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BackgroundThe World Health Organization recommends that schistosomiasis be treated through Mass Drug Administration (MDA). In line with this recommendation, Zimbabwe commenced a national helminth control program in 2012 targeting schoolchildren throughout the country for 6 years. This study, part of a larger investigation of the impact of helminth treatment on the overall health of the children, determined the effect of annual praziquantel treatment on schistosome infection and morbidity in a cohort of children during Zimbabwe's 6-year national helminth control program.Methodology/principal findingsA school-based longitudinal study was carried out in 35 sentinel sites across Zimbabwe from September 2012 to November 2017. The sentinel sites were selected following a countrywide survey conducted in 280 primary schools. Schistosoma haematobium was diagnosed using the urine filtration technique. Schistosoma mansoni was diagnosed using both the Kato-Katz and formol-ether concentration techniques. S. haematobium morbidity was determined through detection of macro and microhaematuria. A cohort of children aged 6-15 years old was surveyed annually before MDA and 6 weeks post treatment. Maximum treatment coverage reached 90% over the 6 rounds of MDA. At baseline S. haematobium infection prevalence and intensity were 31.7% (95% CI = 31.1-32.2) and 28.75 eggs/10ml urine (SEM = 0.81) respectively, while S. mansoni prevalence and intensity were 4.6% (95% CI = 4.4-4.8) and 0.28 eggs/25mg (SEM = 0.02). Prior to the 6th round of MDA, S. haematobium infection prevalence had reduced to 1.56% (pConclusionZimbabwe's helminth control program significantly reduced schistosome infection intensity and prevalence and urogenital schistosomiasis morbidity prevalence in a cohort of school-aged children, moving the schistosome prevalence in the children from moderate to low by WHO classification. These findings will inform the design of the country's next stage interventions for helminth control and eventual elimination.

Tuberculosis (TB) infections among children (below 15 years) is a growing concern, particularly in resource-limited settings. However, the TB burden among children is relatively unknown in Kenya where two-thirds of estimated TB cases are undiagnosed annually. Very few studies have used Autoregressive Integrated Moving Average (ARIMA), and hybrid ARIMA models to model infectious diseases globally. We applied ARIMA, and hybrid ARIMA models to predict and forecast TB incidences among children in Homa Bay and Turkana Counties in Kenya. The ARIMA, and hybrid models were used to predict and forecast monthly TB cases reported in the Treatment Information from Basic Unit (TIBU) system by health facilities in Homa Bay and Turkana Counties between 2012 and 2021. The best parsimonious ARIMA model that minimizes errors was selected based on a rolling window cross-validation procedure. The hybrid ARIMA-ANN model produced better predictive and forecast accuracy compared to the Seasonal ARIMA (0,0,1,1,0,1,12) model. Furthermore, using the Diebold-Mariano (DM) test, the predictive accuracy of ARIMA-ANN versus ARIMA (0,0,1,1,0,1,12) model were significantly different, p

Uvulitis is the inflammation and swelling of the uvula, usually associated with infection of nearby structures. Uvulitis can be treated symptomatically, using medication or in some cases with uvulectomy, the uvula surgical removal or shortening. Traditional uvulectomy by traditional practitioners has been practiced in Africa for ages, associated with adverse outcomes. Although there is no empirical evidence for the association between adverse outcomes and traditional uvulectomy in Uganda, anecdotal findings showed incidents of uvula infections following uvulectomy in central Uganda. While these findings also indicate that traditional uvulectomy is common, the community understanding of uvulitis, the beliefs and practices are not well understood. This qualitative study sought to understand beliefs and practices using interviews with community health workers, traditional uvulectomy clients, and traditional surgeons, and focus group discussions with community members. Transcribed data were analysed in Atlas.ti 9 using thematic analysis steps. The findings show that uvula infection, locally known as "Akamiro" and the associated traditional uvulectomy are common in Luwero and beyond. "Akamiro" was described as larger than the normal, the size of a chicken heart or a big pimple, visible when a child cries, with unknown causes. Symptoms included persistent cough, diarrhoea, vomiting, loss of appetite, inability to swallow and ultimately weight loss, swollen stomach, saliva overflow, fever, breathing and speech difficulty. Diagnosis was confirmed after seeking care from health workers or in consultation with significant others and finally the traditional surgeon; in a hierarchical pattern. Uvulectomy was conducted by traditional surgeons, with surgery lasting a few minutes, in the morning or after sun-set. Tools used were razor blades, reeds, strings, wires, sickle knives and spoons. Payment was flexible; cash or in-kind. Surgeons had immense community trust, including community health workers. Interventions to support persons with uvula infections need to address the health system weaknesses, and health education.

Communicable diseases, alone or in combination with malnutrition, account for most deaths in complex emergencies including refugee settings. Tuberculosis and HIV/AIDS are increasingly becoming an important cause of morbidity and mortality in refugee settings. We described the treatment outcomes of TB patients and explored factors associated with treatment outcomes among TB patients attending two facilities in Kyangwali Refugee Settlement in Kikuube District, 2016-2017. We abstracted data on laboratory-confirmed patient data from TB registers from 2016 to 2017, in Kikuube Health Centre IV and Rwenyawawa Health Centre II, both located in Kyangwali Refugee Settlement. We abstracted data on socio-demographic variables including age and sex. Other variables were height, weight, final treatment outcomes, demographics, HIV status, TB treatment category, and history of TB. Treatment outcomes were categorized into favorable (including patients who were cured or those who completed treatment) and unfavorable (those in whom treatment failed, those who died, those lost to follow-up, or those not evaluated). We used logistic regression to identify factors associated with unfavorable treatment outcomes. We identified a total of 254 TB patients with a median age of 36 (IQR 26-48) years; 69% (175) were male and 54% (137) were refugees. The median weight was 50.4 kg (range 4-198). Overall, 139 (55%) had favorable outcomes while 115 (45%) had unfavorable outcomes. Refugees formed 53% (71) of those with favorable outcomes and 47% (63) of those with unfavorable outcomes 63(47%). We found that increasing age was statistically associated with unfavorable outcomes, while diagnosis with MDR-TB was associated with decreased odds for unfavorable treatment outcomes. The treatment success rate was lower compared to 85% recommended by WHO. However, the rates are similar to that reported by other studies in Uganda. Innovative approaches to improve treatment success rates with particular focus on persons aged 41-80 years should be devised.

Sarcomeres, the basic contractile units of striated muscle cells, contain arrays of thin (actin) and thick (myosin) filaments that slide past each other during contraction. The Ig-like domain-containing protein myotilin provides structural integrity to Z-discs-the boundaries between adjacent sarcomeres. Myotilin binds to Z-disc components, including F-actin and α-actinin-2, but the molecular mechanism of binding and implications of these interactions on Z-disc integrity are still elusive. To illuminate them, we used a combination of small-angle X-ray scattering, cross-linking mass spectrometry, and biochemical and molecular biophysics approaches. We discovered that myotilin displays conformational ensembles in solution. We generated a structural model of the F-actin:myotilin complex that revealed how myotilin interacts with and stabilizes F-actin via its Ig-like domains and flanking regions. Mutant myotilin designed with impaired F-actin binding showed increased dynamics in cells. Structural analyses and competition assays uncovered that myotilin displaces tropomyosin from F-actin. Our findings suggest a novel role of myotilin as a co-organizer of Z-disc assembly and advance our mechanistic understanding of myotilin's structural role in Z-discs.

BackgroundCryptococcal meningitis (CCM) remains one of the leading causes of mortality among HIV infected patients. Due to factors such as the severity of CCM pathology, the quality of life (QOL) of patients post-treatment is likely to be poor. Few studies have reported on QOL of CCM patients post treatment completion. We used data collected among patients in the CryptoDex trial (ISRCTN59144167) to determine QOL and associated factors at week 10 and six months from treatment initiation.MethodologyCryptoDex was a double-blind placebo-controlled trial of adjunctive dexamethasone in HIV infected adults with CCM, conducted between 2013 and 2015 in six countries in Asia and Africa. QOL was determined using the descriptive and Visual Analog Scales (VAS) of the EuroQol Five-Dimension-Three-Level (EQ-5D-3L) tool. We derived index scores, and described these and the VAS scores at 10 weeks and 6 months; and used linear regression to determine the relationship between various characteristics and VAS scores at both time points. VAS scores were interpreted as very good (81-100), good (51-80), normal (31-50) and bad/very bad (0-30).ResultsOf 451 patients enrolled in the trial, 238 had QOL evaluations at week 10. At baseline, their mean age (SD) was 35.2(8.5) years. The mean index scores (SD) were 0.785(0.2) and 0.619(0.4) among African and Asian patients respectively at week 10, and 0.879(0.2) and 0.731(0.4) among African and Asian patients respectively at month six. The overall mean VAS score (SD) at 10 weeks was 57.2 (29.7), increasing significantly to 72(27.4) at month six (pConclusionQOL was good among patients that had completed therapy for CCM, but below perfect. Strategies to improve QOL among CCM survivors are required.

BackgroundIdentifying pain-related response patterns and understanding functional mechanisms of symptom formation and recovery are important for improving treatment.ObjectivesWe aimed to replicate pain-related avoidance-endurance response patterns associated with the Fear-Avoidance Model, and its extension, the Avoidance-Endurance Model, and examined their differences in secondary measures of stress, action control (i.e., dispositional action vs. state orientation), coping, and health.MethodsLatent profile analysis (LPA) was conducted on self-report data from 536 patients with chronic non-specific low back pain at the beginning of an inpatient rehabilitation program. Measures of stress (i.e., pain, life stress) and action control were analyzed as covariates regarding their influence on the formation of different pain response profiles. Measures of coping and health were examined as dependent variables.ResultsPartially in line with our assumptions, we found three pain response profiles of distress-avoidance, eustress-endurance, and low-endurance responses that are depending on the level of perceived stress and action control. Distress-avoidance responders emerged as the most burdened, dysfunctional patient group concerning measures of stress, action control, maladaptive coping, and health. Eustress-endurance responders showed one of the highest levels of action versus state orientation, as well as the highest levels of adaptive coping and physical activity. Low-endurance responders reported lower levels of stress as well as equal levels of action versus state orientation, maladaptive coping, and health compared to eustress-endurance responders; however, equally low levels of adaptive coping and physical activity compared to distress-avoidance responders.ConclusionsApart from the partially supported assumptions of the Fear-Avoidance and Avoidance-Endurance Model, perceived stress and dispositional action versus state orientation may play a crucial role in the formation of pain-related avoidance-endurance response patterns that vary in degree of adaptiveness. Results suggest tailoring interventions based on behavioral and functional analysis of pain responses in order to more effectively improve patients quality of life.

Globally, early initiation of antiretroviral therapy for HIV led to a reduction in the estimated mortality from cryptococcal meningitis (CCM) from 624,700 in 2009 to 181,100 in 2014. However, CCM remains one of the leading causes of mortality among HIV infected patients especially in sub-Saharan Africa where 75% of the deaths occur. Most of the studies evaluating mortality have reported short-term mortality (at or before 10 weeks of therapy). We determined mortality and associated factors among patients treated for CCM in the CryptoDex trial (ISRCTN59144167) in Uganda, and the effect of dexamethasone adjunctive therapy on mortality at two years. We conducted a retrospective cohort study between May 2017 and July 2017 to determine the long term survival (up to 2 years post-randomization) of all patients who had been enrolled into the CryptoDex trial in Uganda. The CryptoDex trial recruited between April 2013 and February 2015. We estimated mortality rates and determined factors affecting mortality at two years using Cox regression. The study followed up 211 participants, 127 (60.2%) of whom were male. Sixteen participants (7.58%) were diagnosed with HIV at the same admission when CCM was diagnosed. By two years following randomization 127 (60%) participants had died, a mortality rate of 67 deaths per 100 person-years. Mortality was associated with Glasgow coma score (GCS) below 15 (adjusted Hazard ratio (aHR) 1.77, 95% CI: 1.02-2.44), p = 0.040; weight (aHR 0.97, per 1 Kg increase; 95% CI: 0.94-0.99), p = 0.003; and presence of convulsions (aHR 2.31, 95% CI: 1.32-4.04), p = 0.004, while dexamethasone use and fungal burden had no effect. Long-term mortality in CCM patients remains high even among patients receiving recommended therapy. Strategies to improve long-term survival in CCM patients are urgently needed, especially targeting those with reduced GCS, low weight, and convulsions.

BACKGROUND:Retaining patients starting antiretroviral therapy (ART) and ensuring good adherence remain cornerstone of long-term viral suppression. In this era of test and treat (T&T) policy, ensuring that patients starting ART remain connected to HIV clinics is key to achieve the UNAIDS 90-90-90 targets. Currently, limited studies have evaluated the effect of early ART initiation on loss to follow up in a routine health care delivery setting. We studied the cumulative incidence, incidence rate of loss to follow up (LTFU), and factors associated with LTFU in a primary healthcare clinic that has practiced T&T since 2012. METHODS:We retrospectively analyzed extracted routine program data on patients who started ART from January 2012 to 4th July 2016. We defined LTFU as failure of a patient to return to the HIV clinic for at least 90 days from the date of their last appointment. We calculated cumulative incidence, incidence rate and fitted a multivariable Cox proportion hazards regression model to determine factors associated with LTFU. RESULTS:Of the 7,553 patients included in our sample, 3,231 (42.8%) started ART within seven days following HIV diagnosis. There were 1,180 cases of LTFU observed over 15,807.7 person years at risk. The overall incidence rate (IR) of LTFU was 7.5 (95% CI, 7.1-7.9) per 100 person years of observation (pyo). Cumulative incidence of LTFU increased with duration of follow up from 8.9% (95% CI, 8.2-9.6%) at 6 months to 20.2% (95% CI, 19.0-21.4%) at 48 months. Predictors of elevated risk of LTFU were: starting ART within 7 days following HIV diagnosis ((aHR) = 1.69, 95% CI, 1.50-1.91), lack of a telephone set (aHR = 1.52, 95% CI, 1.35-1.71), CD4 cell count of 200-350μ/ml (aHR = 1.21, 95% CI, 1.01-1.45) and baseline WHO clinical stage 3 or 4 (aHR = 1.35, 95% CI, 1.10-1.65). Factors associated with a reduced risk of LTFU were: baseline age ≥25 years (aHR ranging from 0.62, 95% CI, 0.47-0.81 for age group 25-29 years to 0.24, 95% CI, 0.13-0.44 for age group ≥50 years), at least primary education level (aHR ranging from aHR = 0.77, 95% CI, 0.62-0.94 for primary education level to 0.50, 95% CI, 0.34-0.75 for post-secondary education level), and having a BMI ≥ 30 (aHR = 0.28, 95% CI, 0.15-0.51). CONCLUSION:The risk of loss to follow up increased with time and was higher among patients who started ART within seven days following HIV diagnosis, higher among patients without a telephone set, lower among patients aged ≥ 25 years, lower among patients with at least primary education and lower among patients with BMI of ≥ 30. In this era of T&T, it will be important for HIV programs to initiate and continue enhanced therapeutic education programs that target high risk groups, as well as leveraging on mHealth to improve patients' retention on ART throughout the cascade of care.

MORN (Membrane Occupation and Recognition Nexus) repeat proteins have a wide taxonomic distribution, being found in both prokaryotes and eukaryotes. Despite this ubiquity, they remain poorly characterised at both a structural and a functional level compared to other common repeats. In functional terms, they are often assumed to be lipid-binding modules that mediate membrane targeting. We addressed this putative activity by focusing on a protein composed solely of MORN repeats-Trypanosoma brucei MORN1. Surprisingly, no evidence for binding to membranes or lipid vesicles by TbMORN1 could be obtained either in vivo or in vitro. Conversely, TbMORN1 did interact with individual phospholipids. High- and low-resolution structures of the MORN1 protein from Trypanosoma brucei and homologous proteins from the parasites Toxoplasma gondii and Plasmodium falciparum were obtained using a combination of macromolecular crystallography, small-angle X-ray scattering, and electron microscopy. This enabled a first structure-based definition of the MORN repeat itself. Furthermore, all three structures dimerised via their C-termini in an antiparallel configuration. The dimers could form extended or V-shaped quaternary structures depending on the presence of specific interface residues. This work provides a new perspective on MORN repeats, showing that they are protein-protein interaction modules capable of mediating both dimerisation and oligomerisation.

BACKGROUND:To increase HIV case finding in a Community-based HIV counselling and testing (CBCT) programme, an index client tracing modality was implemented to target index clients' sexual network and household members. OBJECTIVE:To compare index client tracing modality's outcomes with other CBCT recruitment modalities (mobile, workplace, homebased), 2015-2017. METHODS:Trained HIV counsellors identified HIV positive clients either through offering HIV tests to children and sexual partners of an HIV index client, or randomly offering HIV tests to anyone available in the community (mobile, home-based or workplace). Socio-demographic information and test results were recorded. Descriptive comparisons of client HIV test uptake and positivity were conducted by method of recruitment-index client tracing vs non-targeted community outreach. RESULTS:Of the 1 282 369 people who tested for HIV overall, the index modality tested 3.9% of them, 1.9% in year 1 and 6.0% in year 2. The index modality tested more females than males (55.8% vs 44.2%) overall and in each year; tested higher proportions of children than other modalities: 10.1% vs 2.6% among 1-4 years, 12.2% vs 2.6% among the 5-9 years and 9.6% vs 3.4% among the 10-15 years. The index modality identified higher HIV positivity proportions than other modalities overall (10.3% 95%CI 10.0-10.6 vs. 7.3% 95%CI 7.25-7.36), in year 1 (9.4%; 8.9-9.9 vs 6.5%; 6.45-6.57) and year 2 (10.6%; 10.3-10.9 vs 8.2%; 8.09-8.23). Higher proportions of females (7.5%;7.4-7.5) than males (5.5%;5.4-5.5) tested positive overall. Positivity increased by age up to 49y with year 2's increased targeting of sexual partners. Overall linkage to care rose from 33.3% in year 1 to 78.9% in year 2. CONCLUSIONS:Index testing was less effective in reaching large numbers of clients, but more effective in reaching children and identifying HIV positive people than other modalities. Targeting HIV positive people's partners and children increases HIV case finding.

ObjectiveOur study investigated body image representations in female patients with anorexia nervosa and healthy controls using a size estimation with pictures of their own body. We also explored a method to reduce body image distortions through right hemispheric activation.MethodPictures of participants' own bodies were shown on the left or right visual fields for 130 ms after presentation of neutral, positive, or negative word primes, which could be self-relevant or not, with the task of classifying the picture as "thinner than", "equal to", or "fatter than" one's own body. Subsequently, activation of the left- or right hemispheric through right- or left-hand muscle contractions for 3 min., respectively. Finally, participants completed the size estimation task again.ResultsThe distorted "fatter than" body image was found only in patients and only when a picture of their own body appeared on the right visual field (left hemisphere) and was preceded by negative self-relevant words. This distorted perception of the patients' body image was reduced after left-hand muscle contractions (right hemispheric activation).DiscussionTo reduce body image distortions it is advisable to find methods that help anorexia nervosa patients to increase their self-esteem. The body image distortions were ameliorated after right hemispheric activation. A related method to prevent distorted body-image representations in these patients may be Eye Movement Desensitization and Reprocessing (EMDR) therapy.

IntroductionAlthough current data projects South Africa potentially meeting the UN target to test 90% of all people living with HIV by 2020, linking them to HIV care remains a big challenge. In an effort to increase linkage to care (LTC) of HIV positive clients an innovative collaborative intervention between two non-governmental organisations was developed and implemented between 2016 and 2017. This paper investigated the outcome of this collaborative intervention.MethodsWe used a mixed methods approach to assess the outcome of the innovative relationship. This was done by analysing routine programmatic quantitative data on LTC between 2015 and 2017 and qualitatively interviewing five programme managers, four programme implementers and five HIV positive clients on their perceived success/failure factors. Qualitative data were analysed using thematic content analysis while LTC rates were descriptively analysed. Two consultative meetings presented draft findings to programme managers (n = 7) and implementers (n = 10) for feedback, results verification and confirmation.ResultsIn 2015 cumulative LTC rate was 27% and it rose to 85% two years post-intervention in 2017. Six themes emerged as success factors at the health system and structural levels and these include: provision of client escort services, health facility human resource capacity strengthening, inter and intra-organisational teamwork, onsite LTC, facilitated and expedited jumping of queues and shifting administrative tasks to non-clinical staff to protect nurses' time on ART initiation. These measures in turn ensured increased, affordable and swift ART initiation of clients while strengthening client support.ConclusionsWe concluded that multi-faceted interventions that target both health system challenges including staff shortages, efficiencies, and extended facility opening times, and structural inadequacies, including client time and resource limitations due to poverty or nature of jobs, can help to increase LTC.

[This corrects the article DOI: 10.1371/journal.pone.0116059.].

BackgroundCryptococcal meningitis (CCM) remains a leading cause of mortality amongst HIV infected patients in sub-Saharan Africa. When patients receive recommended therapy, mortality at 10 weeks has been reported to vary between 20 to 36%. However, mortality rate and factors affecting mortality after completing recommended therapy are not well known. We investigated mortality rate, and factors affecting mortality at 2 years among CCM patients following completion of recommended CCM therapy in Uganda.MethodsA retrospective cohort study was conducted among HIV infected patients that had completed 10 weeks of recommended therapy for CCM (2 weeks of intravenous amphotericin B 1mg/kg and 10 weeks of oral Fluconazole 800mg daily) in the CryptoDex trial (ISRCTN59144167) between 2013 and 2015. Survival analysis applying Cox regression was used to determine the mortality rate and factors affecting mortality at 2 years.ResultsThis study followed up 112 participants for 2 years. Mean age (±SD) was 34.9 ± 8, 48 (57.1%) were female and 80 (74.8%) had been on ART for less than 1 year. At 2 years, overall mortality was 30.9% (20 deaths per 100 person-years). Majority of deaths (61.8%) occurred during the first 6 months. In multivariable analysis, mortality was associated with ever being re-admitted since discharge after hospital-based management of CCM (aHR = 13.33, 95% CI: 5.92-30.03), p75% compared to ConclusionThere remains a considerable risk of mortality in the first two years after completion of standard therapy for CCM in resource-limited settings with risk highest during the first 6 months. Maintenance of patient follow up during this period may reduce mortality.

Leptospirosis is a zoonotic bacterial disease that affects more than one million people worldwide each year. Human infection is acquired through direct or indirect contact with the urine of an infected animal. A wide range of animals including rodents and livestock may shed Leptospira bacteria and act as a source of infection for people. In the Kilimanjaro Region of northern Tanzania, leptospirosis is an important cause of acute febrile illness, yet relatively little is known about animal hosts of Leptospira infection in this area. The roles of rodents and ruminant livestock in the epidemiology of leptospirosis were evaluated through two linked studies. A cross-sectional study of peri-domestic rodents performed in two districts with a high reported incidence of human leptospirosis found no evidence of Leptospira infection among rodent species trapped in and around randomly selected households. In contrast, pathogenic Leptospira infection was detected in 7.08% cattle (n = 452 [5.1-9.8%]), 1.20% goats (n = 167 [0.3-4.3%]) and 1.12% sheep (n = 89 [0.1-60.0%]) sampled in local slaughterhouses. Four Leptospira genotypes were detected in livestock. Two distinct clades of L. borgpetersenii were identified in cattle as well as a clade of novel secY sequences that showed only 95% identity to known Leptospira sequences. Identical L. kirschneri sequences were obtained from qPCR-positive kidney samples from cattle, sheep and goats. These results indicate that ruminant livestock are important hosts of Leptospira in northern Tanzania. Infected livestock may act as a source of Leptospira infection for people. Additional work is needed to understand the role of livestock in the maintenance and transmission of Leptospira infection in this region and to examine linkages between human and livestock infections.

Work craving theory addresses how work-addicted individuals direct great emotion-regulatory efforts to weave their addictive web of working. They crave work for two main emotional incentives: to overcompensate low self-worth and to escape (i.e., reduce) negative affect, which is strategically achieved through neurotic perfectionism and compulsive working. Work-addicted individuals' strong persistence and self-discipline with respect to work-related activities suggest strong skills in volitional action control. However, their inability to disconnect from work implies low volitional skills. How can work-addicted individuals have poor and strong volitional skills at the same time? To answer this paradox, we elaborated on the relevance of two different volitional modes in work craving: self-regulation (self-maintenance) and self-control (goal maintenance). Four hypotheses were derived from Wojdylo's work craving theory and Kuhl's self-regulation theory: (H1) Work craving is associated with a combination of low self-regulation and high self-control. (H2) Work craving is associated with symptoms of psychological distress. (H3) Low self-regulation is associated with psychological distress symptoms. (H4) Work craving mediates the relationships between self-regulation deficits and psychological distress symptoms at high levels of self-control. Additionally, we aimed at supporting the discriminant validity of work craving with respect to work engagement by showing their different volitional underpinnings. Results of the two studies confirmed our hypotheses: whereas work craving was predicted by high self-control and low self-regulation and associated with higher psychological distress, work engagement was predicted by high self-regulation and high self-control and associated with lower symptoms of psychological distress. Furthermore, work styles mediated the relationship between volitional skills and symptoms of psychological distress. Based on these new insights, several suggestions for prevention and therapeutic interventions for work-addicted individuals are proposed.

Reaching movements are comprised of the coordinated action across multiple joints. The human skeleton is redundant for this task because different joint configurations can lead to the same endpoint in space. How do people learn to use combinations of joints that maximize success in goal-directed motor tasks? To answer this question, we used a 3-degree-of-freedom manipulandum to measure shoulder, elbow and wrist joint movements during reaching in a plane. We tested whether a shift in the relative contribution of the wrist and elbow joints to a reaching movement could be learned by an implicit reinforcement regime. Unknown to the participants, we decreased the task success for certain joint configurations (wrist flexion or extension, respectively) by adding random variability to the endpoint feedback. In return, the opposite wrist postures were rewarded in the two experimental groups (flexion and extension group). We found that the joint configuration slowly shifted towards movements that provided more control over the endpoint and hence higher task success. While the overall learning was significant, only the group that was guided to extend the wrist joint more during the movement showed substantial learning. Importantly, all changes in movement pattern occurred independent of conscious awareness of the experimental manipulation. These findings suggest that the motor system is generally sensitive to its output variability and can optimize joint-space solutions that minimize task-relevant output variability. We discuss biomechanical biases (e.g. joint's range of movement) that could impose hurdles to the learning process.

BACKGROUND:Pediatric hospital mortality from infectious diseases in resource constrained countries remains unacceptably high. Improved methods of risk-stratification can assist in referral decision making and resource allocation. The purpose of this study was to create prediction models for in-hospital mortality among children admitted with suspected infectious diseases. METHODS:This two-site prospective observational study enrolled children between 6 months and 5 years admitted with a proven or suspected infection. Baseline clinical and laboratory variables were collected on enrolled children. The primary outcome was death during admission. Stepwise logistic regression minimizing Akaike's information criterion was used to identify the most promising multivariate models. The final model was chosen based on parsimony. RESULTS:1307 children were enrolled consecutively, and 65 (5%) of whom died during their admission. Malaria, pneumonia and gastroenteritis were diagnosed in 50%, 31% and 8% of children, respectively. The primary model included an abnormal Blantyre coma scale, HIV and weight-for-age z-score. This model had an area under the curve (AUC) of 0.85 (95% CI, 0.80-0.89) with a sensitivity and specificity of 83% and 76%, respectively. The positive and negative predictive values were 15% and 99%, respectively. Two alternate models with similar performance characteristics were developed withholding HIV and weight-for-age z-score, for use when these variables are not available. CONCLUSIONS:Risk stratification of children admitted with infectious diseases can be calculated based on several easily measured variables. Risk stratification at admission can be used for allocation of scarce human and physical resources and to guide referral among children admitted to lower level health facilities.

This study is the first to partially quantify the potential economic benefits that a vaccine, effective at protecting cattle against malignant catarrhal fever (MCF), could accrue to pastoralists living in East Africa. The benefits would result from the removal of household resource and management costs that are traditionally incurred avoiding the disease. MCF, a fatal disease of cattle caused by a virus transmitted from wildebeest calves, has plagued Maasai communities in East Africa for generations. The threat of the disease forces the Maasai to move cattle to less productive grazing areas to avoid wildebeest during calving season when forage quality is critical. To assess the management and resource costs associated with moving, we used household survey data. To estimate the costs associated with changes in livestock body condition that result from being herded away from wildebeest calving grounds, we exploited an ongoing MCF vaccine field trial and we used a hedonic price regression, a statistical model that allows estimation of the marginal contribution of a good's attributes to its market price. We found that 90 percent of households move, on average, 82 percent of all cattle away from home to avoid MCF. In doing so, a herd's productive contributions to the household was reduced, with 64 percent of milk being unavailable for sale or consumption by the family members remaining at the boma (the children, women, and the elderly). In contrast cattle that remained on the wildebeest calving grounds during the calving season (and survived MCF) remained fully productive to the family and gained body condition compared to cattle that moved away. This gain was, however, short-lived. We estimated the market value of these condition gains and losses using hedonic regression. The value of a vaccine for MCF is the removal of the costs incurred in avoiding the disease.

Alcelaphine herpesvirus-1 (AlHV-1), a causative agent of malignant catarrhal fever in cattle, was detected in wildebeest (Connochaetes taurinus) placenta tissue for the first time. Although viral load was low, the finding of viral DNA in over 50% of 94 samples tested lends support to the possibility that placental tissue could play a role in disease transmission and that wildebeest calves are infected in utero. Two viral loci were sequenced to examine variation among virus samples obtained from wildebeest and cattle: the ORF50 gene, encoding the lytic cycle transactivator protein, and the A9.5 gene, encoding a novel polymorphic viral glycoprotein. ORF50 was well conserved with six newly discovered alleles differing at only one or two base positions. In contrast, while only three new A9.5 alleles were discovered, these differed by up to 13% at the nucleotide level and up to 20% at the amino acid level. Structural homology searching performed with the additional A9.5 sequences determined in this study adds power to recent analysis identifying the four-helix bundle cytokine interleukin-4 (IL4) as the major homologue. The majority of MCF virus samples obtained from Tanzanian cattle and wildebeest encoded A9.5 polypeptides identical to the previously characterized A9.5 allele present in the laboratory maintained AlHV-1 C500 strain. This supports the view that AlHV-1 C500 is suitable for the development of a vaccine for wildebeest-associated MCF.

One strategy in cancer immunotherapy is to capitalize on the key immunoregulatory and antigen presenting capabilities of dendritic cells (DCs). This approach is dependent on efficient delivery of tumor specific antigens to DCs, which subsequently induce an anti-tumor T-cell mediated immune response. Human adenovirus serotype 5 (HAdV5) has been used in human studies for gene delivery, but has limited infection in DCs, which lack the proper receptors. Addition of the porcine fiber knob (PK) from porcine adenovirus type 4 to HAdV5 allows the virus to deliver genetic material via binding to glycosylated surface proteins and bypasses the coxsackie-and-adenovirus receptor required by wild-type HAdV5. In this study we explored the potential therapeutic applications of an adenovirus with PK-based tropism against cancers expressing mesothelin. Infectivity and gene transfer assays were used to compare Ad5-PK to wild-type HAdV5. Mouse models were used to demonstrate peptide specificity and T-cell responses. We show that the PK modification highly augmented infection of DCs, including the CD141+ DC subset, a key subset for activation of naïve CD8+ T-cells. We also show that Ad5-PK increases DC infectivity and tumor specific antigen expression. Finally, vaccination of mice with the Ad5-PK vector resulted in enhanced T-cell-mediated interferon gamma (IFN-γ) release in response to both mesothelin peptide and a tumor line expressing mesothelin. Ad5-PK is a promising tool for cancer immunotherapy as it improves infectivity, gene transfer, protein expression, and subsequent T-cell activation in DCs compared to wild-type HAdV5 viruses.

Disclosure of the diagnosis of HIV to HIV-infected children is challenging for caregivers. Despite current recommendations, data suggest that levels of disclosure of HIV status to HIV-infected children receiving care in resource-limited settings are very low. Few studies describe the disclosure process for children in these settings, particularly the motivators, antecedent goals, and immediate outcomes of disclosure to HIV-infected children. This study examined caregivers' perception of the disclosure concept prior to disclosure, their motivation towards or away from disclosure, and their short- and long-term intentions for disclosure to their HIV-infected children.In-depth interviews were conducted with primary caregivers of 40 HIV-infected children (ages 5-15 years) who were receiving HIV care but did not know their HIV status.Caregivers of HIV-infected children mainly perceived disclosure as a single event rather than a process of gradual delivery of information about the child's illness. They viewed disclosure as potentially beneficial both to children and themselves, as well as an opportunity to explain the parents' role in the transmission of HIV to the children. Caregivers desired to personally conduct the disclosure; however, most reported being over-whelmed with fear of negative outcomes and revealed a lack of self-efficacy towards managing the disclosure process. Consequently, most cope by deception to avoid or delay disclosure until they perceive their own readiness to disclose.Interventions for HIV disclosure should consider that caregivers may desire to be directly responsible for disclosure to children under their care. They, however, need to be empowered with practical skills to recognize opportunities to initiate the disclosure process early, as well as supported to manage it in a phased, developmentally appropriate manner. The potential role for peer counselors in the disclosure process deserves further study.

The aim of this study was to determine the impact of the domestic care environment on the prevalence of potentially traumatic events (PTEs) and posttraumatic stress disorder (PTSD) among orphaned and separated children in Uasin Gishu County, western Kenya.A total of 1565 (55.5% male) orphaned and separated adolescents aged 10-18 years (mean 13.8 years, sd 2.2), were assessed for PTSD and PTEs including bullying, physical abuse and sexual abuse. In this sample, 746 lived in extended family households, 746 in Charitable Children's Institutions (CCIs), and 73 on the street. Posttraumatic stress symptom (PTSS) scores and PTSD were assessed using the Child PTSD Checklist.Bullying was the commonest PTE in all domestic care environments, followed by physical and sexual abuse. All PTEs were commonest among the street youth followed by CCIs. However, sexual abuse was more prevalent in households than in CCIs. Prevalence of PTSD was highest among street youth (28.8%), then households (15.0%) and CCIs (11.5%). PTSS scores were also highest among street youth, followed by CCIs and households. Bullying was associated with higher PTSS scores and PTSD odds than either sexual or physical abuse.This study demonstrated differences in distribution of trauma and PTSD among orphaned and separated children in different domestic care environments, with street youth suffering more than those in CCIs or households. Interventions are needed to address bullying and sexual abuse, especially in extended family households. Street youth, a heretofore neglected population, are urgently in need of dedicated mental health services and support.

Street-connected youth are a neglected and vulnerable population, particularly in resource-constrained settings. The development of interventions and supports for this population requires insight into how they live. This study describes the social and economic characteristics of a convenience sample of street youth (SY) in Eldoret, Kenya.Participants were eligible if they were aged 12-21, living in Eldoret, spending days only (part-time), or nights and days on the street (full-time) and able and willing to consent or assent. Data were collected using a standardized interview conducted in English or Kiswahili. Binary dependent variables were having been arrested and/or jailed, and first priority for spending money (food vs. other). Nominal categorical dependent variables included major source of support, and major reason for being street-involved. Multivariable analysis used logistic regression models to examine the association of gender and level of street-involvement with social and economic factors of interest adjusting for age and length of time on the street. Data were analyzed using SAS 9.3.Of the 200 SY enrolled, 41% were female, mean age of 16.3 years; 71% were on the street full-time, and 29% part-time. Compared with part-time SY, full-time SY were more likely to have been arrested (Adjusted Odds Ratio [AOR]: 2.33, 95% Confidence Interval [95%CI]:1.01-5.35), name food as their first spending priority (AOR: 2.57, 95%CI:1.03-6.45), have left home due to violence (AOR: 5.54, 95%CI: 1.67-18.34), and more likely to report friends on the street as a major source of support (AOR: 3.59, 95% CI: 1.01-12.82). Compared with females, males were more likely to have ever been arrested (AOR: 2.66, 95%CI:1.14-6.18), and to have ever been jailed (AOR: 3.22, 95%CI:1.47-7.02).These results suggest a high degree of heterogeneity and vulnerability among SY in this setting. There is an urgent need for interventions taking into consideration these characteristics.

To describe the nutritional status of orphaned and separated children and adolescents (OSCA) living in households in the community (HH), on the street, and those in institutional environments in western Kenya.The study enrolled OSCA from 300 randomly selected households (HH), 19 Charitable Children's Institutions (CCIs), and 100 street-involved children. Measures of malnutrition were standardized with Z-scores using World Health Organization criteria; Z-scores ≤-2 standard deviations (sd) were moderate-severe malnutrition. Data were analyzed using multivariable logistic regression adjusting for child age, sex, HIV status, whether the child had been hospitalized in the previous year, time living with current guardian, and intra-household clustering for adequacy of diet and moderate-severe malnutrition.Included are data from 2862 participants (1337 in CCI's, 1425 in HH's, and 100 street youth). The population was 46% female with median age at enrolment of 11.1 years. Only 4.4% of households and institutions reported household food security; 93% of children in HH reported an adequate diet vs. 95% in CCI's and 99% among street youth. After adjustment, OSCA in HH were less likely to have an adequate diet compared to those in CCI's (AOR 0.4, 95% CI 0.2-1.0). After adjustment, there were no differences between the categories of children on weight-for-age, weight-for-height, or BMI-for-age. Children living in HH (AOR 2.6, 95% CI: 2.0-3.4) and street youth (AOR: 5.9, 95% CI: 3.6-9.5) were more likely than children in CCI's to be low height-for-age.OSCA in HH are less likely to have an adequate diet compared to children in CCI's. They and street children are more likely to be moderately-severely low height-for-age compared to children in CCI's, suggesting chronic malnutrition among them.

Neonatal sepsis in the developing world is incompletely characterized. We seek to characterize the microbial spectrum involved in sepsis and determine the role of maternal transmission by comparing organisms that can be cultured from septic newborn infants and their mothers. From 80 consecutive mother-infant pairs meeting clinical criteria for neonatal sepsis, we collected infant blood and spinal fluid, and maternal blood and vaginal specimens. Identifiable bacteria were recovered from the blood in 32.5% of infants, and from 2.5% of cerebrospinal fluid cultures, for a total of 35% recoverable putative causative agents. Bacteria recovered from vaginal specimens were not concordant with those recovered from infants. Similarly there was no concordance of bacteria recovered from blood and cerebrospinal fluid. We conclude that relying on traditional bacterial culture techniques does not adequately delineate the role of maternal versus environmental sources of neonatal sepsis in this setting. More sensitive molecular approaches will be needed to properly characterize the maternal and environmental microbial community involved in neonatal sepsis in such developing countries.

Adherence to HIV antiretroviral therapy (ART) among children in developing settings is poorly understood.To understand the level, distribution, and correlates of ART adherence behavior, we prospectively determined monthly ART adherence through multiple measures and six-monthly HIV RNA levels among 121 Ugandan children aged 2-10 years for one year. Median adherence levels were 100% by three-day recall, 97.4% by 30-day visual analog scale, 97.3% by unannounced pill count/liquid formulation weights, and 96.3% by medication event monitors (MEMS). Interruptions in MEMS adherence of ≥ 48 hours were seen in 57.0% of children; 36.3% had detectable HIV RNA at one year. Only MEMS correlated significantly with HIV RNA levels (r = -0.25, p = 0.04). Multivariable regression found the following to be associated with

BackgroundThe Internet is fast gaining recognition as a powerful, low-cost method to deliver health intervention and prevention programs to large numbers of young people across diverse geographic regions. The feasibility and accessibility of Internet-based health interventions in resource-limited settings, where cost-effective interventions are most needed, is unknown. To determine the utility of developing technology-based interventions in resource-limited settings, availability and patterns of usage of the Internet first need to be assessed.Methods and findingsThe Uganda Media and You Survey was a cross-sectional survey of Internet use among adolescents (ages 12-18 years) in Mbarara, Uganda, a municipality mainly serving a rural population in sub-Saharan Africa. Participants were randomly selected among eligible students attending one of five participating secondary day and boarding schools in Mbarara, Uganda. Of a total of 538 students selected, 93% (500) participated. Of the total respondents, 45% (223) reported ever having used the Internet, 78% (175) of whom reported going online in the previous week. As maternal education increased, so too did the odds of adolescent Internet use. Almost two in five respondents (38% [189]) reported already having used a computer or the Internet to search for health information. Over one-third (35% [173]) had used the computer or Internet to find information about HIV/AIDS, and 20% (102) had looked for sexual health information. Among Internet users, searching for HIV/AIDS information on a computer or online was significantly related to using the Internet weekly, emailing, visiting chat rooms, and playing online games. In contrast, going online at school was inversely related to looking for HIV/AIDS information via technology. If Internet access were free, 66% (330) reported that they would search for information about HIV/AIDS prevention online.ConclusionsBoth the desire to use, and the actual use of, the Internet to seek sexual health and HIV/AIDS information is high among secondary school students in Mbarara. The Internet may be a promising strategy to deliver low-cost HIV/AIDS risk reduction interventions in resource-limited settings with expanding Internet access.