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Facemasks as personal protective equipment play a significant role in helping prevent the spread of viruses during the COVID-19 pandemic. A desired reusable fabric facemask should strike a balance of water repellency, good filtration efficiency (FE), breathability, and mechanical robustness against washing cycles. Despite significant efforts in testing various commercial fabric materials for filtration efficiency, few have investigated fabric performance as a function of the fiber/yarn morphology and wettability of the fabric itself. In this study, we examine commercial fabrics with Janus-like behaviors to determine the best reusable fabric facemask materials by understanding the roles of morphology, porosity, and wettability of the fabric on its overall performance. We find that the outer layer of the diaper fabric consisted of laminated polyurethane, which is hydrophobic, has low porosity (∼5%) and tightly woven yarn structures, and shows the highest overall FE (up to 54%) in the submicron particle size range (0.03-0.6 μm) among the fabrics tested. Fabric layers with higher porosity lead to lower-pressure drops, indicating higher breathability but lower FE. Tightly woven waterproof rainwear fabrics perform the best after 10 washing cycles, remaining intact morphologically with only a 2-5% drop in the overall FE in the submicron particle size range, whereas other knitted fabric layers become loosened and the laminated polyurethane thin film on the diaper fabric is wrinkled. In comparison, the surgical masks and N95 respirators made from nonwoven polypropylene (PP) fibers see over a 30% decline in the overall FE after 10 washing cycles. Overall, we find that tightly woven Janus fabrics consisting of a low porosity, a hydrophobic outer layer, and a high porosity and hydrophilic inner layer offer the best performance among the fabrics tested as they can generate a high overall FE, achieve good breathability, and maintain fabric morphology and performance over multiple washing cycles.

Antibiotics are a vital component of global health. By killing or inhibiting the growth of bacteria, antibiotics treat infections like pneumonia, staph, and tuberculosis. By preventing infections, they enable major medical procedures such as surgeries and chemotherapy. However, bacteria are becoming increasingly resistant to current antibiotics, causing an estimated 34,000 deaths annually in the US. Left unchecked, antibiotic resistance will have major public health consequences, causing over 5 million deaths each year by 2050. Major causes of this crisis are the misuse of existing antibiotics and the slow development of new antibiotics. To incentivize responsible use, governments and institutions are initiating education programs, mandating comprehensive hospital antibiotic stewardship programs, and funding the development of rapid diagnostics. To bring new antibiotic drugs to market, the US government and other non-governmental organizations are funding scientific research toward antibiotic development. Additional incentives are being pursued to improve the commercial viability of antibiotic development and protect drug developers from the unique challenges of the antibiotic market. With diligent efforts to improve responsible use and encourage novel antibiotic drug discovery, we can decrease the global disease burden, save money, and save lives.

This paper describe our team’s experience using minimega, a network emulation system using node and network virtualization, to support evaluation of a set of networked and distributed systems for topology discovery, traffic classification and engineering in the DARPA Searchlight program [18]. We present the methodology we developed to encode network and traffic definitions into an experiment description model, and how our tools compile this model onto the underlying minimega API. We then present three cases studies which demonstrate the ability of our EDM to support experiments with diverse network topologies, diverse traffic mixes, and networks with specialized layer-2 connectivity requirements. We conclude with the overall takeaways from using minimega to support our evaluation process.

Background: Skeletal development and maintenance are complex processes known to be coordinated by multiple genetic and epigenetic signaling pathways. However, the role of long non-coding RNAs (lncRNAs), a class of crucial epigenetic regulatory molecules, has been under explored in skeletal biology. Results: Here we report a young patient with short stature, hypothalamic dysfunction and mild macrocephaly, who carries a maternally inherited 690kb deletion at Chr.1q24.2 encompassing a noncoding RNA gene, DNM3OS, embedded on the opposite strand in an intron of the DYNAMIN 3 (DNM3)gene. We show that lncRNA DNM3OS sustains the proliferation of chondrocytes independent of two co-cistronic microRNAs miR-199a and miR-214. We further show that nerve growth factor (NGF), a known factor of chondrocyte growth, is a key target of DNM3OS-mediated control of chondrocyte proliferation.Conclusion: This work demonstrates that DNM3OS is essential for preventing premature differentiation of chondrocytes required for bone growth through endochondral ossification.

Irregularly-sampled time series are characterized by non-uniform time intervals between successive measurements. Such time series naturally occur in application areas including climate science, ecology, biology, and medicine. Irregular sampling poses a great challenge for modeling this type of data as there can be substantial uncertainty about the values of the underlying temporal processes. Moreover, different time series are not necessarily synchronized or of the same length, which makes it difficult to deal with using standard machine learning methods that assume fixed-dimensional data spaces. The goal of this thesis is to develop scalable probabilistic tools for modeling a large collection of irregularly-sampled time series defined over a common time interval. We first introduce an uncertainty-aware kernel framework based on a Gaussian process (GP) representation of the time series and then demonstrate how to significantly scale up the model by linearizing the kernel with various acceleration techniques. To further reduce the computational overhead of the GP representation and improve the expressiveness of the model, we propose a generalized uncertainty-aware framework that integrates a posterior GP sampler with arbitrary black-box models including neural networks. We propose a linear time and linear space sampling algorithm and show how to efficiently train the entire framework end-to-end. To better model the uncertainty by utilizing the information from an entire dataset collectively, we reframe our task as a missing data problem that aims at learning the distribution of the latent temporal process. We first study the missing data problem under a simplified setting where the data are defined on a finite-dimensional space and introduce a model based on generative adversarial networks for learning from incomplete data. To relax the finite-dimensional constraint, we propose a unified encoder-decoder framework that can be trained as a density model or an implicit generative model. We finally introduce a specific architecture within this framework to efficiently represent and learn from irregularly-sampled continuous time series.

Acute on chronic renal failure is a common but notably broad diagnosis. We present a 64-year-old man with a history of diastolic heart failure and chronic kidney disease, admitted for an elevated creatinine. History and physical examination were suggestive of decompensated heart failure; however, the careful interpretation of urinalysis rendered the diagnosis of multiple myeloma. On renal biopsy, the patient was found to have light chain deposition disease with cast nephropathy. Combination lesions in multiple myeloma are rare and require diligent histopathology for detection, including light microscopy, immunofluorescence and electron microscopy. These patients portray different demographics, renal manifestations, oncologic characteristics and outcomes, and hence, further studies isolating these combined lesions are warranted. Abbreviations: CKD: chronic kidney disease; CN: cast nephropathy; CT: computerized tomography; EDD: electron-dense deposits; EM: electron microscopy; IF: immunofluorescence; FLC: free light chain; LC: light chain; LCDD: light chain deposition disease; MIDD: monoclonal immunoglobulin deposition disease; MM: multiple myeloma; LM: light microscopy; NGS: nodular glomerulosclerosis; κ: kappa; λ: lambda.

We report the use of the multiplexed T. gondii IgG, IgM test on plasmonic gold (pGOLD) platform in the setting of T. gondii infection by analyzing 244 sera from Nice, France (seroconversion, chronically infected, non-infected and newborns serum samples). Results were compared with commercial tests for the detection of IgG and IgM and their overall clinical final interpretation of a complete serological profile. The IgG and IgM test results on the platform were in agreement in, respectively, 95% and 93% with the commercial kits. When comparing with the overall clinical interpretation of the serological profile, the agreement reached 99.5% and 97.7% for IgG and IgM, respectively. This innovative pGOLD platform allows detection of both IgG and IgM simultaneously with only ~1 microliter of serum. The multiplexed IgG/IgM test on pGOLD platform is a strong candidate for its use in the massive screening programs for toxoplasmosis during pregnancy.

In 2017, the Surveillance, Epidemiology, and End Results (SEER) program piloted a reactive quality audit plan (r-QAP) to analyze Collaborative Stage (CS) tumor size in breast and pancreatic cancer. Preevaluation objectives were to establish procedures and analytic scope for SEER quality audits, cutoffs for data completeness/accuracy, and key decision checkpoints.Tumor size data between 2004-2014 were selected from SEER registries for pancreatic and breast cancers, and initially assessed by site and registry for completeness. Further exploration was undertaken via cross tabulation in SEER with the American Joint Committee on Cancer (AJCC) 6th edition derived T data item to evaluate discrepancies between these closely related variables.For both cancer sites, completeness improved between 2004 and 2014, with the proportion of known tumor size values increasing from 60.6% to 79.2% in pancreatic cancer and from 94.0% to 95.9% in breast cancer. Tumor size plausibility categories were established wherein any tumor over 100 mm for pancreatic cancer or over 200 mm for breast cancer were considered highly unlikely. Only 2% of pancreas tumors and 0.1% of breast tumors were implausibly large per site-specific cutoffs. Less than 2% of all tumor size values were potentially discrepant in cross-tabulation with AJCC 6th edition derived T for each site.Most tumor size values appear to fall within acceptable ranges based on r-QAP activities, and implausibly large tumor size values are rare. Different natural histories and clinical presentation for pancreatic and breast cancer illustrate the need for site-specific cutoffs. Our results indicate that there are no major quality issues in the SEER research database for the CS tumor size data item in either pancreatic or breast cancer.

Secondary hyperparathyroidism is a common complication of both chronic kidney and end-stage renal disease. Vitamin D appears to play a central role in the pathogenesis of this condition and active vitamin D replacement is usually a necessary component of its treatment. The ability to administer active vitamin D is limited by increases in calcium and phosphorus, predisposing patients to vascular calcifications and cardiovascular disease. Paricalcitol is a new vitamin D analog designed to suppress parathyroid secretion with less effect on serum levels of calcium and phosphorus. The application of paricalcitol in chronic kidney disease may slow the clinical course of secondary hyperparathyroidism and allow more effective suppression of parathyroid hormone while minimizing the concommitant risks of hypercalcemia and hyperphosphatemia. This article reviews the pathogenesis of secondary hyperparathyroidism and the data supporting the role of oral and intravenous paricalcitol in the treatment of secondary hyperparathyroidism in both chronic kidney disease and end-stage renal disease patients.

Exposure to air pollutants causes a range of adverse health effects. These harmful effects occur whenever and wherever people come into direct contact with air pollution. Therefore, individual actions that reduce the frequency, duration, and severity of personal contact with air pollution can reduce health risks. We developed a system that empowers the public with personalized information on air quality and exposure health risk. This system, the Personalised Real-Time Air Quality Informatics System for Exposure – Hong Kong (PRAISE-HK, http://praise.ust.hk/ ), is embodied in an interactive mobile application. PRAISE-HK is based on real-time data on emissions, high resolution urban morphology, meteorology, physical and chemical processes affecting pollutant transport and transformations, extensive measurements of air pollution concentrations in typical locations such as homes, schools, offices, and transportation, and big data integration of sensor monitoring to accurately estimate current and short-term forecasted street-level air quality. The street-level air quality simulation has been validated against reference monitoring data. Ongoing and planned future enhancements to PRAISE-HK include prediction of personal exposure and health response. PRAISE-HK is an example of the use of collective intelligence in a smart city to engage citizens in learning about and managing their own exposure to air pollution.

CGEA 2015 CONFERENCE ABSTRACT (EDITED). A Novel Approach to Assessing Professionalism in Preclinical Medical Students Using Paired Self- and Peer Evaluations. Amanda R. Emke, Steven Cheng, and Carolyn Dufault. CONSTRUCT: This study sought to assess the professionalism of 2nd-year medical students in the context of team-based learning.Professionalism is an important attribute for physicians and a core competency throughout medical education. Preclinical training often focuses on individual knowledge acquisition with students working only indirectly with faculty assessors. As such, the assessment of professionalism in preclinical training continues to present challenges. We propose a novel approach to preclinical assessment of medical student professionalism to address these challenges.Second-year medical students completed self- and peer assessments of professionalism in two courses (Pediatrics and Renal/Genitourinary Diseases) following a series of team-based learning exercises. Assessments were composed of nearly identical 9-point rating scales. Correlational analysis and linear regression were used to examine the associations between self- and peer assessments and the effects of predictor variables. Four subgroups were formed based on deviation from the median ratings, and logistic regression was used to assess stability of subgroup membership over time. A missing data analysis was conducted to examine differences between average peer-assessment scores as a function of selective nonparticipation.There was a significant positive correlation (r = .62, p.0001) between self-assessments completed alone and those completed at the time of peer assessment. There was also a significant positive correlation between average peer-assessment and self-assessment alone (r = .19, p.0002) and self-assessment at the time of peer assessment (r = .27, p.0001). Logistic regression revealed that subgroup membership was stable across measurement at two time points (T1 and T2) for all groups, except for members of the high self-assessment/low peer assessment at T1, who were significantly more likely to move to a new group at T2, χ(2)(3, N = 129) = 7.80, p.05. Linear regression revealed that self-assessment alone and course were significant predictors of self-assessment at the time of peer assessment (Fself_alone = 144.74, p.01 and Fcourse = 4.70, p.05), whereas average peer rating, stage (T1, T2) and academic year (13-14, 14-15) were not. Linear regression also revealed that students who completed both self-assessments had significantly higher average peer assessment ratings (average peer rating in students with both self-assessments = 8.42, no self-assessments = 8.10, self_at_peer = 8.37, self_alone = 8.28) compared to students who completed one or no self-assessments (F = 5.34, p.01).When used as a professionalism assessment within team-based learning, stand-alone and simultaneous peer and self-assessments are highly correlated within individuals across different courses. However, although self-assessment alone is a significant predictor of self-assessment made at the time of assessing one's peers, average peer assessment does not predict self-assessment. To explore this lack of predictive power, we classified students into four subgroups based on relative deviation from median peer and self-assessment scores. Group membership was found to be stable for all groups except for those initially sorted into the high self-assessment/low peer assessment subgroup. Members of this subgroup tended to move into the low self-assessment/low peer assessment group at T2, suggesting they became more accurate at self-assessing over time. A small group of individuals remained in the group that consistently rated themselves highly while their peers rated them poorly. Future studies will track these students to see if similar deviations from accurate professional self-assessment persist into the clinical years. In addition, given that students who fail to perform self-assessments had significantly lower peer assessment scores than their counterparts who completed self-assessments in this study, these students may also be at risk for similar professionalism concerns in the clinical years; follow-up studies will examine this possibility.

Phenomenon: Professionalism is integral to the role of the physician. Most professionalism assessments in medical training are delayed until clinical rotations where multisource feedback is available. This leaves a gap in student assessment portfolios and potentially delays professional development.A total of 246 second-year medical students (2013-2015) completed self- and peer assessments of professional behaviors in 2 courses following a series of Team-Based Learning exercises. Correlation and regression analyses were used to examine the alignment or misalignment in the relationship between the 2 types of assessments. Four subgroups were formed based on observed patterns of initial self- and peer assessment alignment or misalignment, and subgroup membership stability over time was assessed. A missing data analysis examined differences between average peer assessment scores as a function of selective nonparticipation.Spearman correlation demonstrated moderate to strong correlation between self-assessments completed alone (no simultaneous peer assessment) and self-assessments completed at the time of peer assessments (ρ = .59, p.0001) but weak correlation between the two self-assessments and peer assessments (alone: ρ = .13, p.013; at time of peer: ρ = .21, p.0001). Generalized estimating equation models revealed that self-assessments done alone (p.0001) were a significant predictor of self-assessments done at the time of peer. Course was also a significant predictor (p = .01) of self-assessment scores done at the time of peer. Peer assessment score was not a significant predictor. Bhapkar's test revealed subgroup membership based on the relationship between self- and peer ratings was relatively stable across Time 1 and Time 2 assessments (χ

Background Hyperphosphatemia remains a significant problem for patients requiring dialysis and is associated with increased mortality. Current treatment options include dietary restriction, dialysis, and phosphate binders. Treatment using the latter is frequently limited by cost, tolerability, and calcium loading. One open-label trial found niacinamide to be effective at decreasing serum phosphorus values in hemodialysis patients. Niacinamide may effectively reduce phosphorus levels in peritoneal dialysis (PD) patients already receiving standard phosphorus-lowering therapies. Methods An 8 week, randomized, double blind, placebo-controlled trial to evaluate the effectiveness of niacinamide to reduce plasma phosphorus levels in PD patients. Patients had to demonstrate a baseline phosphorus value > 4.9 mg/dL. Patients were randomized to niacinamide or placebo and prescribed 250 mg twice daily, with titration to 750 mg twice daily, as long as safety parameters were not violated. Phosphate binders, active vitamin D, and cinacalcet were kept constant during the study. The primary end point was change in plasma phosphorus. Secondary end points included changes in lipid parameters. Results 15 patients started on the study drug (8 niacinamide, 7 placebo) and 7 in each arm had at least one on-study phosphorus measurement. The niacinamide treatment group experienced an average 0.7 ± 0.9 mg/dL decrease in plasma phosphorus and the placebo-treated group experienced an average 0.4 ± 0.8 mg/dL increase. The treatment effect difference (1.1 mg/dL) was significant ( p = 0.037). No significant changes in high- or low-density lipoproteins or triglycerides were demonstrated. Two of the 8 patients randomized to the niacinamide treatment arm had to withdraw from the study due to drug-related adverse effects. Adverse effects may limit the use of niacinamide in PD patients. Conclusion Niacinamide, when added to standard phosphorus-lowering therapies, resulted in a modest yet statistically significant reduction in plasma phosphorus levels at 8 weeks. [ClinicalTrials.gov number NCT00508885 (ClinicalTrials.gov)]

Background and objectives: Niacinamide inhibits intestinal sodium/phosphorus transporters and reduces serum phosphorus in open-label studies. A prospective, randomized, double-blind, placebo-controlled crossover trial was performed for assessment of the safety and efficacy of niacinamide. Design, setting, participants, & measurements: Hemodialysis patients with phosphorus levels ≥5.0 mg/dl were randomly assigned to 8 wk of niacinamide or placebo, titrated from 500 to 1500 mg/d. After a 2-wk washout period, patients switched to 8 wk of the alternative therapy. Vitamin D analogs and calcimimetics were held constant; phosphorus binders were not changed unless safety criteria were met. Results: Thirty-three patients successfully completed the trial. Serum phosphorus fell significantly from 6.26 to 5.47 mg/dl with niacinamide but not with placebo (5.85 to 5.98 mg/dl). A concurrent fall in calcium-phosphorus product was seen with niacinamide, whereas serum calcium, intact parathyroid hormone, uric acid, platelet, triglyceride, LDL, and total cholesterol levels remained stable in both arms. Serum HDL levels rose with niacinamide (50 to 61 mg/dl but not with placebo. Adverse effects were similar between both groups. Among patients who were ≥80% compliant, results were similar, although the decrease in serum phosphorus with niacinamide was more pronounced (6.45 to 5.28 mg/dl) and the increase in HDL approached significance (49 to 58 mg/dl). Conclusions: In hemodialysis patients, niacinamide effectively reduces serum phosphorus when co-administered with binders and results in a potentially advantageous increase in HDL cholesterol. Further study in larger randomized trials and other chronic kidney disease populations is indicated.

Background Nephrogenic systemic fibrosis (NSF) is a newly described disorder occurring in persons with renal failure. Gadolinium-based contrast used in magnetic resonance imaging (MRI) has been suggested as a cause. A cluster of patients with NSF was investigated to identify risk factors. Limited preliminary findings from this investigation were presented in the Morbidity and Mortality Weekly Report . Study Design Matched case-control. Setting & Participants Dialysis patients with and without a diagnosis of NSF treated at an academic medical center. Predictor Exposure to gadolinium-based contrast. Outcomes & Measurements Laboratory and clinical characteristics of NSF. Results 19 of 28 cases identified at the hospital from December 2002 to August 2006 met inclusion criteria and were matched to 57 controls. In univariate analysis, receipt of gadolinium-containing MRI contrast in the preceding year (odds ratio [OR], 7.99; 95% confidence interval, 2.22 to 28.8) was associated with NSF; the measure of association increased as cumulative dose increased. Gadodiamide exposure (OR, 9.83; 95% confidence interval, 2.09 to 46.2) was associated more strongly with NSF than gadoversetamide (OR, 1.82; 95% confidence interval, 0.33 to 10.2). Although not statistically significant, cases were more likely than controls to have undergone primarily peritoneal dialysis in the preceding 6 months. There was no significant difference in receipt of high-dose recombinant erythropoietin between cases and controls. In multivariable analysis, gadolinium contrast exposure (OR, 8.97; 95% confidence interval, 1.28 to 63.0) remained significantly associated with NSF. Limitations Retrospective design, small sample size, inability to completely evaluate erythropoietin. Conclusions Receipt of gadolinium-containing MRI contrast is associated with NSF in a dose-dependent manner. The risk associated with gadolinium may differ by contrast agent and dialysis modality. Use of gadolinium-based contrast agents should be avoided when possible in patients with renal failure.

Secondary hyperparathyroidism is a common complication of patients with chronic kidney disease. Treatment with calcitriol, the active form of vitamin D, reduces parathyroid hormone levels, but may result in elevations in serum calcium and phosphorus. New vitamin D analogues have been developed to reduce parathyroid hormone secretion without concomitant hypercalcaemia and hyperphosphataemia. Recent data from studies with paricalcitol capsules, the oral formulation of 19-nor-1,25(OH)2D2, show a significant reduction in parathyroid hormone levels with no change in calcium and phosphorus levels when compared with placebo. Paricalcitol also compares favourably to other oral vitamin D analogues, effectively decreasing parathyroid secretion with less hypercalcaemia and hypercalciuria than other agents.

Secondary hyperparathyroidism (SHPT) is commonly seen in patients with chronic kidney disease (CKD). Even in early CKD, parathyroid hormone (PTH) levels are elevated, maintaining mineral homeostasis at the cost of long-term bone health. One potent stimulus for PTH secretion is a deficiency of active vitamin D. Replacement with calcitriol, the active form of vitamin D, lowers PTH but often raises calcium and phosphorus levels, predisposing patients to an increased risk of ectopic calcifications. Paricalcitol is a vitamin D analog designed to treat SHPT without raising serum calcium and phosphorus levels. The intravenous preparation of paricalcitol is used routinely in the hemodialysis population and has demonstrated a survival benefit over calcitriol in hemodialysis patients. A new oral preparation has now been developed for use in the pre-dialysis CKD population. Thus far, oral paricalcitol has been shown to reduce PTH by an average of 42% in CKD patients, while having minimal effects on serum calcium and phosphorus. While long term effects of the oral preparation have yet to be studied, emerging evidence suggests that paricalcitol mediates a variety of beneficial effects through the activation of vitamin D receptors which may result in improved survival.

Primary biliary cirrhosis frequently progresses despite treatment with ursodeoxycholic acid (UDCA), the only approved therapy. Previous studies suggested that colchicine and methotrexate may improve biochemical tests of liver function, symptoms, and liver histology. The aim of the present study was to determine if the addition of colchicine or methotrexate to UDCA would improve survival free of liver transplantation. Eighty-five patients with histologically confirmed primary biliary cirrhosis whose serum alkaline phosphatase levels were at least twice the normal level and who were not yet candidates for liver transplantation were randomly assigned to receive colchicine or methotrexate in a double-blind study. UDCA was administered to all patients after 2 years. The primary end point was survival free of liver transplantation. Patients were followed up for a total of up to 10 years or until treatment failure. Data were analyzed on an intention-to-treat basis. Transplant-free survival was similar in both groups: 0.57 for colchicine plus UDCA and 0.44 for methotrexate plus UDCA, results that are similar to those predicted by the Mayo prognostic model. Significant improvement in liver biochemical tests and liver histology was observed in a subset of patients in both treatment groups who remained in the study for all 10 years. In conclusion, neither colchcine plus UDCA nor methotrexate plus UDCA improved survival beyond that predicted by the Mayo prognostic model. However, clinical, histologic, and biochemical improvement observed among those who remained in the study for 10 years suggests a possible benefit of these drugs in a subset of patients.

Design of solid-waste management systems requires consideration of multiple alternative solutions and evaluation criteria because the systems can have complex and conflicting impacts on different stakeholders. Multiple criteria decision analysis (MCDA) has been found to be a fruitful approach to solve this design problem. In this paper, the MCDA approach is applied to solve the landfill selection problem in Regina of Saskatchewan Canada. The systematic approach of MCDA helps decision makers select the most preferable decision and provides the basis of a decision support system. The techniques that are used in this study include: 1) Simple Weighted Addition method, 2) Weighted Product method, 3) TOPSIS, 4) cooperative game theory, and 5) ELECTRE. The results generated with these methods are compared and ranked so that the most preferable solution is identified.

Hedgehog (Hh) signaling pathway plays an important role during embryonic development and pattern formation. Disruption of Hh pathway results in various developmental disorders and increasing cancer incidence. Here we provide a comprehensive review of the pathway members, focusing on how mammalian Hh regulates the Gli family of transcription factors through its downstream members, the so-called "canonical signaling pathway". Hh signaling pathway is highly conserved among species, and primary cilia plays an important role as a "signaling center" during vertebrate signal transduction. Further, in the past few years, numerous studies have shown that Hh signal can also be transduced through Gli-independent ways collectively referred to as "non-canonical signaling pathways", which can be subdivided into two modules: (i) those not requiring Smo and (ii) those downstream of Smo that do not require Gli transcription factors. Thus, we review the rapid progress on canonical and non-canonical Hh pathways.

Feeding behaviors require intricately coordinated activation among the muscles of the jaw, tongue, and face, but the neural anatomical substrates underlying such coordination remain unclear. In this study, we investigate whether the premotor circuitry of jaw and tongue motoneurons contain elements for coordination. Using a modified monosynaptic rabies virus-based transsynaptic tracing strategy, we systematically mapped premotor neurons for the jaw-closing masseter muscle and the tongue-protruding genioglossus muscle. The maps revealed that the two groups of premotor neurons are distributed in regions implicated in rhythmogenesis, descending motor control, and sensory feedback. Importantly, we discovered several premotor connection configurations that are ideally suited for coordinating bilaterally symmetric jaw movements, and for enabling co-activation of specific jaw, tongue, and facial muscles. Our findings suggest that shared premotor neurons that form specific multi-target connections with selected motoneurons are a simple and general solution to the problem of orofacial coordination. DOI: http://dx.doi.org/10.7554/eLife.02511.001, eLife digest Chewing requires highly coordinated movements of the tongue and jaw. The tongue pushes food around the mouth, keeping it within reach of the teeth, while rhythmic movements of the jaw enable the teeth to grind up food without injuring the tongue itself. However, despite the importance of tongue–jaw coordination, the neuroanatomical circuits that underlie it have not been studied in detail. Stanek et al. have now mapped these neural circuits using a cutting edge tracing technique in mice. Muscles are activated by signals from neurons called motoneurons, which are themselves activated by signals from so-called premotor neurons. To identify the neural circuits responsible for tongue–jaw coordination, Stanek et al. injected a modified version of the rabies virus into the muscles that move the jaw and/or the tongue. This modified virus, which was also labeled with a fluorescent protein, was able to jump ‘backwards’ across the junctions between the muscles and the motoneurons, and then back to the premotor neurons. The fluorescent label allowed the neural circuits to be visualized under a fluorescence microscope. It had been assumed that distinct populations of premotor neurons would control the activity of different muscles. However, when viruses labeled with red fluorescent protein were injected into the muscles on the left side of the jaw, while viruses with green labels were injected into the muscles on the right side, a number of premotor neurons were found to display both red and green fluorescence. This indicates that some premotor neurons control muscles on both sides of the jaw, providing an effective means of coordinating bilateral muscle activity. A similar sharing of premotor neurons was observed between motoneurons that regulate jaw opening and those that trigger tongue protrusion, and between those that regulate jaw closing and tongue retraction. As well as providing new insights into the neuronal circuits that control the movements of the jaw and tongue, the work of Stanek et al. may have identified a general principle—namely the sharing of premotor neurons—that could be common to other circuits that produce coordinated muscle activity. DOI: http://dx.doi.org/10.7554/eLife.02511.002

Multiprocess systems, including grid systems, multiprocessors and multicore computers, incorporate a variety of specialized hardware and software mechanisms, which speed computation, but result in complex memory behavior. As a consequence, the possible outcomes of a concurrent program can be unexpected. A memory consistency model is a description of the behaviour of such a system. Abstract memory consistency models aim to capture the concrete implementations and architectures. Therefore, formal specification of the implementation or architecture is necessary, and proofs of correspondence between the abstract and the concrete models are required. This paper provides a case study of this process. We specify a new model, partition consistency, that generalizes many existing consistency models. A concrete message-passing network model is also specified. Implementations of partition consistency on this network model are then presented and proved correct. A middle level of abstraction is utilized to facilitate the proofs. All three levels of abstraction are specified using the same framework. The paper aims to illustrate a general methodology and techniques for specifying memory consistency models and proving the correctness of their implementations.

The class of 2-bijective connection networks (2BC networks) is defined recursively as follows: Let [Formula: see text] and for [Formula: see text], let [Formula: see text] be the set of all graphs that can be constructed by taking two (possibly the same) elements [Formula: see text] and [Formula: see text] from [Formula: see text] (if we take the same element, we will assume they are two different copies and so [Formula: see text] remains empty) with two bijections [Formula: see text] and [Formula: see text] to form the graph [Formula: see text] where [Formula: see text] and [Formula: see text] such that [Formula: see text]. This class of networks includes the class of augmented cubes. We study the structural properties of the resulting graph when “many” edges are deleted from such a network. We then mention some applications.

Nephrogenic systemic fibrosis (NSF) is a debilitating disorder that affects patients with renal insufficiency. Recent evidence suggests that the development of NSF may be related to the administration of gadolinium-based contrast media (GBCM) in the setting of magnetic resonance imaging. As no treatment has consistently been effective in the management of NSF, strategies to prevent the development of this condition appear to be the best therapy. Identification of patients at greatest risk for developing NSF after exposure to GBCM is crucial. Risk factors include advanced chronic kidney disease (stages 4 and 5) and acute or chronic inflammatory events. The United States Food and Drug Administration has updated its public health advisory to include patients with moderate renal insufficiency (chronic kidney disease stage 3) as being at risk for developing NSF. However, these data require further verification and the vast majority of affected patients are already on renal replacement therapy. Another strategy in prevention may include consultation with a radiologist for imaging alternatives. If GBCM must be administered, immediate hemodialysis may be protective in patients already on hemodialysis; however, given the lack of data to support this, we do not recommend routine dialysis for patients not yet on dialysis or who are currently being treated with peritoneal dialysis. Decisions such as this should be made on a case by case basis after evaluating additional risk factors.

Purpose of review There is a high prevalence of vitamin D deficiency in the chronic kidney disease population. Vitamin D is often administered to patients to mitigate detrimental effects on bone health and mineral metabolism, though this treatment may be limited by elevations in serum calcium and phosphorus. This article reviews the basic physiology of vitamin D, the survival data in patients receiving vitamin D, and the current quandary of whether vitamin D administration is beneficial in chronic kidney disease. Recent findings Despite potential increases in serum calcium and phosphorus due to activation of vitamin D receptors in the gut, vitamin D administration has been associated with a survival benefit in recent studies. While the mechanism for this possible benefit is unknown, vitamin D administration may have effects beyond its traditional role in mineral metabolism, mediated through the activation of vitamin D receptors distributed in a variety of tissues. Summary Data currently suggests that the administration of vitamin D confers a survival benefit to patients on dialysis. There is no clear mechanism, however, to explain this association. Further research is needed to clarify the expanding role of vitamin D receptor activation, particularly in vascular calcification, and the effects of the different forms of vitamin D.

Detection of stationary foreground objects within a dynamic scene is one of the goals of a video surveillance system. A parametric background maintenance and updating scheme, based on a multiple Gaussian mixture model that operates on multiple time scales, is proposed. Each color cluster in the proposed model is assigned a weight which measures the time duration and temporal recurrence frequency of the cluster. Sudden illumination changes are handled by using an adaptive histogram template whereas gradual illumination changes are automatically resolved with the adaptive background model. Stationary foreground objects are detected by maintaining their temporal history in the dynamic scene at multiple time scales. Experimental results show that the proposed scheme performs well in three distinct real-world settings.

In the US, diabetic nephropathy accounts for the majority of chronic kidney disease (CKD). It contributes significantly to morbidity and mortality among the diabetic population1,2and accounts for approximately 40% of patients with end-stage renal disease.3The earliest manifestation of renal involvement in diabetes is the presence of microalbuminuria, as defined by urine albumin excretion of 30–300mg/day.4Progression to overt proteinuria (urine albumin excretion greater than 300mg/day) and diabetic nephropathy occur more frequently in those with poor glycemic control, glomerular hyperfiltration, and hypertension.5

In this study, a hybrid foundation concept is presented. The concept combines a skirted mat with a suction caisson to enable self-installation and suction-induced preloading of the footing. To quantify the increase in the combined Vertical (V), Horizontal (H) and Moment (M) loading capacity resulting from the addition of the caisson, centrifuge experiments have been conducted. A series of swipe tests were performed on the hybrid foundation of a particular geometry to explore its VHM yield envelope under different vertical loads. A newly developed VHM loading apparatus, with independent control of the in-plane vertical, horizontal and rotational degrees-of-freedom, especially developed to investigate the combined VHM behaviours for offshore foundations, was used. The results were interpreted as an analytical three-dimensional surface. It is demonstrated that the H and M bearing capacities are nearly identical for different vertical load levels once the footing has been pushed to the depth of its skirt. © 2010 Taylor & Francis Group, London.