of the Department of Education... Cohort Default Rates § 668.207 Preventing evasion of the consequences of cohort default rates. (a...
Baele, L.; Farooq, M.; Ongena, S.
We compare default rates on conventional and Islamic loans using a comprehensive monthly dataset from Pakistan that follows more than 150,000 loans over the period 2006:04 to 2008:12. We find robust evidence that the default rate on Islamic loans is less than half the default rate on conventional
Webber, Karen L.; Rogers, Sharon L.
College student debt and loan default are growing concerns in the United States. For each U.S. institution, the federal government is now reporting a cohort default rate, which is the percent of students who defaulted on their loan, averaged over a three-year period. Previous studies have amply shown that student characteristics are strongly…
... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Event of Default; Application for Compensation...-STANDARD TERMS AND CONDITIONS § 230.08 Event of Default; Application for Compensation; payment. At any time after an Event of Default, as this term is defined in an Eligible Note, any Noteholder hereunder, or the...
... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Event of Default; Application for Compensation... GUARANTEE STANDARD TERMS AND CONDITIONS Procedure for Obtaining Compensation § 221.21 Event of Default; Application for Compensation; payment. At any time after an Event of Default, as this term is defined in an...
... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Event of default; Application for compensation... STANDARD TERMS AND CONDITIONS Procedure for Obtaining Compensation § 204.21 Event of default; Application for compensation; Payment. (a) Within one year after an Event of Default, as this term is defined in...
... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Event of Default; Application for Compensation... LAW 108-11-STANDARD TERMS AND CONDITIONS § 231.08 Event of Default; Application for Compensation; payment. At any time after an Event of Default, as this term is defined in an Eligible Note, any...
Rogers Baxter P
Full Text Available Abstract Background The default network is a set of brain regions that exhibit a reduction in BOLD response during attention-demanding cognitive tasks, and distinctive patterns of functional connectivity that typically include anti-correlations with a fronto-parietal network involved in attention, working memory, and executive control. The function of the default network regions has been attributed to introspection, self-awareness, and theory of mind judgments, and some of its regions are involved in episodic memory processes. Results Using the method of psycho-physiological interactions, we studied the functional connectivity of several regions in a fronto-parietal network involved in a paired image discrimination task involving transitive inference. Some image pairs were derived from an implicit underlying sequence A>B>C>D>E, and some were independent (F>G, H>J, etc. Functional connectivity between the fronto-parietal regions and the default network regions depended on the presence of the underlying sequence relating the images. When subjects viewed learned and novel pairs from the sequence, connectivity between these two networks was higher than when subjects viewed learned and novel pairs from the independent sets. Conclusions These results suggest that default network regions were involved in maintaining the internal model that subserved discrimination of image pairs derived from the implicit sequence, and contributed to introspective access of an internal sequence model built during training. The default network may not be a unified entity with a specific function, but rather may interact with other functional networks in task-dependent ways.
Full Text Available Proper credit-risk management is essential for lending institutions, as substantial losses can be incurred when borrowers default. Consequently, statistical methods that can measure and analyze credit risk objectively are becoming increasingly important. This study analyzes default payment data and compares the prediction accuracy and classification ability of three ensemble-learning methods—specifically, bagging, random forest, and boosting—with those of various neural-network methods, each of which has a different activation function. The results obtained indicate that the classification ability of boosting is superior to other machine-learning methods including neural networks. It is also found that the performance of neural-network models depends on the choice of activation function, the number of middle layers, and the inclusion of dropout.
The presence of a singleton in a task-irrelevant domain can impair visual search. This impairment, known as the attentional capture depends on the set of participants. When narrowly searching for a specific feature (the feature search mode), only matching stimuli capture attention. When searching broadly (the singleton detection mode), any oddball captures attention. The present study examined which strategy represents the "default" mode using an operant conditioning approach in which participants were trained, in the absence of explicit instructions, to search for a target in an ambiguous context in which one of two modes was available. The results revealed that participants behaviorally adopted the singleton detection as the default mode but reported using the feature search mode. Conscious strategies did not eliminate capture. These results challenge the view that a conscious set always modulates capture, suggesting that the visual system tends to rely on stimulus salience to deploy attention.
Hong Wang; Lifeng Zhou
In this paper, we propose an improved random forest algorithm which allocates weights to decision trees in the forest during tree aggregation for prediction and their weights are easily calculated based on out-of-bag errors in training. We compare the performance of our proposed algorithm and the original one on loan default prediction datasets. We also use these two algorithms to create two kinds of balanced random forests to deal with imbalanced data problem. Experiments results show that ...
Cui, J; Tymofiyeva, O; Desikan, R; Flynn, T; Kim, H; Gano, D; Hess, C P; Ferriero, D M; Barkovich, A J; Xu, D
Diffusion and fMRI has been providing insights to brain development in addition to anatomic imaging. This study aimed to evaluate the microstructure of white matter tracts underlying the default mode network in premature infants by using resting-state functional MR imaging in conjunction with diffusion tensor imaging-based tractography. A cohort of 44 preterm infants underwent structural T1-weighted imaging, resting-state fMRI, and DTI at 3T, including 21 infants with brain injuries and 23 infants with normal-appearing structural imaging as controls. Neurodevelopment was evaluated with the Bayley Scales of Infant Development at 12 months' adjusted age. Probabilistic independent component analysis was applied to resting-state fMRI data to explore resting-state networks. The localized clusters of the default mode network were used as seeding for probabilistic tractography. The DTI metrics (fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity) of the reconstructed primary tracts within the default mode network-cingula were measured. Results revealed decreased fractional anisotropy (0.20 ± 0.03) and elevated radial diffusivity values (1.24 ± 0.16) of the cingula in the preterm infants with brain injuries compared with controls (fractional anisotropy, 0.25 ± 0.03; P default mode network are of critical importance in the early neurocognitive development of infants. This study of combined resting-state fMRI and DTI at rest suggests that such studies may allow the investigation of key functional brain circuits in premature infants, which could function not only as diagnostic tools but also as biomarkers for long-term neurodevelopmental outcomes. © 2017 by American Journal of Neuroradiology.
Oka, Mizuki; Ikegami, Takashi
Social networking services (e.g., Twitter, Facebook) are now major sources of World Wide Web (called "Web") dynamics, together with Web search services (e.g., Google). These two types of Web services mutually influence each other but generate different dynamics. In this paper, we distinguish two modes of Web dynamics: the reactive mode and the default mode. It is assumed that Twitter messages (called "tweets") and Google search queries react to significant social movements and events, but they also demonstrate signs of becoming self-activated, thereby forming a baseline Web activity. We define the former as the reactive mode and the latter as the default mode of the Web. In this paper, we investigate these reactive and default modes of the Web's dynamics using transfer entropy (TE). The amount of information transferred between a time series of 1,000 frequent keywords in Twitter and the same keywords in Google queries is investigated across an 11-month time period. Study of the information flow on Google and Twitter revealed that information is generally transferred from Twitter to Google, indicating that Twitter time series have some preceding information about Google time series. We also studied the information flow among different Twitter keywords time series by taking keywords as nodes and flow directions as edges of a network. An analysis of this network revealed that frequent keywords tend to become an information source and infrequent keywords tend to become sink for other keywords. Based on these findings, we hypothesize that frequent keywords form the Web's default mode, which becomes an information source for infrequent keywords that generally form the Web's reactive mode. We also found that the Web consists of different time resolutions with respect to TE among Twitter keywords, which will be another focal point of this paper.
solution that it felt was commensurate with its deeply diminished economic and social reality. Facing a huge debt burden, Argentina adopted a hard line...34Vulture Funds Lobby Against Argentina," America Latina en Movimiento , August 6, 2009. http://alainet.org/index.phtml Argentina’s Defaulted Sovereign...Service 12 responsibility can have dramatic long-term economic, social , and political consequences. At the financial level, the costs to Argentina have
Tomasz R. Bielecki
Full Text Available The valuation and hedging of defaultable game options is studied in a hazard process model of credit risk. A convenient pricing formula with respect to a reference filteration is derived. A connection of arbitrage prices with a suitable notion of hedging is obtained. The main result shows that the arbitrage prices are the minimal superhedging prices with sigma martingale cost under a risk neutral measure.
Lanoix, J-P; Guimard, T; Ettahar, N; Grannec, A; Flateau, C; Chapuzet, C; Bentayeb, H; Tattevin, P; Schmit, J-L
Lymph node tuberculosis (LNTB) is the most frequent form of extra-pulmonary tuberculosis (TB). Randomised, controlled trials have convincingly demonstrated that 6 months of chemotherapy is sufficient for most drug-susceptible LNTB. We performed a retrospective, multicentric study from 1997 to 2010 to describe factors associated with prolonged anti-tuberculosis treatment in patients with LNTB. Of 126 patients diagnosed with LNTB, 22 (17.5%) were human immunodeficiency virus (HIV) infected. The median treatment duration was 9 months (interquartile range, 6-12). Treatment was significantly longer in patients with HIV (P < 0.01), additional sites of TB (P < 0.01) or weight loss (P = 0.04). Factors independently associated with excessively lengthy treatment were HIV co-infection and the presence of other TB foci.
Full Text Available Borrowers default risk is one of the most relevant types of risk in commercial banking and its assessment is important to secure business profitability and avoid huge losses during economic turbulences. This leads to necessity to investigate topics related to assessment of borrowers’ default probability and applicability of factors, which would enable to capture the newest trends of borrowers’ markets. Leading economic indicators (in addition to financial and other economic indicators are often suggested as forward-looking in scientific literature. However, there is still a discussion going on applicability of financial ratios and economic indicators. As the problem is relevant in theoretical view as well as for practitioners, this article aims to identify applicability of leading economic indicators for the estimation of default probability. Further, the qualitative criteria for factor selection were identified and used when using detailing, grouping and SWOT analysis methods. Based on current scientific literature analysis, this paper concludes that although leading economic indicators are able to capture forward-looking signals, they should be used with careful analysis of its drawbacks and in combination with financial factors in order to avoid overshooting effects. The limitation of the article is the analysis of factors based on rather theoretical analysis than estimation of quantitative criteria. This suggests that every time using leading economic indicators requires using empirical study of particular indicators’ set.
Messina, Irene; Bianco, Francesca; Cusinato, Maria; Calvo, Vincenzo; Sambin, Marco
Depression is widely seen as the result of difficulties in regulating emotions. Based on neuroimaging studies on voluntary emotion regulation, neurobiological models have focused on the concept of cognitive control, considering emotion regulation as a shift toward involving controlled processes associated with activation of the prefrontal and parietal executive areas, instead of responding automatically to emotional stimuli. According to such models, the weaker executive area activation observed in depressed patients is attributable to a lack of cognitive control over negative emotions. Going beyond the concept of cognitive control, psychodynamic models describe the development of individuals' capacity to regulate their emotional states in mother-infant interactions during childhood, through the construction of the representation of the self, others, and relationships. In this mini-review, we link these psychodynamic models with recent findings regarding the abnormal functioning of the default system in depression. Consistently with psychodynamic models, psychological functions associated with the default system include self-related processing, semantic processes, and implicit forms of emotion regulation. The abnormal activation of the default system observed in depression may explain the dysfunctional aspects of emotion regulation typical of the condition, such as an exaggerated negative self-focus and rumination on self-esteem issues. We also discuss the clinical implications of these findings with reference to the therapeutic relationship as a key tool for revisiting impaired or distorted representations of the self and relational objects.
Results: Seventy-four per cent of patients completed their treatment and 26% were cured, with no defaults or deaths, in the tubercuolosis/HIV integrated cohort. Thirty-eight per cent completed their treatment, 45% were cured, 9% died and another 9% defaulted in the cohort receiving their tuberculosis treatment at a local ...
Pan, H-Q; Bele, S; Feng, Y; Qiu, S-S; Lü, J-Q; Tang, S-W; Shen, H-B; Wang, J-M; Zhu, L-M
A county in Jiangsu Province, China. To estimate the costs of the diagnosis and treatment of tuberculosis (TB) from the patient's perspective and to identify determinants of the patient's financial burden. In a cross-sectional survey, we interviewed 316 patients diagnosed from January 2010 to May 2011 who had already completed their anti-tuberculosis treatment. The financial burden on TB patients included out-of-pocket costs and productivity losses. The average per capita total out-of-pocket cost was 3024.0 Chinese yuan (CNY), with a median cost of 1086 CNY (interquartile range [IQR] 480-2456). Mean out-of-pocket medical and non-medical costs were respectively 2565.7 CNY and 458.3 CNY. Productivity lost by patients and family members was 2615.2 CNY (median 500, IQR 250-2025). Factors associated with out-of-pocket costs and productivity losses included hospitalisation, adverse drug reactions, cost of drugs to 'protect' the liver, cost of second-line anti-tuberculosis drugs and diagnostic delay. Although the government of China has implemented a 'free TB service policy', the economic burden on patients is still heavy. More patient-centred interventions are essential to reduce the financial burden on patients.
Lara Anne Hale
Full Text Available Although it is often assumed that default rules affect change without awareness, this paper suggests that contrast with the default and transition into conscious adoption of the default design may be the starting point to establish long-term changes in consumer behavior. Despite the rooting of default rules in subconscious decision-making, this research finds that, ultimately, awareness drives the demand necessary for the creation of sustainable consumption. Whereas direct appeal to individuals has a disappointing level of influence on sustainability choices, it is understood that green consumers do come from somewhere. Green default rules offer interesting prospects for sidestepping the drawbacks of direct marketing to individuals. Under green default rules, behavior is guided by a default, such as utilities automatically sending customers renewables-sourced instead of fossil-fuel-based energy. To act otherwise requires additional effort and is less likely. Motivated by a need to understand how defaults might bridge standards and sustainable consumption, I investigate how organizational processes potentially lead from standardized green default rules to individual awareness that can spread and facilitate sustainable consumption. This paper examines the Active House sustainable building demonstrations in Europe in order to understand how (1 communications and market creation and (2 responsible, user-centered experimentation are organized to move from defaults to sustainable consumption.
Warren, Aaron E L; Abbott, David F; Jackson, Graeme D; Archer, John S
To identify abnormal thalamocortical circuits in the severe epilepsy of Lennox-Gastaut syndrome (LGS) that may explain the shared electroclinical phenotype and provide potential treatment targets. Twenty patients with a diagnosis of LGS (mean age = 28.5 years) and 26 healthy controls (mean age = 27.6 years) were compared using task-free functional magnetic resonance imaging (MRI). The thalamus was parcellated according to functional connectivity with 10 cortical networks derived using group-level independent component analysis. For each cortical network, we assessed between-group differences in thalamic functional connectivity strength using nonparametric permutation-based tests. Anatomical locations were identified by quantifying spatial overlap with a histologically informed thalamic MRI atlas. In both groups, posterior thalamic regions showed functional connectivity with visual, auditory, and sensorimotor networks, whereas anterior, medial, and dorsal thalamic regions were connected with networks of distributed association cortex (including the default-mode, anterior-salience, and executive-control networks). Four cortical networks (left and right executive-control network; ventral and dorsal default-mode network) showed significantly enhanced thalamic functional connectivity strength in patients relative to controls. Abnormal connectivity was maximal in mediodorsal and ventrolateral thalamic nuclei. Specific thalamocortical circuits are affected in LGS. Functional connectivity is abnormally enhanced between the mediodorsal and ventrolateral thalamus and the default-mode and executive-control networks, thalamocortical circuits that normally support diverse cognitive processes. In contrast, thalamic regions connecting with primary and sensory cortical networks appear to be less affected. Our previous neuroimaging studies show that epileptic activity in LGS is expressed via the default-mode and executive-control networks. Results of the present study suggest that
Pallesen, Karen Johanne; Brattico, Elvira; Bailey, Christopher J
cognitive load and emotional stimulus connotation on task-related decreases in the default network by employing an auditory working memory (WM) task with musical sounds. The performance of the WM task, compared to passive listening, lowered the activity in medial and lateral, prefrontal, parietal, temporal......, and limbic regions. In a subset of these regions, the magnitude of decrease depended on the memory load; the greater the cognitive load, the larger the magnitude of the observed decrease. Furthermore, in the right amygdala and the left precuneus, areas previously associated with processing of unpleasant...
Yusof, Norliza Muhamad; Anuar, Aini Hayati; Isa, Norsyaheeda Natasha; Zulkafli, Sharifah Nursyuhada Syed; Sapini, Muhamad Luqman
This paper presents a developed java android application for KMV-Merton model in predicting the defaut rate of a firm. Predicting default rate is essential in the risk management area as default risk can be immediately transmitted from one entity to another entity. This is the reason default risk is known as a global risk. Although there are several efforts, instruments and methods used to manage the risk, it is said to be insufficient. To the best of our knowledge, there has been limited innovation in developing the default risk mathematical model into a mobile application. Therefore, through this study, default risk is predicted quantitatively using the KMV-Merton model. The KMV-Merton model has been integrated in the form of java program using the Android Studio Software. The developed java android application is tested by predicting the levels of default risk of the three different rated companies. It is found that the levels of default risk are equivalent to the ratings of the respective companies. This shows that the default rate predicted by the KMV-Merton model using the developed java android application can be a significant tool to the risk mangement field. The developed java android application grants users an alternative to predict level of default risk within less procedure.
Olson, Jordan; Hollenbeak, Christopher; Donaldson, Keri; Abendroth, Thomas; Castellani, William
Computerized physician order entry (CPOE) systems are quickly becoming ubiquitous, and groups of orders ("order sets") to allow for easy order input are a common feature. This provides a streamlined mechanism to view, modify, and place groups of related orders. This often serves as an electronic equivalent of a specialty requisition. A characteristic, of these order sets is that specific orders can be predetermined to be "preselected" or "defaulted-on" whenever the order set is used while others are "optional" or "defaulted-off" (though there is typically the option is to "deselect" defaulted-on tests in a given situation). While it seems intuitive that the defaults in an order set are often accepted, additional study is required to understand the impact of these "default" settings in an order set on ordering habits. This study set out to quantify the effect of changing the default settings of an order set. For quality improvement purposes, order sets dealing with transfusions were recently reviewed and modified to improve monitoring of outcome. Initially, the order for posttransfusion hematocrits and platelet count had the default setting changed from "optional" to "preselected." The default settings for platelet count was later changed back to "optional," allowing for a natural experiment to study the effect of the default selections of an order set on clinician ordering habits. Posttransfusion hematocrit values were ordered for 8.3% of red cell transfusions when the default order set selection was "off" and for 57.4% of transfusions when the default selection was "preselected" (P default order set selection was "optional," increased to 59.4% when the default was changed to "preselected" (P default selection was returned to "optional." The posttransfusion platelet count rates during the two "optional" periods: 7.0% versus 7.5% - were not statistically different (P = 0.620). Default settings in CPOE order sets can significantly influence physician selection of
Hu, Mao-Lin; Zong, Xiao-Fen; Mann, J John; Zheng, Jun-Jie; Liao, Yan-Hui; Li, Zong-Chang; He, Ying; Chen, Xiao-Gang; Tang, Jin-Song
Schizophrenia is a severe mental disorder characterized by impaired perception, delusions, thought disorder, abnormal emotion regulation, altered motor function, and impaired drive. The default mode network (DMN), since it was first proposed in 2001, has become a central research theme in neuropsychiatric disorders, including schizophrenia. In this review, first we define the DMN and describe its functional activity, functional and anatomical connectivity, heritability, and inverse correlation with the task positive network. Second, we review empirical studies of the anatomical and functional DMN, and anti-correlation between DMN and the task positive network in schizophrenia. Finally, we review preliminary evidence about the relationship between antipsychotic medications and regulation of the DMN, review the role of DMN as a treatment biomarker for this disease, and consider the DMN effects of individualized therapies for schizophrenia.
Turner, Gary R; Spreng, R Nathan
Reduced executive control is a hallmark of neurocognitive aging. Poor modulation of lateral pFC activity in the context of increasing task challenge in old adults and a "failure to deactivate" the default network during cognitive control tasks have been observed. Whether these two patterns represent discrete mechanisms of neurocognitive aging or interact into older adulthood remains unknown. We examined whether altered pFC and default network dynamics co-occur during goal-directed planning over increasing levels of difficulty during performance on the Tower of London task. We used fMRI to investigate task- and age-related changes in brain activation and functional connectivity across four levels of task challenge. Frontoparietal executive control regions were activated and default network regions were suppressed during planning relative to counting performance in both groups. Older adults, unlike young, failed to modulate brain activity in executive control and default regions as planning demands increased. Critically, functional connectivity analyses revealed bilateral dorsolateral pFC coupling in young adults and dorsolateral pFC to default coupling in older adults with increased planning complexity. We propose a default-executive coupling hypothesis of aging. First, this hypothesis suggests that failure to modulate control and default network activity in response to increasing task challenge are linked in older adulthood. Second, functional brain changes involve greater coupling of lateral pFC and the default network as cognitive control demands increase in older adults. We speculate that these changes reflect an adaptive shift in cognitive approach as older adults come to rely more upon stored representations to support goal-directed task performance.
Brown, Chanda Denea
This study explored whether a predictive model of student loan default could be developed with data from an institution's three-year cohort default rate report. The study used borrower data provided by a large two-year community college. Independent variables under investigation included total undergraduate Stafford student loan debt, total number…
... Contributions Contract (ACC). 985.109 Section 985.109 Housing and Urban Development Regulations Relating to... § 985.109 Default under the Annual Contributions Contract (ACC). HUD may determine that an PHA's failure... required by HUD constitutes a default under the ACC. ...
... 47 Telecommunication 3 2010-10-01 2010-10-01 false Default proxies for incumbent LECs' transport... Termination of Telecommunications Traffic § 51.707 Default proxies for incumbent LECs' transport and... traffic, or for specific components included therein, that are consistent with the proxies specified in...
Gordon, Evan M.; Lee, Philip S.; Maisog, Jose M.; Foss-Feig, Jennifer; Billington, Michael E.; VanMeter, John; Vaidya, Chandan J.
A default mode network of brain regions is known to demonstrate coordinated activity during the resting state. While the default mode network is well characterized in adults, few investigations have focused upon its development. We scanned 9-13-year-old children with diffusion tensor imaging and resting-state functional magnetic resonance imaging.…
Halko, Mark A.; Eldaief, Mark C.; Horvath, Jared C.; Pascual-Leone, Alvaro
The default mode network is a group of brain regions that are active when an individual is not focused on the outside world and the brain is at "wakeful rest."1,2,3 It is thought the default mode network corresponds to self-referential or "internal mentation".2,3
... 14 Aeronautics and Space 5 2010-01-01 2010-01-01 false Analysis of costs; automation; prevention of overpayments, delinquencies, or defaults. 1261.413 Section 1261.413 Aeronautics and Space NATIONAL...) § 1261.413 Analysis of costs; automation; prevention of overpayments, delinquencies, or defaults. The...
The fuel supply report documents the data and methodology used to derive the default gasoline, diesel and fuel-blend fuel properties, and their respective fuel market share in MOVES. The default market share of the individual fuels varies by calendar year, seasons, and several do...
... 40 Protection of Environment 1 2010-07-01 2010-07-01 false Analysis of costs; automation; prevention of overpayments, delinquencies or defaults. 13.19 Section 13.19 Protection of Environment...; automation; prevention of overpayments, delinquencies or defaults. (a) The Administrator may periodically...
Nyahende, Veronica R.
The cost of students' loans defaulting has lead to a serious discussion among participants. Substantial attention has been made on the students' loans and its impact on higher education finances while researches on students' loans defaults have not been taken for more than a decade. Therefore this study examines the influence of student loans…
... Agency defaults under Agreement or Contract. The ACC, the Agreement and the Contract will provide that... enter into the Contract. (b) Rights of HUD if Agency defaults under ACC. The ACC will provide that, if...; however, HUD will continue to pay annual contributions in accordance with the terms of the ACC and the...
Spreng, R Nathan; Schacter, Daniel L
We investigated age-related changes in default, attention, and control network activity and their interactions in young and old adults. Brain activity during autobiographical and visuospatial planning was assessed using multivariate analysis and with intrinsic connectivity networks as regions of interest. In both groups, autobiographical planning engaged the default network while visuospatial planning engaged the attention network, consistent with a competition between the domains of internalized and externalized cognition. The control network was engaged for both planning tasks. In young subjects, the control network coupled with the default network during autobiographical planning and with the attention network during visuospatial planning. In old subjects, default-to-control network coupling was observed during both planning tasks, and old adults failed to deactivate the default network during visuospatial planning. This failure is not indicative of default network dysfunction per se, evidenced by default network engagement during autobiographical planning. Rather, a failure to modulate the default network in old adults is indicative of a lower degree of flexible network interactivity and reduced dynamic range of network modulation to changing task demands.
... COMMODITY FUTURES TRADING COMMISSION SECURITIES AND EXCHANGE COMMISSION [Release No. 34-63112, File No. 4-615] Joint Public Roundtable on Issues Related to the Clearing of Credit Default Swaps... certain issues related to the clearing of Credit Default Swaps in the context of the Agencies rulemaking...
Peng, Z W; Xu, T; He, Q H; Shi, C Z; Wei, Z; Miao, G D; Jing, J; Lim, K O; Zuo, X N; Chan, R C K
Aberrant functional connectivity within the default network is generally assumed to be involved in the pathophysiology of obsessive compulsive disorder (OCD); however, the genetic risk of default network connectivity in OCD remains largely unknown. Here, we systematically investigated default network connectivity in 15 OCD patients, 15 paired unaffected siblings and 28 healthy controls. We sought to examine the profiles of default network connectivity in OCD patients and their siblings, exploring the correlation between abnormal default network connectivity and genetic risk for this population. Compared with healthy controls, OCD patients exhibited reduced strength of default network functional connectivity with the posterior cingulate cortex (PCC), and increased functional connectivity in the right inferior frontal lobe, insula, superior parietal cortex and superior temporal cortex, while their unaffected first-degree siblings only showed reduced local connectivity in the PCC. These findings suggest that the disruptions of default network functional connectivity might be associated with family history of OCD. The decreased default network connectivity in both OCD patients and their unaffected siblings may serve as a potential marker of OCD.
Kleef, van Ellen; Seijdell, Karen; Vingerhoeds, Monique H.; Wijk, de René A.; Trijp, van Hans C.M.
Consumer choices are often influenced by the default option presented. This study examines the effect of whole wheat bread as a default option in a sandwich choice situation. Whole wheat bread consists of 100% whole grain and is healthier than other bread types that are commonly consumed, such as
... 10 Energy 4 2010-01-01 2010-01-01 false Default, demand, payment, and collateral liquidation. 609... PROJECTS THAT EMPLOY INNOVATIVE TECHNOLOGIES § 609.15 Default, demand, payment, and collateral liquidation... Guaranteed Obligation. Such assignment shall include all related liens, security, and collateral rights to...
... 10 Energy 4 2010-01-01 2010-01-01 false Default, demand, payment, and collateral liquidation. 611... collateral liquidation. (a) In the event that the Borrower has defaulted in the making of required payments.... Attorney General, may seek to foreclose on the collateral assets and/or take such other legal action as...
Campi, L.; Polbennikov, S.Y.; Sbuelz, A.
Unlike in structural and reduced-form models, we use equity as a liquid and observable primitive to analytically value corporate bonds and credit default swaps.Restrictive assumptions on the .rm.s capital structure are avoided.Default is parsimoniously represented by equity value hitting the zero
Full Text Available This study aims to analyze the determinants of Islamic banking credit default compared with conventional banking in Indonesia. This study utilized timeseries analysis, by which ordinary least square method is adopted. 40 monthly data observations from January 2003 until April 2006 are used. The study is divided into two models, namely Islamic banking model and conventional banking model. The values of non-performing financing (NPF in Islamic banking and non-performing loan (NPL in conventional banking are treated as the dependent variables. The results showed that two-month lagged of non-performing financing (NPF, total asset (ASSET, the amount of thirdparty-funds (TPF, one-month lagged of total financing (DFIN, and growthof gross-domestic product (GDPG variables have significant impact to the ratio of non-performing financing (NPF in Islamic banking. Meanwhile, the three-month lagged of non-performing loan (DDDNPL, total asset (CASSET, three-month as well as two-month period lagged of total loan (DDDCRED and DDCRED, inter-bank money market (PUAB, and growth of gross-domestic (GDPG are significant to influence the ratio of non-performing loan (NPL in conventional banking. The result also implied that the general election in 2004 had a significant influence to the ratio of non-performing financing (NPF in Islamic banking.Even tough from the outset, it seems Islamic banking has a better performance than conventional banking by having a relatively low NPF, this study, however, has found the opposite. Albeit, Islamic banking showing a good long-runas well as short-run dynamics among all variables in the beginning, after modifying the model into autoregressive in the main analysis, results showed that conventional banking has a better performance than Islamic banking with higher correlation of determination. In this regard, we cannot assume thatIslamic banking is performing poorly in managing credit default problems. This is because the result
Buckner, Randy L
The brain's default network is a set of regions that is spontaneously active during passive moments. The network is also active during directed tasks that require participants to remember past events or imagine upcoming events. One hypothesis is that the network facilitates construction of mental models (simulations) that can be used adaptively in many contexts. Extensive research has considered whether disruption of the default network may contribute to disease. While an intriguing possibility, a specific challenge to this notion is the fact that it is difficult to accurately measure the default network in patients where confounds of head motion and compliance are prominent. Nonetheless, some intriguing recent findings suggest that dysfunctional interactions between front-oparietal control systems and the default network contribute to psychosis. Psychosis may be a network disturbance that manifests as disordered thought partly because it disrupts the fragile balance between the default network and competing brain systems.
Li, Liang; Li, Baojuan; Bai, Yuanhan; Wang, Huaning; Zhang, Linchuan; Cui, Longbiao; Lu, Hongbing
Understanding the neural basis of Major Depressive Disorder (MDD) is important for the diagnosis and treatment of this mental disorder. The default mode network (DMN) is considered to be highly involved in the MDD. To find directed interaction between DMN regions associated with the development of MDD, the effective connectivity within the DMN of the MDD patients and matched healthy controls was estimated by using a recently developed spectral dynamic causal modeling. Sixteen patients with MDD and sixteen matched healthy control subjects were included in this study. While the control group underwent the resting state fMRI scan just once, all patients underwent resting state fMRI scans before and after two months' treatment. The spectral dynamic causal modeling was used to estimate directed connections between four DMN nodes. Statistical analysis on connection strengths indicated that efferent connections from the medial frontal cortex (MFC) to posterior cingulate cortex (PCC) and to right parietal cortex (RPC) were significant higher in pretreatment MDD patients than those of the control group. After two-month treatment, the efferent connections from the MFC decreased significantly, while those from the left parietal cortex (LPC) to MFC, PCC and RPC showed a significant increase. These findings suggest that the MFC may play an important role for inhibitory conditioning of the DMN, which was disrupted in MDD patients. It also indicates that disrupted suppressive function of the MFC could be effectively restored after two-month treatment.
Ferdinand J. Potgieter
Full Text Available Using experiential interpretivism as underpinning methodology, this article investigates whether religious fundamentalism is the default spirituality of human beings. Our research is based on a hermeneutic reconstructive interpretation of religion, fundamentalism, radicalism, extremism, spirituality, life- and worldview, and the role of education in bringing about peaceful coexistence amongst people. We concluded that the natural religious-fundamentalist inclination of the human being tends to be (and needs to be counterbalanced by the education – that is, socialisation – that he or she receives from the moment of birth, the important first six or seven years of life, and throughout his or her life. Based on this conclusion, the article ends with the articulation of ten implications for teacher education.
Full Text Available During wakefulness and in absence of performing tasks or sensory processing, the default-mode network (DMN, an intrinsic central nervous system (CNS network, is in an active state. Non-human primate and human CNS imaging studies have identified the DMN in these two species. Clinical imaging studies have shown that the pattern of activity within the DMN is often modulated in various disease states (e.g., Alzheimer's, schizophrenia or chronic pain. However, whether the DMN exists in awake rodents has not been characterized. The current data provides evidence that awake rodents also possess 'DMN-like' functional connectivity, but only subsequent to habituation to what is initially a novel magnetic resonance imaging (MRI environment as well as physical restraint. Specifically, the habituation process spanned across four separate scanning sessions (Day 2, 4, 6 and 8. At Day 8, significant (p<0.05 functional connectivity was observed amongst structures such as the anterior cingulate (seed region, retrosplenial, parietal, and hippocampal cortices. Prior to habituation (Day 2, functional connectivity was only detected (p<0.05 amongst CNS structures known to mediate anxiety (i.e., anterior cingulate (seed region, posterior hypothalamic area, amygdala and parabracial nucleus. In relating functional connectivity between cingulate-default-mode and cingulate-anxiety structures across Days 2-8, a significant inverse relationship (r = -0.65, p = 0.0004 was observed between these two functional interactions such that increased cingulate-DMN connectivity corresponded to decreased cingulate anxiety network connectivity. This investigation demonstrates that the cingulate is an important component of both the rodent DMN-like and anxiety networks.
... 34 Education 3 2010-07-01 2010-07-01 false Determining cohort default rates for institutions that have undergone a change in status. 668.184 Section 668.184 Education Regulations of the Offices of the... ASSISTANCE GENERAL PROVISIONS Two Year Cohort Default Rates § 668.184 Determining cohort default rates for...
Baele, L.; Farooq, M.; Ongena, S.
Abstract: We compare default rates on conventional and Islamic loans using a comprehensive monthly dataset from Pakistan that follows more than 150,000 loans over the period 2006:04 to 2008:12. We find robust evidence that the default rate on Islamic loans is less than half the default rate on
Sánchez-Castañeda, Cristina; de Pasquale, Francesco; Caravasso, Chiara Falletta; Marano, Massimo; Maffi, Sabrina; Migliore, Simone; Sabatini, Umberto; Squitieri, Ferdinando
To analyze brain functional connectivity in the somatomotor and default-mode networks (DMNs) of patients with Huntington disease (HD), its relationship with gray matter (GM) volume loss, and functional changes after pridopidine treatment. Ten patients and ten untreated controls underwent T1-weighted imaging and resting-state functional magnetic resonance imaging (fMRI); four patients were also assessed after 3 months of pridopidine treatment (90 mg/d). The seed-based functional connectivity patterns from the posterior cingulate cortex and the supplementary motor area (SMA), considered cortical hubs of the DMN and somatomotor networks, respectively, were computed. FMRIB Software Library voxel-based morphometry measured GM volume. Patients had GM volume decrease in all cortical and subcortical areas of the somatomotor network with preservation of the SMA, and increased somatomotor and DMN connectivity. In DMN structures, functional connectivity impairment preceded volume loss. Pridopidine reduced the intensity of these aberrant connections. The abnormal connectivity of the somatomotor and DMN observed in HD patients may represent an early dysfunction marker, as it preceded volume loss in DMN. Pridopidine reduced connectivity of these networks in all four treated patients, suggesting that connectivity is sensitive to treatment response. © 2017 John Wiley & Sons Ltd.
Kratz, Jeremy D; El-Shazly, Ahmad Y; Mambuque, Santos G; Demetria, Elpidio; Veldkamp, Peter; Anderson, Timothy S
Gynaecomastia is a common clinical presentation that varies from benign presentations in stages of human development to hormonal pathology, mainly due to hepatic dysfunction, malignancy, and adverse pharmacologic effects. We describe the development of significant bilateral gynaecomastia after starting treatment for pulmonary tuberculosis (TB) in two males with WHO stage III Human Immunodeficiency Virus (HIV) infection on stable antiretroviral regimens. Emerging reports suggest that distinct hepatic impairment in efavirenz metabolism modulates oestrogenic activity, which may be potentiated by anti-tuberculosis therapy. Clinical application includes early recognition of efavirenz-induced gynaecomastia, especially after commencing tuberculosis treatment. To avoid decreased adherence resulting from the distressing side effect of gynecomastia, transition to an alternative ART regimen over the course of tuberculosis treatment should be considered.
Ana C. Rey Deutsch
Full Text Available The paradoxical response to tuberculosis treatment consists in the appearance of new clinical or radiologic manifestations or worsening of previous injuries after an initial improvement with anti-tuberculosis therapy. It can be observed in 6 to 30 percent of the cases of tubercular meningitis. It is the consequence of an exaggerated immune reaction that should be considered since the treatment is based on the use of immunomodulators and not in the change of anti-tuberculous drugs. We present the case of an HIV negative adult with tuberculous meningitis with a good initial response to specific therapy who showed, 10 weeks later, a paradoxical reaction to treatment that responded successfully to corticosteroids
Garrison, Kathleen A; Zeffiro, Thomas A; Scheinost, Dustin; Constable, R Todd; Brewer, Judson A
Meditation has been associated with relatively reduced activity in the default mode network, a brain network implicated in self-related thinking and mind wandering. However, previous imaging studies have typically compared meditation to rest, despite other studies having reported differences in brain activation patterns between meditators and controls at rest. Moreover, rest is associated with a range of brain activation patterns across individuals that has only recently begun to be better characterized. Therefore, in this study we compared meditation to another active cognitive task, both to replicate the findings that meditation is associated with relatively reduced default mode network activity and to extend these findings by testing whether default mode activity was reduced during meditation, beyond the typical reductions observed during effortful tasks. In addition, prior studies had used small groups, whereas in the present study we tested these hypotheses in a larger group. The results indicated that meditation is associated with reduced activations in the default mode network, relative to an active task, for meditators as compared to controls. Regions of the default mode network showing a Group × Task interaction included the posterior cingulate/precuneus and anterior cingulate cortex. These findings replicate and extend prior work indicating that the suppression of default mode processing may represent a central neural process in long-term meditation, and they suggest that meditation leads to relatively reduced default mode processing beyond that observed during another active cognitive task.
Greicius, Michael D; Menon, Vinod
Deactivation refers to increased neural activity during low-demand tasks or rest compared with high-demand tasks. Several groups have reported that a particular set of brain regions, including the posterior cingulate cortex and the medial prefrontal cortex, among others, is consistently deactivated. Taken together, these typically deactivated brain regions appear to constitute a default-mode network of brain activity that predominates in the absence of a demanding external task. Examining a passive, block-design sensory task with a standard deactivation analysis (rest epochs vs. stimulus epochs), we demonstrate that the default-mode network is undetectable in one run and only partially detectable in a second run. Using independent component analysis, however, we were able to detect the full default-mode network in both runs and to demonstrate that, in the majority of subjects, it persisted across both rest and stimulus epochs, uncoupled from the task waveform, and so mostly undetectable as deactivation. We also replicate an earlier finding that the default-mode network includes the hippocampus suggesting that episodic memory is incorporated in default-mode cognitive processing. Furthermore, we show that the more a subject's default-mode activity was correlated with the rest epochs (and "deactivated" during stimulus epochs), the greater that subject's activation to the visual and auditory stimuli. We conclude that activity in the default-mode network may persist through both experimental and rest epochs if the experiment is not sufficiently challenging. Time-series analysis of default-mode activity provides a measure of the degree to which a task engages a subject and whether it is sufficient to interrupt the processes--presumably cognitive, internally generated, and involving episodic memory--mediated by the default-mode network.
Zivin, Kara; White, Jessica O; Chao, Sandra; Christensen, Anna L; Horner, Luke; Petersen, Dana M; Hobbs, Morgan R; Capreol, Grace; Halbritter, Kevin A; Jones, Christopher M
To pilot test the effectiveness, feasibility, and acceptability of instituting a 15-pill quantity default in the electronic health record for new Schedule II opioid prescriptions. A mixed-methods pilot study in two health systems, including pre-post analysis of prescribed opioid quantity and focus groups or interviews with prescribers and health system administrators. We implemented a 15-pill electronic health record default for new Schedule II opioids and assessed opioid quantity before and after implementation using electronic health record data on 6,390 opioid prescriptions from 448 prescribers. We then analyzed themes from focus groups and interviews with four staff members and six prescribers. The proportion of opioid prescriptions for 15 pills increased at both sites after adding an electronic health record default, with one reaching statistical significance (from 4.1% to 7.2% at CHC, P = 0.280, and 15.9% to 37.2% at WVU, P default, although ease of implementation varied by electronic health record vendor. Most prescribers were not aware of the default change and stated that they made prescribing decisions based on patient clinical characteristics rather than defaults. This pilot provides initial evidence that changing default settings can increase the number of prescriptions at the default level. This low-cost and relatively simple intervention could have an impact on opioid overprescribing. However, default settings should be selected carefully to avoid unintended consequences. © 2018 American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: firstname.lastname@example.org
van Kleef, Ellen; Seijdell, Karen; Vingerhoeds, Monique H; de Wijk, René A; van Trijp, Hans C M
Consumer choices are often influenced by the default option presented. This study examines the effect of whole wheat bread as a default option in a sandwich choice situation. Whole wheat bread consists of 100% whole grain and is healthier than other bread types that are commonly consumed, such as brown or white bread. A pilot survey (N = 291) examined the strength of combinations of toppings and bread type as carrier to select stimuli for the main study. In the main experimental study consisting of a two (bread type) by two (topping type) between-subjects design, participants (N = 226) were given a free sandwich at a university stand with either a relatively unhealthy deep-fried snack (croquette) or a healthy topping. About half of the participants were offered a whole wheat bun unless they asked for white bun, and the other half were offered a white bun unless they asked for a whole wheat bun. Regardless of the topping, the results show that when the whole wheat bun was the default option, 108 out of 115 participants (94%) decided to stick with this default option. When the default of bread offered was white, 89 out of 111 participants (80%) similarly chose to stick with this default. Across conditions, participants felt equally free to make a choice. The attractiveness of and willingness to pay for the sandwich were not affected by default type of bread. This study demonstrated a strong default effect of bread type. This clearly shows the benefit of steering consumers towards a healthier bread choice, by offering healthier default bread at various locations such as restaurants, schools and work place canteens. Copyright © 2017 Elsevier Ltd. All rights reserved.
Full Text Available This paper studies the pricing of intensity-based defaultable bonds where the volatility of default intensity is assumed to be random and driven by two different factors varying on fast and slow time scales. Corrections to the constant intensity of default are obtained and then how these corrections influence the term structure of interest rate derivatives is shown. The results indicate that the fast scale correction produces a more significant impact on the bond price than the slow scale correction and the impact tends to increase as time to maturity increases.
In June of 2003, Bechtel Jacobs Company LLC tasked Pacific Western Technologies (PWT) to perform a comprehensive audit of the Facility Acceptance Testing/ Container Analysis Tool (FAT-CAT), which is currently administered, by Bechtel Jacobs Company LLC... During this audit, a finding was issued on the subject of assigning historic Y-12 default radiological activity values to radiological containers, having no radiological data. Analysis of default radiological values versus known real radiological values showed the default values to be conservative as a place-holder for containers with no known radiological values. (authors)
Höglund, Lena; Räisänen, Jouni; Hämäläinen, Anne-Maija
Default values are often used in exposure assessments e.g. in modelling because of lack of actually measured data. The quality of the exposure assessment outcome is therefore heavily dependent on the validity and representativeness this input data. Today the used default factors consist of a wide...... and dust ingestion, drinking water, food intake, non-dietary ingestion factors, lifetime expectancy, activity factors and consumer products......) and children in relation to REACH. Another important purpose of the report is to contribute towards a further harmonisation of exposure factors by giving recommendations of most valid and representative defaults. These recommendations can be used besides REACH also in biocide's and plant protection product...
Dharmaraja, Selvamuthu; Pasricha, Puneet; Tardelli, Paola
This article deals with the problem of probabilistic prediction of the time distance to default for a firm. To model the credit risk, the dynamics of an asset is described as a function of a homogeneous discrete time Markov chain subject to a catastrophe, the default. The behaviour of the Markov chain is investigated and the mean time to the default is expressed in a closed form. The methodology to estimate the parameters is given. Numerical results are provided to illustrate the applicability of the proposed model on real data and their analysis is discussed.
Clemm von Hohenberg, Christian; Weber-Fahr, Wolfgang; Lebhardt, Philipp; Ravi, Namasivayam; Braun, Urs; Gass, Natalia; Becker, Robert; Sack, Markus; Cosa Linan, Alejandro; Gerchen, Martin Fungisai; Reinwald, Jonathan Rochus; Oettl, Lars-Lennart; Meyer-Lindenberg, Andreas; Vollmayr, Barbara; Kelsch, Wolfgang; Sartorius, Alexander
Hyperconnectivity of the default-mode network (DMN) is one of the most widely replicated neuroimaging findings in major depressive disorder (MDD). Further, there is growing evidence for a central role of the lateral habenula (LHb) in the pathophysiology of MDD. There is preliminary neuroimaging evidence linking LHb and the DMN, but no causal relationship has been shown to date. We combined optogenetics and functional magnetic resonance imaging (fMRI), to establish a causal relationship, using an animal model of treatment-resistant depression, namely Negative Cognitive State rats. First, an inhibitory light-sensitive ion channel was introduced into the LHb by viral transduction. Subsequently, laser stimulation was performed during fMRI acquisition on a 9.4 Tesla animal scanner. Neural activity and connectivity were assessed, before, during and after laser stimulation. We observed a connectivity decrease in the DMN following laser-induced LHb perturbation. Our data indicate a causal link between LHb downregulation and reduction in DMN connectivity. These findings may advance our mechanistic understanding of LHb inhibition, which had previously been identified as a promising therapeutic principle, especially for treatment-resistant depression.
Xue, Jing; Yao, Yimin; Liu, Limin
Tuberculous aortic pseudoaneurysm associated with vertebral tuberculosis is a rare disease but with very high mortality. We review the literature and find 19 reports with 22 patients. Here we report three cases with vertebral tuberculosis, who also have tuberculous pseudoaneurysm of the aorta. These patients were treated by different methods. We try to analyze the epidemiology, pathogenesis, presentation, and management of this disease to find the best treatment. The patients presented with different symptoms such as pain (chest, abdominal or back), fever, blood volume reduction or hemorrhagic shock symptoms. Large mass also could be observed by imaging. In addition to clinical manifestations, enhanced computed tomography or magnetic resonance imaging could also help the diagnosis of this disease. Tuberculous aortic pseudoaneurysm associated with vertebral tuberculosis. Three patients were treated with anti-tuberculosis(TB) drugs or combined with different sequences surgical treatment: Case 1 refused to receive pseudoaneurysm surgery and only had anti-TB drug treatment; Case 2 received thoracic spinal surgery first; Case 3 received endovascular stent grafting. Two patients (case 1 and case 2) who refused to undergo aneurysm surgery died. The last patient (case 3) underwent endovascular repair and antibiotic therapy for tuberculosis, and the postoperative course was uneventful; the patient recovered and survived. Once the diagnosis of tuberculous pseudoaneurysm is confirmed, surgical treatment should be provided immediately combined with anti-tuberculosis drugs. The aim of the treatment is to save lives, prevent relapse, and facilitate the return to normal life, regardless of the size of the pseudoaneurysm. The pseudoaneurysm should be treated first to prevent aneurysm rupture before the vertebral tuberculosis surgery.
Broulidakis, M John; Fairchild, Graeme; Sully, Kate; Blumensath, Thomas; Darekar, Angela; Sonuga-Barke, Edmund J S
Conduct disorder (CD) is characterized by impulsive, aggressive, and antisocial behaviors that might be related to deficits in empathy and moral reasoning. The brain's default mode network (DMN) has been implicated in self-referential cognitive processes of this kind. This study examined connectivity between key nodes of the DMN in 29 adolescent boys with CD and 29 age- and sex-matched typically developing adolescent boys. The authors ensured that group differences in DMN connectivity were not explained by comorbidity with other disorders by systematically controlling for the effects of substance use disorders (SUDs), attention-deficit/hyperactivity disorder (ADHD) symptoms, psychopathic traits, and other common mental health problems. Only after adjusting for co-occurring ADHD symptoms, the group with CD showed hypoconnectivity between core DMN regions compared with typically developing controls. ADHD symptoms were associated with DMN hyperconnectivity. There was no effect of psychopathic traits on DMN connectivity in the group with CD, and the key results were unchanged when controlling for SUDs and other common mental health problems. Future research should directly investigate the possibility that the aberrant DMN connectivity observed in the present study contributes to CD-related deficits in empathy and moral reasoning and examine self-referential cognitive processes in CD more generally. Copyright © 2016 American Academy of Child and Adolescent Psychiatry. All rights reserved.
Thatcher, Robert W; North, Duane M; Biver, Carl J
The purpose of this study was to explore phase reset of 3-dimensional current sources in Brodmann areas located in the human default mode network (DMN) using Low Resolution Electromagnetic Tomography (LORETA) of the human electroencephalogram (EEG). The EEG was recorded from 19 scalp locations from 70 healthy normal subjects ranging in age from 13 to 20 years. A time point by time point computation of LORETA current sources were computed for 14 Brodmann areas comprising the DMN in the delta frequency band. The Hilbert transform of the LORETA time series was used to compute the instantaneous phase differences between all pairs of Brodmann areas. Phase shift and lock durations were calculated based on the 1st and 2nd derivatives of the time series of phase differences. Phase shift duration exhibited three discrete modes at approximately: (1) 25 ms, (2) 50 ms, and (3) 65 ms. Phase lock duration present primarily at: (1) 300-350 ms and (2) 350-450 ms. Phase shift and lock durations were inversely related and exhibited an exponential change with distance between Brodmann areas. The results are explained by local neural packing density of network hubs and an exponential decrease in connections with distance from a hub. The results are consistent with a discrete temporal model of brain function where anatomical hubs behave like a "shutter" that opens and closes at specific durations as nodes of a network giving rise to temporarily phase locked clusters of neurons for specific durations.
Howard-Jones, Paul A; Jay, Tim; Mason, Alice; Jones, Harvey
We hypothesized that embedding educational learning in a game would improve learning outcomes, with increased engagement and recruitment of cognitive resources evidenced by increased activation of working memory network (WMN) and deactivation of default mode network (DMN) regions. In an fMRI study, we compared activity during periods of learning in three conditions that were increasingly game-like: Study-only (when periods of learning were followed by an exemplar question together with its correct answer), Self-quizzing (when periods of learning were followed by a multiple choice question in return for a fixed number of points) and Game-based (when, following each period of learning, participants competed with a peer to answer the question for escalating, uncertain rewards). DMN hubs deactivated as conditions became more game-like, alongside greater self-reported engagement and, in the Game-based condition, higher learning scores. These changes did not occur with any detectable increase in WMN activity. Additionally, ventral striatal activation was associated with responding to questions and receiving positive question feedback. Results support the significance of DMN deactivation for educational learning, and are aligned with recent evidence suggesting DMN and WMN activity may not always be anti-correlated.
Crump, Kenny S
In an article recently published in this journal, Bogen (1) concluded that an NRC committee's recommendations that default linear, nonthreshold (LNT) assumptions be applied to dose- response assessment for noncarcinogens and nonlinear mode of action carcinogens are not justified. Bogen criticized two arguments used by the committee for LNT: when any new dose adds to a background dose that explains background levels of risk (additivity to background or AB), or when there is substantial interindividual heterogeneity in susceptibility (SIH) in the exposed human population. Bogen showed by examples that SIH can be false. Herein is outlined a general proof that confirms Bogen's claim. However, it is also noted that SIH leads to a nonthreshold population distribution even if individual distributions all have thresholds, and that small changes to SIH assumptions can result in LNT. Bogen criticizes AB because it only applies when there is additivity to background, but offers no help in deciding when or how often AB holds. Bogen does not contradict the fact that AB can lead to LNT but notes that, even if low-dose linearity results, the response at higher doses may not be useful in predicting the amount of low-dose linearity. Although this is theoretically true, it seems reasonable to assume that generally there is some quantitative relationship between the low-dose slope and the slope suggested at higher doses. Several incorrect or misleading statements by Bogen are noted. © 2016 Society for Risk Analysis.
Mohammad Khodaei Valahzaghard
Full Text Available This study examines the relationship between CAMELS index and default probability among 20 Iranian banks. The proposed study gathers the necessary information from their financial statements over the period 2005-2011. The study uses logistic regression along with Pearson correlation analysis to consider the relationship between default probability and six independent variables including capital adequacy, asset quality, management quality, earning quality, liquidity quality and sensitivity of market risk. The results indicate that there were no meaningful relationship between default probability and three independent variables including capital adequacy, asset quality and sensitivity of market risk. However, the results of our statistical tests support such relationship between default probability and three other variables including management quality, earning quality and liquidity quality.
Full Text Available Arguably a cornerstone of credit risk modelling is the probability of default. This article aims is to search for the evidence of relationship between loan characteristics and probability of default on peer-to-peer (P2P market. In line with that, two loan characteristics are analysed: 1 loan term length and 2 loan purpose. The analysis is conducted using survival analysis approach within the vintage framework. Firstly, 12 months probability of default through the cycle is used to compare riskiness of analysed loan characteristics. Secondly, log-rank test is employed in order to compare complete survival period of cohorts. Findings of the paper suggest that there is clear evidence of relationship between analysed loan characteristics and probability of default. Longer term loans are more risky than the shorter term ones and the least risky loans are those used for credit card payoff.
Peeters, Sanne C. T.; van de Ven, Vincent; Gronenschild, Ed H. B. M.; Patel, Ameera X.; Habets, Petra; Goebel, Rainer; van Os, Jim; Marcelis, Machteld; Kahn, Rene; Linszen, Don; Wiersma, Durk; Bruggeman, Richard; Cahn, Wiepke; de Haan, Lieuwe; Krabbendam, Lydia; Myin-Germeys, Inez
Background Research suggests that altered interregional connectivity in specific networks, such as the default mode network (DMN), is associated with cognitive and psychotic symptoms in schizophrenia. In addition, frontal and limbic connectivity alterations have been associated with trauma, drug use
Andrews-Hanna, Jessica R.; Smallwood, Jonathan; Spreng, R. Nathan
Though only a decade has elapsed since the default network was first emphasized as being a large-scale brain system, recent years have brought great insight into the network’s adaptive functions. A growing theme highlights the default network as playing a key role in internally-directed—or self-generated—thought. Here, we synthesize recent findings from cognitive science, neuroscience, and clinical psychology to focus attention on two emerging topics as current and future directions surrounding the default network. First, we present evidence that self-generated thought is a multi-faceted construct whose component processes are supported by different subsystems within the network. Second, we highlight the dynamic nature of the default network, emphasizing its interaction with executive control systems when regulating aspects of internal thought. We conclude by discussing clinical implications of disruptions to the integrity of the network, and consider disorders when thought content becomes polarized or network interactions become disrupted or imbalanced. PMID:24502540
Stracke, Christian M.
Stracke, C. M. (2016, 14 April). How to re-establish Openness as default? Towards a global joint initiative. Results from the Action Lab at the Open Education Global Conference 2016, Krakow, Poland. More about the Action Lab:
Jenum, Synne; Bakken, Rasmus; Dhanasekaran, S
Biomarkers reflecting the extent of Mycobacterium tuberculosis-induced pathology and normalization during anti-tuberculosis treatment (ATT) would considerably facilitate trials of new treatment regimens and the identification of patients with treatment failure. Therefore, in a cohort of 99 Indian...... children with intrathoracic tuberculosis (TB), we performed blood transcriptome kinetic analysis during ATT to explore 1) the association between transcriptional biomarkers in whole blood (WB) and the extent of TB disease at diagnosis and treatment outcomes at 2 and 6 months, and 2) the potential...... of the biomarkers to predict treatment response at 2 and 6 months. We present the first data on the association between transcriptional biomarkers and the extent of TB disease as well as outcome of ATT in children: Expression of three genes down-regulated on ATT (FCGR1A, FPR1 and MMP9) exhibited a positive...
Pesaran, Hashem; Xu, TengTeng
This paper proposes a theoretical framework to analyze the impacts of credit and technology shocks on business cycle dynamics, where firms rely on banks and households for capital financing. Firms are identical ex ante but differ ex post due to different realizations of firm specific technology shocks, possibly leading to default by some firms. The paper advances a new modelling approach for the analysis of financial intermediation and firm defaults that takes account of the financial implica...
Jiao, Zhuqing; Wang, Huan; Ma, Kai; Zou, Ling; Xiang, Jianbo
Nowadays, there is a lot of interest in assessing functional interactions between key brain regions. In this paper, Granger causality analysis (GCA) and motif structure are adopted to study directed connectivity of brain default mode networks (DMNs) in resting state. Firstly, the time series of functional magnetic resonance imaging (fMRI) data in resting state were extracted, and the causal relationship values of the nodes representing related brain regions are analyzed in time domain to construct a default network. Then, the network structures were searched from the default networks of controls and patients to determine the fixed connection mode in the networks. The important degree of motif structures in directed connectivity of default networks was judged according to p-value and Z-score. Both node degree and average distance were used to analyze the effect degree an information transfer rate of brain regions in motifs and default networks, and efficiency of the network. Finally, activity and functional connectivity strength of the default brain regions are researched according to the change of energy distributions between the normals and the patients' brain regions. Experimental results demonstrate that, both normal subjects and stroke patients have some corresponding fixed connection mode of three nodes, and the efficiency and power spectrum of the patient's default network is somewhat lower than that of the normal person. In particular, the Right Posterior Cingulate Gyrus (PCG.R) has a larger change in functional connectivity and its activity. The research results verify the feasibility of the application of GCA and motif structure to study the functional connectivity of default networks in resting state.
Mohammed Farik; ABM Shawkat Ali
Abstract Password authentication is the main means of access control on network routers and router manufacturers provide a default password for initial login to the router. While there has been many publications regarding the minimum requirements of a good password how widely the manufacturers themselves are adhering to the minimum standards and whether these passwords can withstand brute-force attack are not widely known. The novelty of this research is that this is the first time default...
What are the determinants and economic consequences of cross-border asset positions? I develop a new quantitative portfolio choice model and apply it to emerging market international finance. The model allows for partial default and accommodates trade in a rich set of assets. The latter means I am able to draw distinctions both between debt and equity finance and between gross and net debt. The main contribution is in developing portfolio choice techniques to analyze capital flows and default...
Loeb, Katharine L; Radnitz, Cynthia; Keller, Kathleen; Schwartz, Marlene B; Marcus, Sue; Pierson, Richard N; Shannon, Michael; DeLaurentis, Danielle
Optimal defaults is a compelling model from behavioral economics and the psychology of human decision-making, designed to shape or "nudge" choices in a positive direction without fundamentally restricting options. The current study aimed to test the effectiveness of optimal (less obesogenic) defaults and parent empowerment priming on health-based decisions with parent-child (ages 3-8) dyads in a community-based setting. Two proof-of-concept experiments (one on breakfast food selections and one on activity choice) were conducted comparing the main and interactive effects of optimal versus suboptimal defaults, and parent empowerment priming versus neutral priming, on parents' health-related choices for their children. We hypothesized that in each experiment, making the default option more optimal will lead to more frequent health-oriented choices, and that priming parents to be the ultimate decision-makers on behalf of their child's health will potentiate this effect. Results show that in both studies, default condition, but not priming condition or the interaction between default and priming, significantly predicted choice (healthier vs. less healthy option). There was also a significant main effect for default condition (and no effect for priming condition or the interaction term) on the quantity of healthier food children consumed in the breakfast experiment. These pilot studies demonstrate that optimal defaults can be practicably implemented to improve parents' food and activity choices for young children. Results can inform policies and practices pertaining to obesogenic environmental factors in school, restaurant, and home environments. Copyright © 2017 Elsevier Ltd. All rights reserved.
Full Text Available OBJECTIVES: Fixed-dose combination formulations, which simplify the administration of drugs and prevent the development of drug resistance, have been recommended as a standard anti-tuberculosis treatment regimen. However, the composition and dosage recommendations for fixed-dose combination formulations differ from those for separate formulations. Thus, questions about the effectiveness and side effects of combination formulations remain. The aim of this study was to compare the safety and efficacy of these two types of anti-tuberculosis regimens for pulmonary tuberculosis treatment. METHOD: A prospective, randomized controlled study was conducted using the directly observed treatment short-course strategy. Patients were randomly allocated to one of two short-course regimens. One year after completing the treatment, these patients’ outcomes were analyzed. ClinicalTrials.gov: NCT00979290. RESULTS: A total of 161 patients were enrolled, 142 of whom were evaluable for safety assessment. The two regimens had a similar incidence of adverse effects. In the per-protocol population, serum bilirubin concentrations at the peak level, at week 4, and at week 8 were significantly higher for the fixed-dose combination formulation than for the separate formulations. All patients had negative sputum cultures at the end of the treatment, and no relapse occurred after one year of follow-up. CONCLUSIONS: In this randomized study, transient higher serum bilirubin levels were noted for the fixed-dose combination regimen compared with the separate formulations during treatment. However, no significant difference in safety or efficacy was found between the groups when the directly observed treatment short-course strategy was used.
Pinto, Carlos; Machado, Armando
To investigate the coding strategies that pigeons may use in a temporal discrimination tasks, pigeons were trained on a matching-to-sample procedure with three sample durations (2s, 6s and 18s) and two comparisons (red and green hues). One comparison was correct following 2-s samples and the other was correct following both 6-s and 18-s samples. Tests were then run to contrast the predictions of two hypotheses concerning the pigeons' coding strategies, the multiple-coding and the single-code/default. According to the multiple-coding hypothesis, three response rules are acquired, one for each sample. According to the single-code/default hypothesis, only two response rules are acquired, one for the 2-s sample and a "default" rule for any other duration. In retention interval tests, pigeons preferred the "default" key, a result predicted by the single-code/default hypothesis. In no-sample tests, pigeons preferred the key associated with the 2-s sample, a result predicted by multiple-coding. Finally, in generalization tests, when the sample duration equaled 3.5s, the geometric mean of 2s and 6s, pigeons preferred the key associated with the 6-s and 18-s samples, a result predicted by the single-code/default hypothesis. The pattern of results suggests the need for models that take into account multiple sources of stimulus control. © Society for the Experimental Analysis of Behavior.
This review is prepared to show results on the anti-TB activity of -lactam antibiotics. -Lactams are among the oldest drugs with little or no side effects. Both in vitro studies and clinical data indicate that -lactams have a promising activity for use in the management of MDR-TB. More studies are required to define the interaction ...
Summary: Tuberculosis (TB) is of great public health burden globally especially in developing countries of Africa and. Asia . Current TB regimen involves multiple therapies and of long duration leading to poor patient adherence. There is also the challenge of multidrug resistant TB. Hence, there is a need for discovery of ...
Summary: Tuberculosis (TB) is of great public health burden globally especially in developing countries of Africa and Asia . Current TB regimen involves multiple therapies and of long duration leading to poor patient adherence. There is also the challenge of multidrug resistant TB. Hence, there is a need for discovery of new ...
Background: Tuberculosis remains a disease of serious socio-economic and public health importance. The morbidity and mortality burden of tuberculosis in. Nigeria and globally is great. Method: This is a non-randomized hospital based intervention study. Aim: To evaluate the impact of intensive patient education on ...
Laura Inés Plata-Casas
Full Text Available Objetivo: describir los factores de riesgo asociados a la no adherencia al tratamiento en los pacientes adscritos al programa de tuberculosis en el Municipio de Villavicencio, cohorte 2012. Materiales y Métodos: se ha realizado un estudio descriptivo de corte transversal con enfoque cuantitativo. Se obtuvieron datos de caracterización sociodemográfica sobre factores de riesgo de personas que abandonaron el tratamiento para la enfermedad- cohorte 2012- mediante la aplicación de un instrumento diseñado por el investigador y revisado por expertos. Los datos fueron tabulados y analizados mediante la herramienta Microsoft Excel® 2007 y Epi-info 7.0. Resultados: el 75% de los pacientes pertenecen al género masculino; el promedio de edad es de 30 años, el 63% pertenecen al régimen subsidiado de salud. Las principales causas de abandono fueron: efectos adversos a los medicamentos (58%, inadecuada atención del personal de salud (43%, dificultad de acceso al servicio (32%. Los factores sociales encontrados fueron hacinamiento 67% y desempleo 62%. Conclusiones: algunos factores no modificables como la edad y el género, así como factores modificables como estilos de vida inadecuados y efectos adversos; cuyo control mejoraría el cumplimiento; contribuyen al abandono del tratamiento. Las variables psicológicas y sociales deben ser evaluadas para que se conviertan en predictores de probables abandonos o irregularidades en el tratamiento antituberculoso.
Liu, Peng; Qin, Wei; Tian, Jie; Zhang, Yi
According to Traditional Chinese Medicine (TCM) theory and certain clinical treatment reports, the sustained effects of acupuncture indeed exist, which may last several minutes or hours. Furthermore, increased attention has fallen on the sustained effects of acupuncture. Recently, it is reported that the sustained acupuncture effects may alter the default mode network (DMN). It raises interesting questions: whether the modulations of acupuncture effects to the DMN are still detected at other acupoints and whether the modulation patterns are different induced by different acupoints. In the present study, we wanted to investigate the questions. An experiment fMRI design was carried out on 36 subjects with the electroacupuncture stimulation (EAS) at the three acupoints: Guangming (GB37), Kunlun (BL60) and Jiaoxin (KI8) on the left leg. The data sets were analyzed by a data driven method named independent component analysis (ICA). The results indicated that the three acupoints stimulations may modulate the DMN. Moreover, the modulation patterns were distinct. We suggest the different modulation patterns on the DMN may attribute to the distinct functional effects of acupoints.
Jing, Wei; Guo, Daqing; Zhang, Yunxiang; Guo, Fengru; Valdés-Sosa, Pedro A; Xia, Yang; Yao, Dezhong
Functional MRI (fMRI) studies have demonstrated that the rodent brain shows a default mode network (DMN) activity similar to that in humans, offering a potential preclinical model both for physiological and pathophysiological studies. However, the neuronal mechanism underlying rodent DMN remains poorly understood. Here, we used electrophysiological data to analyze the power spectrum and estimate the directed phase transfer entropy (dPTE) within rat DMN across three vigilance states: wakeful rest (WR), slow-wave sleep (SWS), and rapid-eye-movement sleep (REMS). We observed decreased gamma powers during SWS compared with WR in most of the DMN regions. Increased gamma powers were found in prelimbic cortex, cingulate cortex, and hippocampus during REMS compared with WR, whereas retrosplenial cortex showed a reverse trend. These changed gamma powers are in line with the local metabolic variation of homologous brain regions in humans. In the analysis of directional interactions, we observed well-organized anterior-to-posterior patterns of information flow in the delta band, while opposite patterns of posterior-to-anterior flow were found in the theta band. These frequency-specific opposite patterns were only observed in WR and REMS. Additionally, most of the information senders in the delta band were also the receivers in the theta band, and vice versa. Our results provide electrophysiological evidence that rat DMN is similar to its human counterpart, and there is a frequency-dependent reentry loop of anterior-posterior information flow within rat DMN, which may offer a mechanism for functional integration, supporting conscious awareness.
Robert W. Thatcher
Full Text Available Objectives: The purpose of this study was to explore phase reset of 3-dimensional current sources located in Brodmann areas located in the human default mode network (DMN using Low Resolution Electromagnetic Tomography (LORETA of the human electroencephalogram (EEG. Methods: The EEG was recorded from 19 scalp locations from 70 healthy normal subjects ranging in age from 13 to 20 years. A time point by time point computation of LORETA current sources were computed for 14 Brodman areas comprising the DMN in the delta frequency band. The Hilbert transform of the LORETA time series was used to compute the instantaneous phase differences between all pairs of Brodmann areas. Phase shift and lock durations were calculated based on the 1st & 2nd derivatives of the time series of phase differences. Results: Phase shift duration exhibited three discrete modes at approximately: 1- 30 msec,, 2- 55 msec and, 3- 65 msec. Phase lock duration present primarily at: 1- 300 to 350 msec and, 2- 350 msec to 450 msec. Phase shift and lock durations were inversely related and exhibited an exponential change with distance between Brodmann areas. Conclusions: The results are explained by local neural packing density of network hubs and an exponential decrease in connections with distance from a hub. The results are consistent with a discrete temporal model of brain function where anatomical hubs behave like a ‘shutter’ that opens and closes at specific durations as nodes of a network giving rise to temporarily phase locked clusters of neurons for specific durations.
Jaquette, Ozan; Hillman, Nicholas W.
Both federal spending on financial aid and student loan default rates have increased over the past decade. These trends have intensified policymakers' concerns that some postsecondary institutions-- particularly in the for-profit sector--maximize revenue derived from federal financial aid without helping students to graduate or find employment.…
Dornic, N; Ficheux, A S; Bernard, A; Roudot, A C
The notes of guidance for the testing of cosmetic ingredients and their safety evaluation by the Scientific Committee on Consumer Safety (SCCS) is a document dedicated to ensuring the safety of European consumers. This contains useful data for risk assessment such as default values for Skin Surface Area (SSA). A more in-depth study of anthropometric data across Europe reveals considerable variations. The default SSA value was derived from a study on the Dutch population, which is known to be one of the tallest nations in the World. This value could be inadequate for shorter populations of Europe. Data were collected in a survey on cosmetic consumption in France. Probabilistic treatment of these data and analysis of the case of methylisothiazolinone, a sensitizer recently evaluated by a deterministic approach submitted to SCCS, suggest that the default value for SSA used in the quantitative risk assessment might not be relevant for a significant share of the French female population. Others female populations of Southern Europe may also be excluded. This is of importance given that some studies show an increasing risk of developping skin sensitization among women. The disparities in anthropometric data across Europe should be taken into consideration. Copyright © 2017 Elsevier Ltd. All rights reserved.
Cui, Ying; Jiao, Yun; Chen, Hua-Jun; Ding, Jie; Luo, Bing; Peng, Cheng-Yu; Ju, Sheng-Hong; Teng, Gao-Jun
Type 2 diabetes mellitus is associated with increased risk for dementia. Patients with impaired cognition often show default-mode network disruption. We aimed to investigate the integrity of a default-mode network in diabetic patients by using independent component analysis, and to explore the relationship between network abnormalities, neurocognitive performance and diabetic variables. Forty-two patients with type 2 diabetes and 42 well-matched healthy controls were included and underwent resting-state functional MRI in a 3 Tesla unit. Independent component analysis was adopted to extract the default-mode network, including its anterior and posterior components. Z-maps of both sub-networks were compared between the two groups and correlated with each clinical variable. Patients showed increased connectivity around the medial prefrontal cortex in the anterior sub-network, but decreased connectivity around the posterior cingulate cortex in the posterior sub-network. The decreased connectivity in the posterior part was significantly correlated with the score on Complex Figure Test-delay recall test (r = 0.359, p = 0.020), the time spent on Trail-Making Test-part B (r = -0.346, p = 0.025) and the insulin resistance level (r = -0.404, p = 0.024). Dissociation pattern in the default-mode network was found in diabetic patients, which might provide powerful new insights into the neural mechanisms that underlie the diabetes-related cognitive decline. • Type 2 diabetes mellitus is associated with impaired cognition • Default- mode network plays a central role in maintaining normal cognition • Network connectivity within the default mode was disrupted in type 2 diabetes patients • Decreased network connectivity was correlated with cognitive performance and insulin resistance level • Disrupted default-mode network might explain the impaired cognition in diabetic population.
It remains unclear whether and to what extent the default network subregions involved in episodic memory (EM) and semantic memory (SM) processes overlap or are separated from one another. This study addresses this issue through a controlled meta-analysis of functional neuroimaging studies involving healthy participants. Various EM and SM task paradigms differ widely in the extent of default network involvement. Therefore, the issue at hand cannot be properly addressed without some control for this factor. In this regard, this study employs a two-stage analysis: a preliminary meta-analysis to select EM and SM task paradigms that recruit relatively extensive default network regions and a main analysis to compare the selected task paradigms. Based on a within-EM comparison, the default network contributed more to recollection/familiarity effects than to old/new effects, and based on a within-SM comparison, it contributed more to word/pseudoword effects than to semantic/phonological effects. According to a direct comparison of recollection/familiarity and word/pseudoword effects, each involving a range of default network regions, there were more overlaps than separations in default network subregions involved in these two effects. More specifically, overlaps included the bilateral posterior cingulate/retrosplenial cortex, left inferior parietal lobule, and left anteromedial prefrontal regions, whereas separations included only the hippocampal formation and the parahippocampal cortex region, which was unique to recollection/familiarity effects. These results indicate that EM and SM retrieval processes involving strong memory signals recruit extensive and largely overlapping default network regions and differ mainly in distinct contributions of hippocampus and parahippocampal regions to EM retrieval. Copyright © 2015 Elsevier Ltd. All rights reserved.
Karunanayaka, Prasanna R; Wilson, Donald A; Tobia, Michael J; Martinez, Brittany E; Meadowcroft, Mark D; Eslinger, Paul J; Yang, Qing X
Default mode network (DMN) deactivation has been shown to be functionally relevant for goal-directed cognition. In this study, the DMN's role during olfactory processing was investigated using two complementary functional magnetic resonance imaging (fMRI) paradigms with identical timing, visual-cue stimulation, and response monitoring protocols. Twenty-nine healthy, non-smoking, right-handed adults (mean age = 26 ± 4 years, 16 females) completed an odor-visual association fMRI paradigm that had two alternating odor + visual and visual-only trial conditions. During odor + visual trials, a visual cue was presented simultaneously with an odor, while during visual-only trial conditions the same visual cue was presented alone. Eighteen of the twenty-nine participants (mean age = 27.0 ± 6.0 years, 11 females) also took part in a control no-odor fMRI paradigm that consisted of a visual-only trial condition which was identical to the visual-only trials in the odor-visual association paradigm. Independent Component Analysis (ICA), extended unified structural equation modeling (euSEM), and psychophysiological interaction (PPI) were used to investigate the interplay between the DMN and olfactory network. In the odor-visual association paradigm, DMN deactivation was evoked by both the odor + visual and visual-only trial conditions. In contrast, the visual-only trials in the no-odor paradigm did not evoke consistent DMN deactivation. In the odor-visual association paradigm, the euSEM and PPI analyses identified a directed connectivity between the DMN and olfactory network which was significantly different between odor + visual and visual-only trial conditions. The results support a strong interaction between the DMN and olfactory network and highlights the DMN's role in task-evoked brain activity and behavioral responses during olfactory processing. Hum Brain Mapp 38:1125-1139, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals
Marron, Tali R; Lerner, Yulia; Berant, Ety; Kinreich, Sivan; Shapira-Lichter, Irit; Hendler, Talma; Faust, Miriam
Research on creativity shows that creative thinking entails both executive (controlled) and associative (spontaneous) processes. Yet standard creativity tasks cannot reliably isolate these two types of cognitive processes, making it difficult to understand the relation between the two and the roles of their corresponding brain networks in creative cognition. In this study we used a behavioral and neuroimaging approach in an effort to establish chain free association (FA) tasks as a relevant method for directly investigating spontaneous associative thinking and its role in creative cognition. We further examined the relation between performance on such tasks and intelligence. Participants completed common creativity tasks and then underwent fMRI scanning while producing FA chains. Instructions to participants that emphasized the spontaneous nature of the task, coupled with proper control conditions that were balanced for difficulty, enabled us to uncover spontaneous (as opposed to controlled) processes. To examine whether behavioral measures that can be derived from FA chains (associative fluency, associative flexibility and semantic remoteness between associations) are indicative of unconstrained spontaneous associative processing and are related to different aspects of verbal creativity and intelligence, scores on these measures were correlated with scores on creativity tasks and on an intelligence task, and with brain activity. We found that: (1) the Default Mode Network (DMN), a network involved in self-generated and internally-directed thought, was more involved in chain FA than in other tasks expected to reflect more controlled forms of internally-directed thought, suggesting that the DMN involvement might be related to the unconstrained spontaneous nature of chain FA. Higher involvement of the left IFG, SFG, MFG under chain FA was also revealed; (2) higher scores on different behavioral measures from FA chains were related to higher activation of the DMN and
Full Text Available Abstract Background Reduction of mortality and morbidity from vaccine-preventable diseases in developing countries involves successfully implementing strategies that ensure high coverage and minimize drop-outs and missed opportunities. Achieving maximum coverage, however, has been a challenge due to many reasons, including high rates of defaulters from the program. The objective of this study was to explore the reasons behind defaulting from the immunization program. Methods A qualitative study was conducted in two districts of Hadiya zone, Southern Ethiopia between November 2014 and April 2015. A total of twenty-six in-depth interviews were held with mothers of defaulted children aged 6-11months old and key informants from the communities, health centers, and health offices. Observations and review of relevant documents were also conducted. Thematic analysis was used to analyze the data. Results In this study, the main reason for defaulting from the immunization was inadequate counseling of mothers that led to a lack of information about vaccination schedules and service arrangements, including in unusual circumstances such as after missed appointment, loss of vaccination card and when the health workers failed to make home visits. Provider-client relationships are poor with mothers reporting fear of mistreatment and lack of cooperation from service providers. Contrary to what health workers and managers believe, mothers were knowledgeable about the benefits of vaccination. The high workload on mothers compounded by the lack of support from male partners was also found to contribute to the problem. Health system factors that contributed to the problem were poorly arranged and coordinated immunization services, vaccine and supplies stock outs, and lack of viable defaulter tracking systems in the health facilities. Conclusions The main reasons for defaulting from the immunization program are poor counseling of mothers, unsupportive provider
Collier, Rachael; Quinlivan, Julie A
Domestic violence is common in women and is associated with poorer health-care outcomes. However, no causal pathway has been identified to explain this observation. We have followed a cohort of women to determine whether poorer outcomes can be explained by high rates of default and loss to follow-up. A prospective cohort study was performed. Institutional ethics approval was obtained. Participants were consecutive patients attending colposcopy clinics at a major metropolitan hospital in Australia. Following ascertainment of domestic violence status, appointment outcomes for colposcopy services were tracked for a 3-year period. Multivariate analysis was undertaken to determine demographic factors associated with default from care and loss to follow-up. Of 581 women approached, consent was obtained from 574 women (99%). Domestic violence status was obtained from 566 women, of whom 187 (33%) had a recent history of exposure. Women exposed to violence were more likely to default from colposcopy once (26.2% vs 7.4%; P domestic violence remained significantly associated with default and loss to follow-up. Domestic violence is a risk factor for default from attendance and loss to follow-up at colposcopy services. This may explain the mechanism behind adverse health-care outcomes seen. Screening and targeted appointment intervention programs may improve clinical compliance. © 2014 The Authors. Journal of Obstetrics and Gynaecology Research © 2014 Japan Society of Obstetrics and Gynecology.
Gao, Wei; Gilmore, John H; Alcauter, Sarael; Lin, Weili
The default-mode network has been reported to possess highly versatile and even contrasting functions but the underlying functioning mechanism remains elusive. In this study, we adopt a dynamic view of the default-mode network structure and hypothesize that it could potentially contribute to different functions through dynamic reorganization of its functional interaction pattern within and across network boundaries depending on the ongoing cognitive demands. With four experimental states and functional connectivity magnetic resonance imaging, we show that the default-mode network is characterized by within-network desynchronization and outside-network integration during the transition from resting state to an external visual classification task. Such default-mode network dynamics are task demand-dependent and return to their original status during the transition back to resting. More importantly, the degree of within-network desynchronization correlates with reaction time while the level of outside-network integration indexes task performance accuracy. Overall, the documented dynamic reorganization of the default-mode network and the significant behavioral correlations provide new insights into our understanding of this complex network and emphasize a dynamic view in future studies of its functioning mechanism.
Franciotti, Raffaella; Delli Pizzi, Stefano; Perfetti, Bernardo; Tartaro, Armando; Bonanni, Laura; Thomas, Astrid; Weis, Luca; Biundo, Roberta; Antonini, Angelo; Onofrj, Marco
Studying default mode network activity or connectivity in different parkinsonisms, with or without visual hallucinations, could highlight its roles in clinical phenotypes' expression. Multiple system atrophy is the archetype of parkinsonism without visual hallucinations, variably appearing instead in Parkinson's disease (PD). We aimed to evaluate default mode network functions in multiple system atrophy in comparison with PD. Functional magnetic resonance imaging evaluated default mode network activity and connectivity in 15 multiple system atrophy patients, 15 healthy controls, 15 early PD patients matched for disease duration, 30 severe PD patients (15 with and 15 without visual hallucinations), matched with multiple system atrophy for disease severity. Cortical thickness and neuropsychological evaluations were also performed. Multiple system atrophy had reduced default mode network activity compared with controls and PD with hallucinations, and no differences with PD (early or severe) without hallucinations. In PD with visual hallucinations, activity and connectivity was preserved compared with controls and higher than in other groups. In early PD, connectivity was lower than in controls but higher than in multiple system atrophy and severe PD without hallucinations. Cortical thickness was reduced in severe PD, with and without hallucinations, and correlated only with disease duration. Higher anxiety scores were found in patients without hallucinations. Default mode network activity and connectivity was higher in PD with visual hallucinations and reduced in multiple system atrophy and PD without visual hallucinations. Cortical thickness comparisons suggest that functional, rather than structural, changes underlie the activity and connectivity differences. © 2015 International Parkinson and Movement Disorder Society.
Kim, Seung Jun; Kim, Sung Eun; Kim, Hyo Eun; Han, Kiwan; Jeong, Bumseok; Kim, Jae Jin; Namkoong, Kee; Kim, Ji Woong
Empathy is the ability to identify with or make a vicariously experience of another person's feelings or thoughts based on memory and/or self-referential mental simulation. The default mode network in particular is related to self-referential empathy. In order to elucidate the possible neural mechanisms underlying empathy, we investigated the functional connectivity of the default mode network in subjects from a general population. Resting state functional magnetic resonance imaging data were acquired from 19 low-empathy subjects and 18 medium-empathy subjects. An independent component analysis was used to identify the default mode network, and differences in functional connectivity strength were compared between the two groups. The low-empathy group showed lower functional connectivity of the medial prefrontal cortex and anterior cingulate cortex (Brodmann areas 9 and 32) within the default mode network, compared to the medium-empathy group. The results of the present study suggest that empathy is related to functional connectivity of the medial prefrontal cortex/anterior cingulate cortex within the default mode network. Functional decreases in connectivity among low-empathy subjects may reflect an impairment of self-referential mental simulation. © Copyright: Yonsei University College of Medicine 2017.
Hearne, Luke; Cocchi, Luca; Zalesky, Andrew; Mattingley, Jason B
Successful performance of challenging cognitive tasks depends on a consistent functional segregation of activity within the default-mode network, on the one hand, and control networks encompassing frontoparietal and cingulo-opercular areas on the other. Recent work, however, has suggested that in some cognitive control contexts nodes within the default-mode and control networks may actually cooperate to achieve optimal task performance. Here, we used functional magnetic resonance imaging to examine whether the ability to relate variables while solving a cognitive reasoning problem involves transient increases in connectivity between default-mode and control regions. Participants performed a modified version of the classic Wason selection task, in which the number of variables to be related is systematically varied across trials. As expected, areas within the default-mode network showed a parametric deactivation with increases in relational complexity, compared with neural activity in null trials. Critically, some of these areas also showed enhanced connectivity with task-positive control regions. Specifically, task-based connectivity between the striatum and the angular gyri, and between the thalamus and right temporal pole, increased as a function of relational complexity. These findings challenge the notion that functional segregation between regions within default-mode and control networks invariably support cognitive task performance, and reveal previously unknown roles for the striatum and thalamus in managing network dynamics during cognitive reasoning. © 2015 Wiley Periodicals, Inc.
Frings, Lars; Schulze-Bonhage, Andreas; Spreer, Joachim; Wagner, Kathrin
In the healthy human brain the hippocampus is known to work in concert with a variety of cortical brain regions. It has recently been linked to the default network of the brain, with the precuneus being its core hub. Here we studied the remote effects of damage to the hippocampus on functional connectivity patterns of the precuneus. From 14 epilepsy patients with selective, unilateral hippocampal sclerosis and 8 healthy control subjects, we acquired functional MRI data during performance of an object-location memory task. We assessed functional connectivity of a functionally defined region in the precuneus, which showed the typical properties of the default network: significant task-related deactivation, which was reduced in patients compared to control subjects. In control subjects, a largely symmetrical pattern of functional coherence to the precuneus emerged, including canonical default network areas such as ventral medial prefrontal cortex, inferior parietal cortex, and the hippocampi. Assessment of group differences within the default network areas revealed reduced connectivity to the precuneus in ipsilesional middle temporal gyrus and hippocampus in left hippocampal sclerosis patients compared to controls. Furthermore, left hippocampal sclerosis patients showed lower connectivity than right hippocampal sclerosis patients in left middle temporal gyrus, ventral medial prefrontal cortex, and left amygdala. We report remote effects of unilateral hippocampal damage on functional connectivity between distant brain regions associated with the default network of the human brain. These preliminary results underline the impact of circumscribed pathology on functionally connected brain regions.
Pinheiro, Rejane Sobrino; Andrade, Vanusa de Lemos; Oliveira, Gisele Pinto de
This study aimed to analyze underreporting of tuberculosis (TB) cases in the Information System on Notifiable Diseases (SINAN), based on the following data sources: Mortality Information System (SIM), Registry and Follow-up Book for TB Case Treatment (LPATB), and Laboratory Registry Book (LRLAB). Probabilistic record linkage was used between the SIM (2007-2008) and SINAN (2002-2008). A search was conducted in LPATB and LRLAB (2007-2008) for cases not recorded in SINAN. There were 125 deaths, of which 44.8% were not recorded in SINAN. In LPATB, 58 cases (5.1%) were in treatment and were not reported in SINAN. LRLAB showed 32 smear-positive cases not reported to SINAN and without treatment, representing primary default. Addition of the retrieved cases, led to a 14.6% increase in the incidence rate in 2007 and 11.6% in 2008. Underreporting of deaths from or with TB in the Mortality Information System and primary default revealed difficulties in access to adequate and timely treatment, calling for rethinking of strategies to detect cases for timely treatment.
Radnitz, Cynthia; Loeb, Katharine L; DiMatteo, Julie; Keller, Kathleen L; Zucker, Nancy; Schwartz, Marlene B
The term "optimal defaults" refers to imparting pre-selected choices which are designed to produce a desired behavior change. The concept is attractive to policymakers because it steers people toward desirable behaviors while preserving free choice through the ability to opt out. It has been found to be a powerful behavioral determinant in areas such as pension plan enrollment, organ donation, and green energy utilization. We discuss how optimal defaults can be applied to pediatric obesity prevention in several domains including public policy, institutional, private sector, and home environment. Although there are obstacles to overcome in implementing optimal defaults, it is a promising component to incorporate in a multi-level strategy for preventing pediatric obesity.
Full Text Available This paper analyses the relationships between the traditional bank risk profile indicators and a new measure of banks’ probability of default that considers the Basel regulatory framework. First, based on the SYstemic Model of Bank Originated Losses (SYMBOL, we calculated the individual probabilities of default (PD of a representative sample of Spanish credit institutions during the period of 2008–2016. Then, panel data regressions were estimated to explore the influence of the risk indicators on the PD. Our findings on the Spanish banking system could be important to regulatory and supervisory authorities. First, the PD based on the SYMBOL model could be used to analyse bank risk from a regulatory approach. Second, the results might be useful for designing new regulations focused on the key factors that affect the banks’ probability of default. Third, our findings reveal that the emphasis on regulation and supervision should differ by type of entity.
Katz, Yuri A.; Tian, Li
We study the probability distributions of daily leverage returns of 520 North American industrial companies that survive de-listing during the financial crisis, 2006-2012. We provide evidence that distributions of unbiased leverage returns of all individual firms belong to the class of q-Gaussian distributions with the Tsallis entropic parameter within the interval 1develop a q-Gaussian generalization of traditional structural models of default. Derived exact analytical expressions for the probability distribution of a first stopping time and its intensity forecast significantly higher probability of default and much wider credit spreads at short time-horizons. Our findings are broadly consistent with the results of empirical studies in equity markets and are essential for single-name default forecasting as well as valuations of portfolio credit risk and economic capital, which might be underestimated by a classic theory of diversified portfolio optimization.
Andrews-Hanna, Jessica R.
During the many idle moments that comprise daily life, the human brain increases its activity across a set of midline and lateral cortical brain regions known as the “default network.” Despite the robustness with which the brain defaults to this pattern of activity, surprisingly little is known about the network’s precise anatomical organization and adaptive functions. To provide insight into these questions, this article synthesizes recent literature from structural and functional imaging with a growing behavioral literature on mind wandering. Results characterize the default network as a set of interacting hubs and subsystems that play an important role in “internal mentation” – the introspective and adaptive mental activities in which humans spontaneously and deliberately engage in everyday. . PMID:21677128
Full Text Available This paper explores the impact of corporate governance on the demand for intermediated debt (asset finance, bank debt, non-bank private debt and non-intermediated debt (public debt in the Australian debt market. Relative to other countries the Australian debt market is characterised by higher proportions of intermediated or private debt with a lower inherent level of information asymmetry in that private lenders have greater access to financial information (Gray, Koh & Tong 2009. Our firm level, cross-sectional evidence suggests that higher corporate governance impacts demand for debt via the mitigation of default risk. However, this relationship is not uniform across all debt types. Intermediated debt such as bank and asset finance debt are more responsive to changes in governance-default risk relationship than non-bank and non-intermediated debt. The implication is that a firm’s demand for different debt types will reflect its governance-default risk profile.
The much studied case of Moore v. Regents of the University of California is often considered important in property law for denying property rights in human tissue. This widespread misunderstanding of Moore has not only misplaced the legal emphasis of human tissue donations on property law instead of contract law, but has also hindered the creation of a much-needed default rule governing the issue of compensation for donated tissue. While it is possible that the majority of donors rarely consider compensation as an incentive to donate, without a legally recognized default rule the law remains blurred as to what contractual provisions apply to the exchange between donor and researcher. This Article argues that the solution is a weak default rule of no compensation that may be overridden by evidence that the parties intended otherwise.
Kodama, Hitoshi; Miyata, Yoshimasa; Kuwajima, Mami; Izuchi, Ryoichi; Kobayashi, Ayumi; Gyoja, Fuki; Onuma, Takeshi A; Kumano, Gaku; Nishida, Hiroki
During embryonic induction, the responding cells invoke an induced developmental program, whereas in the absence of an inducing signal, they assume a default uninduced cell fate. Suppression of the default fate during the inductive event is crucial for choice of the binary cell fate. In contrast to the mechanisms that promote an induced cell fate, those that suppress the default fate have been overlooked. Upon induction, intracellular signal transduction results in activation of genes encoding key transcription factors for induced tissue differentiation. It is elusive whether an induced key transcription factor has dual functions involving suppression of the default fates and promotion of the induced fate, or whether suppression of the default fate is independently regulated by other factors that are also downstream of the signaling cascade. We show that during ascidian embryonic induction, default fates were suppressed by multifold redundant mechanisms. The key transcription factor, Twist-related.a, which is required for mesenchyme differentiation, and another independent transcription factor, Lhx3, which is dispensable for mesenchyme differentiation, sequentially and redundantly suppress the default muscle fate in induced mesenchyme cells. Similarly in notochord induction, Brachyury, which is required for notochord differentiation, and other factors, Lhx3 and Mnx, are likely to suppress the default nerve cord fate redundantly. Lhx3 commonly suppresses the default fates in two kinds of induction. Mis-activation of the autonomously executed default program in induced cells is detrimental to choice of the binary cell fate. Multifold redundant mechanisms would be required for suppression of the default fate to be secure. Copyright © 2016 Elsevier Inc. All rights reserved.
Putcha, Deepti; Ross, Robert S; Cronin-Golomb, Alice; Janes, Amy C; Stern, Chantal E
Cognitive impairment is common in Parkinson's disease (PD). Three neurocognitive networks support efficient cognition: the salience network, the default mode network, and the central executive network. The salience network is thought to switch between activating and deactivating the default mode and central executive networks. Anti-correlated interactions between the salience and default mode networks in particular are necessary for efficient cognition. Our previous work demonstrated altered functional coupling between the neurocognitive networks in non-demented individuals with PD compared to age-matched control participants. Here, we aim to identify associations between cognition and functional coupling between these neurocognitive networks in the same group of participants. We investigated the extent to which intrinsic functional coupling among these neurocognitive networks is related to cognitive performance across three neuropsychological domains: executive functioning, psychomotor speed, and verbal memory. Twenty-four non-demented individuals with mild to moderate PD and 20 control participants were scanned at rest and evaluated on three neuropsychological domains. PD participants were impaired on tests from all three domains compared to control participants. Our imaging results demonstrated that successful cognition across healthy aging and Parkinson's disease participants was related to anti-correlated coupling between the salience and default mode networks. Individuals with poorer performance scores across groups demonstrated more positive salience network/default-mode network coupling. Successful cognition relies on healthy coupling between the salience and default mode networks, which may become dysfunctional in PD. These results can help inform non-pharmacological interventions (repetitive transcranial magnetic stimulation) targeting these specific networks before they become vulnerable in early stages of Parkinson's disease.
Yang, Zhi; Chang, Catie; Xu, Ting; Jiang, Lili; Handwerker, Daniel A; Castellanos, F Xavier; Milham, Michael P; Bandettini, Peter A; Zuo, Xi-Nian
The default network of the human brain has drawn much attention due to its relevance to various brain disorders, cognition, and behavior. However, its functional components and boundaries have not been precisely defined. There is no consensus as to whether the precuneus, a hub in the functional connectome, acts as part of the default network. This discrepancy is more critical for brain development and aging studies: it is not clear whether age has a stronger impact on the default network or precuneus, or both. We used Generalized Ranking and Averaging Independent Component Analysis by Reproducibility (gRAICAR) to investigate the lifespan trajectories of intrinsic functional networks. By estimating individual-specific spatial components and aligning them across subjects, gRAICAR measures the spatial variation of component maps across a population without constraining the same components to appear in every subject. In a cross-lifespan fMRI dataset (N=126, 7-85years old), we observed stronger age dependence in the spatial pattern of a precuneus-dorsal posterior cingulate cortex network compared to the default network, despite the fact that the two networks exhibit considerable spatial overlap and temporal correlation. These results remained even when analyses were restricted to a subpopulation with very similar head motion across age. Our analyses further showed that the two networks tend to merge with increasing age. Post-hoc analyses of functional connectivity confirmed the distinguishable cross-lifespan trajectories between the two networks. Based on these observations, we proposed a dynamic model of cross-lifespan functional segregation and integration between the two networks, suggesting that the precuneus network may have a different functional role than the default network, which declines with age. These findings have implications for understanding the functional roles of the default network, gaining insight into its dynamics throughout life, and guiding
Mindy Leow; Christophe Mues; Lyn Thomas
Loss given default (LGD) models predict losses as a proportion of the outstanding loan, in the event a debtor goes into default. The literature on corporate sector LGD models suggests LGD is correlated to the economy and so changes in the economy could translate into different predictions of losses. In this work, the role of macroeconomic variables in loan-level retail LGD models is examined by testing the inclusion of macroeconomic variables in two different retail LGD models: a two-stage mo...
An, Z.G.; Mniszewski, S.M.; Lee, Y.C.; Papcun, G.; Doolen, G.D.
A new learning algorithm based on a default hierarchy of high order neural networks has been developed that is able to generalize as well as handle exceptions. It learns the ''building blocks'' or clusters of symbols in a stream that appear repeatedly and convey certain messages. The default hierarchy prevents a combinatoric explosion of rules. A simulator of such a hierarchy, HIERtalker, has been applied to the conversion of English words to phonemes. Achieved accuracy is 99% for trained words and ranges from 76% to 96% for sets of new words. 8 refs., 4 figs., 1 tab.
Full Text Available The aim of this paper is the measurement of currency mismatch for a selected group of developing and frontier markets in the Central and Eastern Europe and Western Balkan regions and the analysis of the effects of aggregate currency misbalances on particular countries’ risk of default. The empirical tests provided confirm the positive effect of currency mismatch on default risk, which is reflected in the behaviour of yield spreads on the government bonds of the countries under consideration. The higher the negative currency misbalances are, the higher the EMBI spreads appear to be, and vice versa.
phase. Independent predictors of poor outcome were partial DOT (adjusted risk ratio (aRR) 3.1, 95% confidence interval (CI) 2.2 - 4.3) and previous treatment default (aRR 2.3, 95% CI 1.1 - 4.8). Conclusion. Patients who received incomplete DOT or had a history of defaulting from TB treatment had an increased risk of poor.
Tsagouli, Paraskevi; Sotiropoulou, Evagelia; Filippousis, Petros; Sidiropoulou, Nektaria; Georgiadi, Vithleem; Thanos, Loukas
Purpose: To determine the efficiency and safety of the percutaneous aspiration and drainage of rare touberculous cold abscesses under CT guidance. Materials and methods: We retrospectively studied 63 cases of 44 patients, treated in our hospital during the last two years. They suffered from tuberculous infection complicated with tuberculous cold abscesses variously located. All these patients underwent percutaneous aspiration and drainage under CT imaging, following the trocar puncture technique. The catheter remained in place for about a week. A follow up CT scan was performed in all cases before the catheter removal. Some of the patients were under anti tuberculosis medication. Results: All the patients had a successful recovery from the abscesses. There were no major or minor complications observed. No recurrence occurred until today. Conclusion: CT guided percutaneous aspiration and drainage of tuberculous cold abscesses is a safe, minimal invasive and effective method of treatment. Drainage and specific antituberculosis therapy leads to a satisfactory conclusion.
G. N. Mozhokina
Full Text Available The article presents the analysis of the literature on specific metabolism of anti-tuberculosis drugs depending on polymorphism of genes controlling synthesis and action of biotransformation enzymes, in particular cytochrome P-450 isozymes and enzymes of the IInd phase of biotransformation (N-acetyltransferase, glutathione S-transferase respective adverse reactions development, first of all hepatotoxic ones. The possibility of pharmacogenetic studies with the evaluation of genetic predisposition to developing adverse reactions to medications has been discussed in respect of personalized approach to effective and safe treatment of tuberculosis patients.
Mak, Lauren E; Minuzzi, Luciano; MacQueen, Glenda; Hall, Geoffrey; Kennedy, Sidney H; Milev, Roumen
When the brain is not engaged in goal-directed activities and at rest, there are still measureable patterns of activity. One resting-state network, the default mode network (DMN) is responsible for a self-referential introspective state. There are many factors that influence normal changes in brain activity. The purpose of this review is to summarize differences in DMN functional connectivity in healthy individuals by age, sex, cognitive function, and analysis type to characterize what is "normal." Studies were systematically selected up to August 2016. Two reviewers independently used predetermined inclusion and exclusion criteria to identify relevant studies. Studies that provided sufficient information were included in a subsequent voxel-wise meta-analysis. Strength of DMN functional connectivity follows an inverse U-shape, where it is strongest in adulthood and lowest in children and elderly. Cognitive function is positively correlated with DMN functional connectivity. Females exhibit stronger intranetwork connectivity compared with males. Effects of analysis type were inconclusive and more studies need to incorporate complementing techniques. The voxel-wise meta-analysis was only conducted for the age factor. Findings supported an immature network in children compared with adults and a stronger network in adults compared with elderly. This is the first study to review differences of DMN functional connectivity in healthy individuals by age, sex, cognitive function, and analysis type. Findings add to the understanding of normal variance. Furthermore, defining a normal comparative base may allow for the identification of DMN change into pathology. This is important since it may allow for the detection of an intermediate risk phenotype and could serve as a biomarker for treatment response.
Kim, Sun Mi; Park, Sung Yong; Kim, Young In; Son, Young Don; Chung, Un-Sun; Min, Kyung Joon; Han, Doug Hyun
Disruptive behaviors are thought to affect the progress of major depressive disorder (MDD) in adolescents. In resting-state functional connectivity (RSFC) studies of MDD, the affective network (limbic network) and the default mode network (DMN) have garnered a great deal of interest. We aimed to investigate RSFC in a sample of treatment-naïve adolescents with MDD and disruptive behaviors. Twenty-two adolescents with MDD and disruptive behaviors (disrup-MDD) and 20 age- and sex-matched healthy control (HC) participants underwent resting-state functional magnetic resonance imaging (fMRI). We used a seed-based correlation approach concerning two brain circuits including the affective network and the DMN, with two seed regions including the bilateral amygdala for the limbic network and the bilateral posterior cingulate cortex (PCC) for the DMN. We also observed a correlation between RSFC and severity of depressive symptoms and disruptive behaviors. The disrup-MDD participants showed lower RSFC from the amygdala to the orbitofrontal cortex and parahippocampal gyrus compared to HC participants. Depression scores in disrup-MDD participants were negatively correlated with RSFC from the amygdala to the right orbitofrontal cortex. The disrup-MDD participants had higher PCC RSFC compared to HC participants in a cluster that included the left precentral gyrus, left insula, and left parietal lobe. Disruptive behavior scores in disrup-MDD patients were positively correlated with RSFC from the PCC to the left insular cortex. Depressive mood might be correlated with the affective network, and disruptive behavior might be correlated with the DMN in adolescent depression.
Nelson, G [University of Wisconsin, Madison, WI (United States)
Purpose CBCT is being increasingly used in patient setup for radiotherapy. Often the manufacturer default scan modes are used for performing these CBCT scans with the assumption that they are the best options. To quantitatively assess the image quality of these scan modes, all of the scan modes were tested as well as options with the reconstruction algorithm. Methods A CatPhan 504 phantom was scanned on a TrueBeam Linear Accelerator using the manufacturer scan modes (FSRT Head, Head, Image Gently, Pelvis, Pelvis Obese, Spotlight, & Thorax). The Head mode scan was then reconstructed multiple times with all filter options (Smooth, Standard, Sharp, & Ultra Sharp) and all Ring Suppression options (Disabled, Weak, Medium, & Strong). An open source ImageJ tool was created for analyzing the CatPhan 504 images. Results The MTF curve was primarily dictated by the voxel size and the filter used in the reconstruction algorithm. The filters also impact the image noise. The CNR was worst for the Image Gently mode, followed by FSRT Head and Head. The sharper the filter, the worse the CNR. HU varied significantly between scan modes. Pelvis Obese had lower than expected HU values than most while the Image Gently mode had higher than expected HU values. If a therapist tried to use preset window and level settings, they would not show the desired tissue for some scan modes. Conclusion Knowing the image quality of the set scan modes, will enable users to better optimize their setup CBCT. Evaluation of the scan mode image quality could improve setup efficiency and lead to better treatment outcomes.
The Department of Education (Education) relies on collection agencies to assist borrowers in rehabilitating defaulted student loans, which allows borrowers who make nine on-time monthly payments within 10 months to have the default removed from their credit reports. Education works with 22 collection agencies to locate borrowers and explain…
Koopman, S.J.; Lucas, A.; Schwaab, B.
We develop a high-dimensional, nonlinear, and non-Gaussian dynamic factor model for the decomposition of systematic default risk conditions into latent components for (1) macroeconomic/financial risk, (2) autonomous default dynamics (frailty), and (3) industry-specific effects. We analyze discrete
... projects). (a) Rights of Owner if PHA defaults under Agreement or Contract. The ACC, the Agreement and the... obligations to enter into the Contract. (b) Rights of HUD if PHA defaults under ACC. The ACC will provide that..., HUD will continue to pay annual contributions in accordance with the terms of the ACC and the Contract...
Han, Doug Hyun; Kim, Sun Mi; Bae, Sujin; Renshaw, Perry F; Anderson, Jeffrey S
Individuals who are chronic, compulsive video game players experience an elevated incidence of major depression. Excessive or problematic game play can interact with depression clinically, and may magnify impulsive behavior associated with video gaming. Functional brain imaging was performed during a Wisconsin Card Sorting Test (WCST) task in 42 healthy control and 95 volunteers seeking treatment for compulsive video game playing, including 60 participants without major depression (pure internet gaming disorder, pure IGD) and 35 participants comorbid with major depression (IGD+MDD). In response to the WCST in contrast to fixation, activation was observed in canonical brain attentional networks including bilateral intraparietal sulcus, frontal eye fields, and middle temporal cortical regions as well as dorsolateral prefrontal, inferior parietal and anterior insula, anterior cingulate cortex in all participants. For WCST>Fixation contrasts, the IGD+MDD group exhibited greater relative activation within the left hippocampus, compared to healthy control participants. For WCST>Fixation contrasts, the IGD+MDD group exhibited greater relative activation within the left hippocampus and the right parahippocampal gyrus immediately posterior to the hippocampus, compared to the pure IGD group. In cohorts of individuals with a history of compulsive internet game play, individuals with depression showed failure to suppress default mode network activity during an attentionally demanding task, compared to individuals without depression, including comparison groups with and without a history of compulsive video gaming. This reduced suppression of the brain regions within the default mode network may be a consequence of depressive neurophysiology or represent a predisposition for depression within compulsive game players. Copyright © 2016 Elsevier B.V. All rights reserved.
Cui, Ying; Jiao, Yun; Chen, Hua-Jun; Ding, Jie; Luo, Bing; Peng, Cheng-Yu; Ju, Sheng-Hong; Teng, Gao-Jun
Type 2 diabetes mellitus is associated with increased risk for dementia. Patients with impaired cognition often show default-mode network disruption. We aimed to investigate the integrity of a default-mode network in diabetic patients by using independent component analysis, and to explore the relationship between network abnormalities, neurocognitive performance and diabetic variables. Forty-two patients with type 2 diabetes and 42 well-matched healthy controls were included and underwent resting-state functional MRI in a 3 Tesla unit. Independent component analysis was adopted to extract the default-mode network, including its anterior and posterior components. Z-maps of both sub-networks were compared between the two groups and correlated with each clinical variable. Patients showed increased connectivity around the medial prefrontal cortex in the anterior sub-network, but decreased connectivity around the posterior cingulate cortex in the posterior sub-network. The decreased connectivity in the posterior part was significantly correlated with the score on Complex Figure Test-delay recall test (r = 0.359, p = 0.020), the time spent on Trail-Making Test-part B (r = -0.346, p = 0.025) and the insulin resistance level (r = -0.404, p = 0.024). Dissociation pattern in the default-mode network was found in diabetic patients, which might provide powerful new insights into the neural mechanisms that underlie the diabetes-related cognitive decline. (orig.)
Matthijs G Bossong
Full Text Available Evidence is increasing for involvement of the endocannabinoid system in cognitive functions including attention and executive function, as well as in psychiatric disorders characterized by cognitive deficits, such as schizophrenia. Executive function appears to be associated with both modulation of active networks and inhibition of activity in the default mode network. In the present study, we examined the role of the endocannabinoid system in executive function, focusing on both the associated brain network and the default mode network. A pharmacological functional magnetic resonance imaging (fMRI study was conducted with a placebo-controlled, cross-over design, investigating effects of the endocannabinoid agonist Δ9-tetrahydrocannabinol (THC on executive function in 20 healthy volunteers, using a continuous performance task with identical pairs. Task performance was impaired after THC administration, reflected in both an increase in false alarms and a reduction in detected targets. This was associated with reduced deactivation in a set of brain regions linked to the default mode network, including posterior cingulate cortex and angular gyrus. Less deactivation was significantly correlated with lower performance after THC. Regions that were activated by the continuous performance task, notably bilateral prefrontal and parietal cortex, did not show effects of THC. These findings suggest an important role for the endocannabinoid system in both default mode modulation and executive function. This may be relevant for psychiatric disorders associated with executive function deficits, such as schizophrenia and ADHD.
Brown, Scott R.
The recent housing crisis has generated debate over the benefits and risks of policies and programs promoting homeownership for low and moderate income households. One important facet of this conversation is whether prepurchase homebuyer education (HBE) is effective in reducing default or foreclosure risk. Studies to date have primarily focused on…
Renner, F.; Siep, N.; Arntz, A.; van de Ven, V.; Peeters, F.P.M.L.; Quaedflieg, C.W.E.M.; Huibers, M.J.H.
BACKGROUND: The aim of this study was to investigate the effects of sad mood on default mode network (DMN) resting-state connectivity in persons with chronic major depressive disorder (cMDD). METHODS: Participants with a diagnosis of cMDD (n=18) and age, gender and education level matched
Liemburg, Edith J.; Swart, Marte; Bruggeman, Richard; Kortekaas, Rudie; Knegtering, Henderikus; Curcic-Blake, Branislava; Aleman, Andre
Alexithymia is a trait characterized by a diminished capacity to describe and distinguish emotions and to fantasize; it is associated with reduced introspection and problems in emotion processing. The default mode network (DMN) is a network of brain areas that is normally active during rest and
Zhang, Jilei; Su, Jingjing; Wang, Mengxing; Zhao, Ying; Yao, Qian; Zhang, Qiting; Lu, Haifeng; Zhang, Hui; Wang, Shuo; Li, Ge-Fei; Wu, Yi-Lan; Liu, Feng-Di; Shi, Yan-Hui; Li, Jianqi; Liu, Jian-Ren; Du, Xiaoxia
The precuneus/posterior cingulate cortex, which has been associated with pain sensitivity, plays a pivotal role in the default mode network. However, information regarding migraine-related alterations in resting-state brain functional connectivity in the default mode network and in local regional spontaneous neuronal activity is not adequate. This study used functional magnetic resonance imaging to acquire resting-state scans in 22 migraineurs without aura and in 22 healthy matched controls. Independent component analysis, a data-driven method, was used to calculate the resting-state functional connectivity of the default mode network in the patient and healthy control groups. Regional homogeneity (ReHo) was used to analyse the local features of spontaneous resting-state brain activity in the migraineurs without aura. Compared with the healthy controls, migraineurs without aura showed increased functional connectivity in the left precuneus/posterior cingulate cortex within the default mode network and significant increase in ReHo values in the bilateral precuneus/posterior cingulate cortex, left pons and trigeminal nerve entry zone. In addition, functional connectivity was decreased between the areas with abnormal ReHo (using the peaks in the precuneus/posterior cingulate cortex) and other brain areas. The abnormalities in the precuneus/posterior cingulate cortex suggest that migraineurs without aura may exhibit information transfer and multimodal integration dysfunction and that pain sensitivity and pian processing may also be affected.
Zhang, Shanshan; Wu, Wen; Huang, Guozhi; Liu, Ziping; Guo, Shigui; Yang, Jianming; Wang, Kangling
Functional magnetic resonance imaging studies have shown that the insular cortex has a significant role in pain identification and information integration, while the default mode network is associated with cognitive and memory-related aspects of pain perception. However, changes in the functional connectivity between the default mode network and insula during pain remain unclear. This study used 3.0 T functional magnetic resonance imaging scans in 12 healthy subjects aged 24.8 ± 3.3 years to compare the differences in the functional activity and connectivity of the insula and default mode network between the baseline and pain condition induced by intramuscular injection of hypertonic saline. Compared with the baseline, the insula was more functionally connected with the medial prefrontal and lateral temporal cortices, whereas there was lower connectivity with the posterior cingulate cortex, precuneus and inferior parietal lobule in the pain condition. In addition, compared with baseline, the anterior cingulate cortex exhibited greater connectivity with the posterior insula, but lower connectivity with the anterior insula, during the pain condition. These data indicate that experimental low back pain led to dysfunction in the connectivity between the insula and default mode network resulting from an impairment of the regions of the brain related to cognition and emotion, suggesting the importance of the interaction between these regions in pain processing.
Mars, R.B.; Neubert, F.X.; Noonan, M.P.; Sallet, J.; Toni, I.; Rushworth, M.F.S.
The default mode network (DMN) of the brain consists of areas that are typically more active during rest than during active task performance. Recently however, this network has been shown to be activated by certain types of tasks. Social cognition, particularly higher-order tasks such as attributing
van Oort, E.S.B.; van Cappellen van Walsum, Anne-Marie; Norris, David Gordon
Connectivity analyses based on both resting-state (rs-)fMRI and diffusion weighted imaging studies suggest that the human brain contains regions that act as hubs for the entire brain, and that elements of the Default Mode Network (DMN) play a pivotal role in this network. In the present study, the
Gaffrey, Michael S.; Luby, Joan L.; Botteron, Kelly; Repovs, Grega; Barch, Deanna M.
Background: Atypical Default Mode Network (DMN) functional connectivity has been previously reported in depressed adults. However, there is relatively little data informing the developmental nature of this phenomenon. The current case-control study examined the DMN in a unique prospective sample of school-age children with a previous history of…
Wosnitza, Jan Henrik; Denz, Cornelia
We employ the log-periodic power law (LPPL) to analyze the late-2000 financial crisis from the perspective of critical phenomena. The main purpose of this study is to examine whether LPPL structures in the development of credit default swap (CDS) spreads can be used for default classification. Based on the different triggers of Bear Stearns’ near bankruptcy during the late-2000 financial crisis and Ford’s insolvency in 2009, this study provides a quantitative description of the mechanism behind bank runs. We apply the Johansen-Ledoit-Sornette (JLS) positive feedback model to explain the rise of financial institutions’ CDS spreads during the global financial crisis 2007-2009. This investigation is based on CDS spreads of 40 major banks over the period from June 2007 to April 2009 which includes a significant CDS spread increase. The qualitative data analysis indicates that the CDS spread variations have followed LPPL patterns during the global financial crisis. Furthermore, the univariate classification performances of seven LPPL parameters as default indicators are measured by Mann-Whitney U tests. The present study supports the hypothesis that discrete scale-invariance governs the dynamics of financial markets and suggests the application of new and fast updateable default indicators to capture the buildup of long-range correlations between creditors.
Zhao Xiaohu [Imaging Department of Tong Ji Hospital of Tong Ji University, Shanghai 200065 (China) and Bio-X lab, Department of Physics, Zhe Jiang University, Hangzhou 310027 (China)], E-mail: email@example.com; Wang Peijun [Imaging Department of Tong Ji Hospital of Tong Ji University, Shanghai 200065 (China)], E-mail: firstname.lastname@example.org; Li Chunbo [Department of Psychiatry, Tong Ji Hospital of Tong Ji University, Shanghai 200065 (China)], E-mail: email@example.com; Hu Zhenghui [Department of Electrical and Engineering, Hong Kong University of Science and Technology, Hong Kong (China)], E-mail: firstname.lastname@example.org; Xi Qian [Imaging Department of Tong Ji Hospital of Tong Ji University, Shanghai 200065 (China)], E-mail: email@example.com; Wu Wenyuan [Department of Psychiatry, Tong Ji Hospital of Tong Ji University, Shanghai 200065 (China)], E-mail: firstname.lastname@example.org; Tang Xiaowei [Bio-X lab, Department of Physics, Zhe Jiang University, Hangzhou 310027 (China)], E-mail: email@example.com
Anxiety disorder, a common mental disorder in our clinical practice, is characterized by unprovoked anxiety. Medial prefrontal cortex (MPFC) and posterior cingulate cortex (PCC), which closely involved in emotional processing, are critical regions in the default mode network. We used functional magnetic resonance imaging (fMRI) to investigate whether default mode network activity is altered in patients with anxiety disorder. Ten anxiety patients and 10 healthy controls underwent fMRI while listening to emotionally neutral words alternating with rest (Experiment 1) and threat-related words alternating with emotionally neutral words (Experiment 2). In Experiment 1, regions of deactivation were observed in patients and controls. In Experiment 2, regions of deactivation were observed only in patients. The observed deactivation patterns in the two experiments, which included MPFC, PCC, and inferior parietal cortex, were similar and consistent with the default model network. Less deactivation in MPFC and greater deactivation in PCC were observed for patients group comparing to controls in Experiment 1. Our observations suggest that the default model network is altered in anxiety patients and dysfunction in MPFC and PCC may play an important role in anxiety psychopathology.