Measuring fitness of Kenyan children with polyparasitic infections using the 20-meter shuttle run test as a morbidity metric.

BACKGROUND: To date, there has been no standardized approach to the assessment of aerobic fitness among children who harbor parasites. In quantifying the disability associated with individual or multiple chronic infections, accurate measures of physical fitness are important metrics. This is because exercise intolerance, as seen with anemia and many other chronic disorders, reflects the body's inability to maintain adequate oxygen supply (VO(2) max) to the motor tissues, which is frequently linked to reduced quality-of-life in terms of physical and job performance. The objective of our study was to examine the associations between polyparasitism, anemia, and reduced fitness in a high risk Kenyan population using novel implementation of the 20-meter shuttle run test (20mSRT), a well-standardized, low-technology physical fitness test. METHODOLOGY/PRINCIPAL FINDINGS: Four villages in coastal Kenya were surveyed during 2009-2010. Children 5-18 years were tested for infection with Schistosoma haematobium (Sh), malaria, filaria, and geohelminth infections by standard methods. After anthropometric and hemoglobin testing, fitness was assessed with the 20 mSRT. The 20 mSRT proved easy to perform, requiring only minimal staff training. Parasitology revealed high prevalence of single and multiple parasitic infections in all villages, with Sh being the most common (25-62%). Anemia prevalence was 45-58%. Using multiply-adjusted linear modeling that accounted for household clustering, decreased aerobic capacity was significantly associated with anemia, stunting, and wasting, with some gender differences. CONCLUSIONS/SIGNIFICANCE: The 20 mSRT, which has excellent correlation with VO(2), is a highly feasible fitness test for low-resource settings. Our results indicate impaired fitness is common in areas endemic for parasites, where, at least in part, low fitness scores are likely to result from anemia and stunting associated with chronic infection. The 20 mSRT should be used as a common metric to quantify physical fitness and compare sub-clinical disability across many different disorders and community settings

T-Branes and Monodromy

We introduce T-branes, or "triangular branes," which are novel non-abelian bound states of branes characterized by the condition that on some loci, their matrix of normal deformations, or Higgs field, is upper triangular. These configurations refine the notion of monodromic branes which have recently played a key role in F-theory phenomenology. We show how localized matter living on complex codimension one subspaces emerge, and explain how to compute their Yukawa couplings, which are localized in complex codimension two. Not only do T-branes clarify what is meant by brane monodromy, they also open up a vast array of new possibilities both for phenomenological constructions and for purely theoretical applications. We show that for a general T-brane, the eigenvalues of the Higgs field can fail to capture the spectrum of localized modes. In particular, this provides a method for evading some constraints on F-theory GUTs which have assumed that the spectral equation for the Higgs field completely determines a local model.Comment: 110 pages, 5 figure

Characterization of drug-induced human mitochondrial ADP/ATP carrier inhibition.

An increasing number of commonly prescribed drugs are known to interfere with mitochondrial function, causing cellular toxicity, but the underlying mechanisms are largely unknown. Although often not considered, mitochondrial transport proteins form a significant class of potential mitochondrial off-targets. So far, most drug interactions have been reported for the mitochondrial ADP/ATP carrier (AAC), which exchanges cytosolic ADP for mitochondrial ATP. Here, we show inhibition of cellular respiratory capacity by only a subset of the 18 published AAC inhibitors, which questions whether all compound do indeed inhibit such a central metabolic process. This could be explained by the lack of a simple, direct model system to evaluate and compare drug-induced AAC inhibition. Methods: For its development, we have expressed and purified human AAC1 (hAAC1) and applied two approaches. In the first, thermostability shift assays were carried out to investigate the binding of these compounds to human AAC1. In the second, the effect of these compounds on transport was assessed in proteoliposomes with reconstituted human AAC1, enabling characterization of their inhibition kinetics. Results: Of the proposed inhibitors, chebulinic acid, CD-437 and suramin are the most potent with IC50-values in the low micromolar range, whereas another six are effective at a concentration of 100 μM. Remarkably, half of all previously published AAC inhibitors do not show significant inhibition in our assays, indicating that they are false positives. Finally, we show that inhibitor strength correlates with a negatively charged surface area of the inhibitor, matching the positively charged surface of the substrate binding site. Conclusion: Consequently, we have provided a straightforward model system to investigate AAC inhibition and have gained new insights into the chemical compound features important for inhibition. Better evaluation methods of drug-induced inhibition of mitochondrial transport proteins will contribute to the development of drugs with an enhanced safety profile

Centipede venoms as a source of drug leads

peerreview_statement: The publishing and review policy for this title is described in its Aims & Scope. aims_and_scope_url: http://www.tandfonline.com/action/journalInformation?show=aimsScope&journalCode=iedc20© 2016 Taylor and Francis. The attached document is the authors' final submitted version of the journal article. You are advised to consult the publisher's version if you wish to cite from it

Evaluation of the health-related quality of life of children in Schistosoma haematobium-endemic communities in Kenya: a cross-sectional study.

BACKGROUND: Schistosomiasis remains a global public health challenge, with 93% of the ~237 million infections occurring in sub-Saharan Africa. Though rarely fatal, its recurring nature makes it a lifetime disorder with significant chronic health burdens. Much of its negative health impact is due to non-specific conditions such as anemia, undernutrition, pain, exercise intolerance, poor school performance, and decreased work capacity. This makes it difficult to estimate the disease burden specific to schistosomiasis using the standard DALY metric. METHODOLOGY/PRINCIPAL FINDINGS: In our study, we used Pediatric Quality of Life Inventory (PedsQL), a modular instrument available for ages 2-18 years, to assess health-related quality of life (HrQoL) among children living in a Schistosoma haematobium-endemic area in coastal Kenya. The PedsQL questionnaires were administered by interview to children aged 5-18 years (and their parents) in five villages spread across three districts. HrQoL (total score) was significantly lower in villages with high prevalence of S. haematobium (-4.0%, p<0.001) and among the lower socioeconomic quartiles (-2.0%, p<0.05). A greater effect was seen in the psychosocial scales as compared to the physical function scale. In moderate prevalence villages, detection of any parasite eggs in the urine was associated with a significant 2.1% (p<0.05) reduction in total score. The PedsQL reliabilities were generally high (Cronbach alphas ≥0.70), floor effects were acceptable, and identification of children from low socioeconomic standing was valid. CONCLUSIONS/SIGNIFICANCE: We conclude that exposure to urogenital schistosomiasis is associated with a 2-4% reduction in HrQoL. Further research is warranted to determine the reproducibility and responsiveness properties of QoL testing in relation to schistosomiasis. We anticipate that a case definition based on more sensitive parasitological diagnosis among younger children will better define the immediate and long-term HrQoL impact of Schistosoma infection

On Global Flipped SU(5) GUTs in F-theory

We construct an SU(4) spectral divisor and its factorization of types (3,1) and (2,2) based on the construction proposed in [1]. We calculate the chiral spectra of flipped SU(5) GUTs by using the spectral divisor construction. The results agree with those from the analysis of semi-local spectral covers. Our computations provide an example for the validity of the spectral divisor construction and suggest that the standard heterotic formulae are applicable to the case of F-theory on an elliptically fibered Calabi-Yau fourfold with no heterotic dual.Comment: 45 pages, 12 tables, 1 figure; typos corrected, footnotes added, and a reference adde

Audit of head injury management in Accident and Emergency at two hospitals: implications for NICE CT guidelines

BACKGROUND: The National Institute for Clinical Excellence (NICE) has produced guidelines on the early management of head injury. This study audits the process of the management of patients with head injury presenting at Accident and Emergency (A&E) departments and examines the impact upon resources of introducing NICE guidelines for eligibility of a CT scan. METHODS: A retrospective audit of consecutive patients of any age, presenting at A&E with a complaint of head injury during one month in two northern District General Hospitals forming part of a single NHS Trust. RESULTS: 419 patients presented with a median age of 15.5 years, and 61% were male. 58% had a Glasgow Coma Score (GCS) recorded and 33 (8%) were admitted. Only four of the ten indicators for a CT scan were routinely assessed, but data were complete for only one (age), and largely absent for another (vomiting). Using just three (incomplete) indicators showed a likely 4 fold increase in the need for a CT scan. CONCLUSIONS: The majority of patients who present with a head injury to Accident and Emergency departments are discharged home. Current assessment processes and associated data collection routines do not provide the information necessary to implement NICE guidelines for CT brain scans. The development of such clinical audit systems in a busy A&E department is likely to require considerable investment in technology and/or staff. The resource implications for radiology are likely to be substantial

Flipped SU(5) GUTs from E_8 Singularities in F-theory

In this paper we construct supersymmetric flipped SU(5) GUTs from E_8 singularities in F-theory. We start from an SO(10) singularity unfolded from an E_8 singularity by using an SU(4) spectral cover. To obtain realistic models, we consider (3,1) and (2,2) factorizations of the SU(4) cover. After turning on the massless U(1)_X gauge flux, we obtain the SU(5) X U(1)_X gauge group. Based on the well-studied geometric backgrounds in the literature, we demonstrate several models and discuss their phenomenology.Comment: 46 pages, 23 tables, 1 figure, typos corrected, references added, and new examples presente

Patellar and hamstring autografts are associated with different jump task loading asymmetries after ACL reconstruction

© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd After anterior cruciate ligament reconstruction (ACLR), there is a higher re-injury rate to the contralateral limb in athletes who undergo surgery using a bone-patellar-tendon-bone (BPTB) autograft than using a semitendinosus and gracilis hamstring tendon (HT) autograft. This may be influenced by differing lower-limb loading asymmetries present when athletes of each graft type return to play (RTP). The aim of this study was to compare bilateral countermovement jump (CMJ) phase-specific impulse asymmetries between athletes with BPTB and HT autografts 9 months post-ACLR, and to identify the relationship between impulse and isokinetic strength asymmetries. Male field sport athletes with a BPTB (n = 22) or HT (n = 22) autograft were tested approximately 9 months post-ACLR. An uninjured control group (n = 22) was also tested on a single occasion. Phase-specific bilateral absolute impulse asymmetries were calculated during the CMJ and compared between groups using Kruskal-Wallis and post-hoc testing. A linear regression model was used to assess the relationship between impulse asymmetries and isokinetic concentric knee extensor strength asymmetries. BPTB athletes demonstrated greater impulse asymmetries than HT athletes during the eccentric (P = 0.01) and concentric (P = 0.008) phases of the jump. Isokinetic strength asymmetry was a significant predictor of CMJ concentric impulse asymmetry in both BPTB (r2 = 0.39) and HT athletes (r2 = 0.18) but not eccentric impulse asymmetry in any group. The greater loading asymmetries demonstrated by BPTB than HT athletes 9 months after ACLR may contribute to the differing incidence rates of contralateral ACL injury. The findings suggest that graft-specific loading asymmetries should be targeted during rehabilitation prior to RTP