A prospective study of mortality from cryptococcal meningitis following treatment induction with 1200 mg oral fluconazole in Blantyre, Malawi.

OBJECTIVE: We have previously reported high ten-week mortality from cryptococcal meningitis in Malawian adults following treatment-induction with 800 mg oral fluconazole (57% [33/58]). National guidelines in Malawi and other African countries now advocate an increased induction dose of 1200 mg. We assessed whether this has improved outcomes. DESIGN: This was a prospective observational study of HIV-infected adults with cryptococcal meningitis confirmed by diagnostic lumbar puncture. Treatment was with fluconazole 1200 mg/day for two weeks then 400mg/day for 8 weeks. Mortality within the first 10 weeks was the study end-point, and current results were compared with data from our prior patient cohort who started on fluconazole 800 mg/day. RESULTS: 47 participants received fluconazole monotherapy. Despite a treatment-induction dose of 1200 mg, ten-week mortality remained 55% (26/47). This was no better than our previous study (Hazard Ratio [HR] of death on 1200 mg vs. 800 mg fluconazole: 1.29 (95% CI: 0.77-2.16, p = 0.332)). There was some evidence for improved survival in patients who had repeat lumbar punctures during early therapy to lower intracranial pressure (HR: 0.27 [95% CI: 0.07-1.03, p = 0.055]). CONCLUSION: There remains an urgent need to identify more effective, affordable and deliverable regimens for cryptococcal meningitis

The mechanical and electrical properties of direct-spun carbon nanotube mats

The mechanical and electrical properties of a direct-spun carbon nanotube mat are measured. The mat comprises an interlinked random network of nanotube bundles, with approximately 40 nanotubes in a bundle. A small degree of in-plane anisotropy is observed. The bundles occasionally branch, and the mesh topology resembles a 2D lattice of nodal connectivity slightly below 4. The macroscopic in-plane tensile response is elasto-plastic in nature, with significant orientation hardening. In-situ microscopy reveals that the nanotube bundles do not slide past each other at their junctions under macroscopic stain. A micromechanical model is developed to relate the macroscopic modulus and flow strength to the longitudinal shear response of the nanotube bundles. The mechanical and electrical properties of the mat are compared with those of other nanotube arrangements over a wide range of density

Some algorithms to solve a bi-objectives problem for team selection

In real life, many problems are instances of combinatorial optimization. Cross-functional team selection is one of the typical issues. The decision-maker has to select solutions among (kh) solutions in the decision space, where k is the number of all candidates, and h is the number of members in the selected team. This paper is our continuing work since 2018; here, we introduce the completed version of the Min Distance to the Boundary model (MDSB) that allows access to both the "deep" and "wide" aspects of the selected team. The compromise programming approach enables decision-makers to ignore the parameters in the decision-making process. Instead, they point to the one scenario they expect. The aim of model construction focuses on finding the solution that matched the most to the expectation. We develop two algorithms: one is the genetic algorithm and another based on the philosophy of DC programming (DC) and its algorithm (DCA) to find the optimal solution. We also compared the introduced algorithms with the MIQP-CPLEX search algorithm to show their effectiveness

Do the global lung function initiative reference equations reflect a sample of adult Middle Eastern population?

Introduction The Global Lung Function Initiative (GLI) 2012 introduced new multi-ethnic spirometry reference values for numerous ethnicities. Objectives The aim of this study was to investigate the suitability of the GLI reference values for the adult Jordanian population. Methods: 1875 (1029 females and 846 males) healthy non-smoking adults were enrolled from several locations in Jordan. Spirometry tests were performed. Z scores and predicted normal values were calculated for each participant using GLI 2012 equations in addition to other local equations from the Middle East. Results Our results indicated that none of the GLI 2012 or other regional equations studied produced an acceptable fit to our data. Conclusion A need to formulate a specific equation for the Jordanian population is urgently required to better evaluate their respiratory conditions. Keywords

Effect of gamified perceptual learning on visual detection and discrimination skills in equine gait assessment

Background Visual assessment of equine lameness is an everyday veterinary task suffering from poor diagnostic accuracy. The aim of this study was to quantify the impact of the perceptual learning game ‘LamenessTrainer’ on skill development. Methods Thirty‐six undergraduate veterinary students engaged in four game modules teaching the assessment of fore‐ and hindlimb lameness. Computer animations of horses in this game displayed 0% (sound) to 70% (moderately lame) vertical movement asymmetry of head and pelvis. Performance, learning effects, diagnostic accuracy, detection thresholds and survey responses were analysed. Results Following staircase learning, more than 80% of students reliably classified horses with ≥20% asymmetry for forelimb lameness, ≥40% asymmetry for simplified hindlimb lameness and ≥50% asymmetry for realistic hindlimb lameness. During random presentation, on average 82% of sound and 65% of lame horses were assessed correctly during forelimb lameness evaluation, dropping to 39% of sound and 56% of lame horses for hindlimb lameness. Conclusion In less than two hours, systematic perceptual learning through deliberate practice can develop visual assessment skills to an accuracy level comparable to expert assessors scoring the same animations. Skills should be developed further to improve misclassifications of sound and mildly lame horses, especially for hindlimb lameness evaluation

Prior Pulmonary Tuberculosis Is a Risk Factor for Asymptomatic Cryptococcal Antigenemia in a Cohort of Adults With Advanced Human Immunodeficiency Virus Disease.

The greater mortality risk among people with advanced human immunodeficiency virus disease and cryptococcal antigenemia, despite treatment, indicates an increased susceptibility to other infections. We found that prior tuberculosis was an independent risk factor for cryptococcal antigenemia (adjusted odds ratio, 2.72; 95% confidence interval, 1.13-6.52; P = .03) among patients with CD4 counts <100 cells/µL

Cell migration leads to spatially distinct but clonally related airway cancer precursors

Background Squamous cell carcinoma of the lung is a common cancer with 95% mortality at 5 years. These cancers arise from preinvasive lesions, which have a natural history of development progressing through increasing severity of dysplasia to carcinoma in situ (CIS), and in some cases, ending in transformation to invasive carcinoma. Synchronous preinvasive lesions identified at autopsy have been previously shown to be clonally related. Methods Using autofluorescence bronchoscopy that allows visual observation of preinvasive lesions within the upper airways, together with molecular profiling of biopsies using gene sequencing and loss-of-heterozygosity analysis from both preinvasive lesions and from intervening normal tissue, we have monitored individual lesions longitudinally and documented their visual, histological and molecular relationship. Results We demonstrate that rather than forming a contiguous field of abnormal tissue, clonal CIS lesions can develop at multiple anatomically discrete sites over time. Further, we demonstrate that patients with CIS in the trachea have invariably had previous lesions that have migrated proximally, and in one case, into the other lung over a period of 12 years. Conclusions Molecular information from these unique biopsies provides for the first time evidence that field cancerisation of the upper airways can occur through cell migration rather than via local contiguous cellular expansion as previously thought. Our findings urge a clinical strategy of ablating high-grade premalignant airway lesions with subsequent attentive surveillance for recurrence in the bronchial tree

A Characterization of Scale Invariant Responses in Enzymatic Networks

An ubiquitous property of biological sensory systems is adaptation: a step increase in stimulus triggers an initial change in a biochemical or physiological response, followed by a more gradual relaxation toward a basal, pre-stimulus level. Adaptation helps maintain essential variables within acceptable bounds and allows organisms to readjust themselves to an optimum and non-saturating sensitivity range when faced with a prolonged change in their environment. Recently, it was shown theoretically and experimentally that many adapting systems, both at the organism and single-cell level, enjoy a remarkable additional feature: scale invariance, meaning that the initial, transient behavior remains (approximately) the same even when the background signal level is scaled. In this work, we set out to investigate under what conditions a broadly used model of biochemical enzymatic networks will exhibit scale-invariant behavior. An exhaustive computational study led us to discover a new property of surprising simplicity and generality, uniform linearizations with fast output (ULFO), whose validity we show is both necessary and sufficient for scale invariance of enzymatic networks. Based on this study, we go on to develop a mathematical explanation of how ULFO results in scale invariance. Our work provides a surprisingly consistent, simple, and general framework for understanding this phenomenon, and results in concrete experimental predictions

Middle Pleistocene vertebrate fossils from the Nefud Desert, Saudi Arabia: Implications for biogeography and palaeoecology

The current paucity of Pleistocene vertebrate records from the Arabian Peninsula - a landmass of over 3 million km2 - is a significant gap in our knowledge of the Quaternary. Such data are critical lines of contextual evidence for considering animal and hominin dispersals between Africa and Eurasia generally, and hominin palaeoecology in the Pleistocene landscapes of the Arabian interior specifically. Here, we describe an important contribution to the record and report stratigraphically-constrained fossils of mammals, birds and reptiles from recent excavations at Ti’s al Ghadah in the southwestern Nefud Desert. Combined U-series and ESR analyses of Oryx sp. teeth indicate that the assemblage is Middle Pleistocene in age and dates to ca. 500 ka. The identified fauna is a biogeographical admixture that consists of likely endemics and taxa of African and Eurasian affinity and includes extinct and extant (or related Pleistocene forms of) mammals (Palaeoloxodon cf. recki, Panthera cf. gombaszogenis, Equus hemionus, cf. Crocuta crocuta, Vulpes sp., Canis anthus, Oryx sp.), the first Pleistocene records of birds from the Arabian Peninsula (Struthio sp., Neophron percnopterus, Milvus cf. migrans, Tachybaptus sp. Anas sp., Pterocles orientalis, Motacilla cf. alba) and reptiles (Varanidae/Uromastyx sp.). We infer that the assemblage reflects mortality in populations of herbivorous animals and their predators and scavengers that were attracted to freshwater and plant resources in the inter-dune basin. At present, there is no evidence to suggest hominin agency in the accumulation of the bone assemblages. The inferred ecological characteristics of the taxa recovered indicate the presence, at least periodically, of substantial water-bodies and open grassland habitats