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Background: Early non-infectious complications at initiation of peritoneal dialysis (PD) are a major burden with unknown long-term impacts on individuals. Methods: Prospective multicentre cohort study using univariable and multivariable Cox regression to identity mortality risk and PD discontinuation risk in those with and without non-infectious complications. All individuals commencing PD between 1 January 2014 and 31 December 2018, registered in the New Zealand Peritoneal Dialysis Registry (NZPDR) were followed up to 31 December 2020. Early non-infectious complications defined as functional, catheter-related, exit-site dialysate leak or anatomical leak complications occurring within 30 days of initiation of PD. Primary outcomes were patient survival and time on PD therapy. Secondary outcomes were peritonitis free survival, first PD catheter survival and catheter tunnel infection free survival. Results: Of 1596 individuals included in the study, 102 experienced an early non-infectious complication. Multivariable analysis demonstrated these complications were associated with higher risk of overall mortality (hazard ratio (HR) 1.71; 95% confidence interval (CI) 1.21–2.44), PD discontinuation (HR 1.84; 95% CI 1.41–2.41) and first catheter failure (HR 2.89; 95% CI 2.28–3.66). No difference was found for risk of development of first peritonitis episode or catheter tunnel infection. Mortality risk was associated with functional and exit-site dialysate leak complications and continued beyond 180 days. Risk of PD discontinuation and first catheter loss were associated with catheter and functional complications in the first 180 days. Conclusion: Early non-infectious complications are associated with long-term mortality risk. Further research in risk factors and causes of early non-infectious complications are required.

In general, fast-food organizations typically have distinctive ways of managing their business operations and achieving their corporate goals and objectives. The companies used marketing strategies to bring the organization’s mission and vision to life. Because these were influenced by the expanding population, trends, consumer behavior, internal and external factors in various situations, such as the most recent pandemic impact in 2020 continuing until 2021, many business models were introduced, adjusted, or replicated over the course of years. This study focuses on various business techniques and tactics that are crucial for the survival and sustainability of the fast-food industry and for competing against recently introduced rivals in the expanding food chain sector. This investigation will serve as a Quantitative Documentary Analysis through Data Mining. To sum it up, this research will offer suggestions on how to sell fast-food chains domestically, develop internationally, and, most importantly, ensure the survival of the company.

Under the rapid development of Phnom Penh, the pollutants control from different sources intothe main natural wetland, Tamouk lake is consequentially required for its ecosystem as well as thesustainable development. Therefore, this work aims to investigate the distribution of thepollutants from the urban canal and aquaculture farm to Tamouk lake through the analysis ofwater quality in both dry and rainy seasons. Twelve sampling sites, i.e., two from urban canals, onefrom aquaculture farm, and nine from the investigated lake, were selected for their water qualityassessment. As the results from both seasonal analyses, the maximum concentrations of totalsuspended solids (TSS), chemical oxygen demand (COD), and ammonia (NH3+) of the effluentfrom aquaculture farm and urban canal to the lake range of 107-134 mg l-1, 76-184 mg l-1, and 8.5-14.9mg l-1 in the dry season and 105-263mg l-1, 75-140 mg l-1, and 7.5-9.2 mg L-1in the rainy season,respectively. In addition, TSS and COD in the lake were only 72-93 mg l-1and 46-77mg l-1 of bothseasons, respectively, whereas NH3+ was estimated to be 7-14 times lower than that in urban canaland aquaculture farms. According to the result analysis, the lake’s water pollution was mainlycontributed by the discharge from the urban canal and aquaculture farm in both seasons. Higherrelease of pollutants from many sources during the rainy season could compensate for rainwater’sdilution effect, resulting in the high remaining of organic and nitrogen in lake water. Hence, toreduce the risk of the lake water to humans and ecosystems, the effluent from aquaculture farmsand urban water is highly suggested to have a proper treatment before discharging to the lake.

ispartof: IEEE Journal of Emerging and Selected Topics in Industrial Electronics vol:3 issue:3 pages:797-808 status: published

Purpose of reviewPatients, providers, and trainees should understand the current types of asynchronous technologies that can be used to enhance the delivery and accessibility of mental health care. Asynchronous telepsychiatry (ATP) removes the need for real time communication between the clinician and patient, which improves efficiency and enables quality specialty care. ATP can be applied as distinct consultative and supervisory models in clinician-to-clinician, clinician-to-patient, and patient-to-mobile health settings.Recent findingsThis review is based on research literature and the authors' clinical and medical training, using experiences with asynchronous telepsychiatry from before, during, and after the COVID-19 pandemic. Our studies demonstrate that ATP provides positive outcomes in the clinician-to-patient model with demonstrated feasibility, outcomes and patient satisfaction. One author's medical education experience in the Philippines during COVID-19 highlights the potential to utilize asynchronous technology in areas with limitations to online learning. We emphasize the need to teach media skills literacy around mental health to students, coaches, therapists, and clinicians when advocating for mental well-being. Several studies have demonstrated the feasibility of incorporating asynchronous e-tools such as self-guided multimedia and artificial intelligence for data collection at the clinician-to-clinician and patient-to-mobile health level. In addition, we offer fresh perspectives on recent trends in asynchronous telehealth in wellness, applying concepts such as "tele-exercise" and "tele-yoga."SummaryAsynchronous technologies continue to be integrated into mental health care services and research. Future research must ensure that the design and the usability of this technology puts the patient and provider first.

Myelin repair is an unrealized therapeutic goal in the treatment of multiple sclerosis (MS). Uncertainty remains about the optimal techniques for assessing therapeutic efficacy and imaging biomarkers are required to measure and corroborate myelin restoration. We analyzed myelin water fraction imaging from ReBUILD, a double-blind, randomized placebo-controlled (delayed treatment) remyelination trial, that showed a significant reduction in VEP latency in patients with MS. We focused on brain regions rich in myelin. Fifty MS subjects in two arms underwent 3T MRI at baseline and months 3 and 5. Half of the cohort was randomly assigned to receive treatment from baseline through 3 mo, whereas the other half received treatment from 3 mo to 5 mo post-baseline. We computed myelin water fraction changes occurring in normal-appearing white matter of corpus callosum, optic radiations, and corticospinal tracts. An increase in myelin water fraction was documented in the normal-appearing white matter of the corpus callosum, in correspondence with the administration of the remyelinating treatment clemastine. This study provides direct, biologically validated imaging-based evidence of medically induced myelin repair. Moreover, our work strongly suggests that significant myelin repair occurs outside of lesions. We therefore propose myelin water fraction within the normal-appearing white matter of the corpus callosum as a biomarker for clinical trials looking at remyelination.

Many biomarkers in clinical neuroscience lack pathological certification. This issue is potentially a significant contributor to the limited success of neuroprotective and neurorestorative therapies for human neurological disease—and is evident even in areas with therapeutic promise such as myelin repair. Despite the identification of promising remyelinating candidates, biologically validated methods to demonstrate therapeutic efficacy or provide robust preclinical evidence of remyelination in the CNS are lacking. Therapies with potential to remyelinate the CNS constitute one of the most promising and highly anticipated therapeutic developments in the pipeline to treat multiple sclerosis and other demyelinating diseases. The optic nerve has been proposed as an informative pathway to monitor remyelination in animals and human subjects. Recent clinical trials using visual evoked potential have had promising results, but without unequivocal evidence about the cellular and molecular basis for signal changes on visual evoked potential, the interpretation of these trials is constrained. The visual evoked potential was originally developed and used in the clinic as a diagnostic tool but its use as a quantitative method for assessing therapeutic response requires certification of its biological specificity. Here, using the tools of experimental pathology we demonstrate that quantitative measurements of myelination using both histopathological measures of nodal structure and ultrastructural assessments correspond to visual evoked potential latency in both inflammatory and chemical models of demyelination. Visual evoked potential latency improves after treatment with a tool remyelinating compound (clemastine), mirroring both quantitative and qualitative myelin assessment. Furthermore, clemastine does not improve visual evoked potential latency following demyelinating injury when administered to a transgenic animal incapable of forming new myelin. Therefore, using the capacity for therapeutic enhancement and biological loss of function we demonstrate conclusively that visual evoked potential measures myelin status and is thereby a validated tool for preclinical verification of remyelination.

Global migration trends are accelerating population admixture. Increasing population diversity met with minority health disparities necessitates thoughtful training of health professional students. Health professional accreditation standards emphasize pharmacogenomics and clinical cultural competency (CCC); however, published studies focus on students’ knowledge in pharmacogenomics alone. This report reviews considerations for integrating CCC into required pharmacogenomic education in pharmacy and other health disciplines. By coupling both topics during didactic training and active learning exercises repeated throughout the existing curriculum, students can become adept at these individualized patient care skills and retain their knowledge into their careers. Moving beyond race as a proxy for healthcare decision-making, the CCC of clinicians coupled with patients’ genetic test results could empower clinicians to address health disparities and facilitate discussions about the role of race in clinical practice. Ultimately, an integrated approach of teaching pharmacogenomics and CCC could dismantle race-norming or race-based clinical practices.

There is currently a lack of precise predictive biomarkers for patient selection in clinical trials of inhibitors targeting replication stress (RS) response proteins ATR and CHK1. The objective of this study was to identify novel predictive biomarkers for the response to these agents in treating non–small cell lung cancer (NSCLC). A genome-wide loss-of-function screen revealed that tumor suppressor PPP2R2A, a B regulatory subunit of protein phosphatase 2 (PP2A), determines sensitivity to CHK1 inhibition. A synthetic lethal interaction between PPP2R2A deficiency and ATR or CHK1 inhibition was observed in NSCLC in vitro and in vivo and was independent of p53 status. ATR and CHK1 inhibition resulted in significantly increased levels of RS and altered replication dynamics, particularly in PPP2R2A-deficient NSCLC cells. Mechanistically, PPP2R2A negatively regulated translation of oncogene c-Myc protein. c-Myc activity was required for PPP2R2A deficiency-induced alterations of replication initiation/RS and sensitivity to ATR/CHK1 inhibitors. We conclude that PPP2R2A deficiency elevates RS by upregulating c-Myc activity, rendering cells reliant on the ATR/CHK1 axis for survival. Our studies show a novel synthetic lethal interaction and identify PPP2R2A as a potential new predictive biomarker for patient stratification in the clinical use of ATR and CHK1 inhibitors.Significance:This study reveals new approaches to specifically target PPP2R2A-deficient lung cancer cells and provides a novel biomarker that will significantly improve treatment outcome with ATR and CHK1 inhibitors.

Supplementary Materials and Methods.

Solar-driven bioelectrosynthesis represents a promising approach for converting abundant resources into value-added chemicals with renewable energy. Microorganisms powered by electrochemical reducing equivalents assimilate CO

Background/ObjectiveThe most significant adverse events following SARS-CoV-2 vaccination are myocarditis and pericarditis. Myositis and dermatomyositis have been reported following SARS-CoV-2 infection, but vaccine-induced dermatomyositis (DM) has not been reported. Our case series aimed to characterize new onset dermatomyositis or disease-related flares following SARS-CoV-2 vaccination.Materials and methodsA total of 53 patients from our institution with a new or pre-existing diagnosis of DM were recruited and consented. Phone interviews were conducted to obtain vaccination status and symptoms following vaccination. Electronic medical records were reviewed to extract age, sex, autoantibody profiles, comorbidities, immunomodulatory therapies, creatine kinase (CK) values, and SARS-CoV-2 vaccination dates from the provincial vaccination registry. For patients who reported disease flares, records were reviewed for the onset and nature of symptoms, extent of organ involvement and changes in immunomodulation.ResultsOn average, patients received 2.62 vaccine doses (range 1–3 doses). A total of 3 of 51 patients (5.88%) experienced dermatomyositis symptoms following vaccination. Two patients were newly diagnosed with dermatomyositis, one requiring hospitalization. Reported symptom onset following vaccination ranged from 1 to 30 days. Of note, all of these patients had normal CK values, even though there was muscle biopsy-confirmed myositis in one patient. Eight patients in the cohort (15.1%) had asymptomatic CK elevation (ConclusionNew onset dermatomyositis or flare up of pre-existing dermatomyositis may be a rare complication in SARS-CoV-2 vaccination although no studies can support a true correlation. Several pathophysiologic mechanisms are proposed.

We report that the neurotrophin receptor p75 contributes to sensory neuron survival through the regulation of cholesterol metabolism in Schwann cells. Selective deletion of p75 in mouse Schwann cells of either sex resulted in a 30% loss of dorsal root ganglia (DRG) neurons and diminished thermal sensitivity. P75 regulates Schwann cell cholesterol biosynthesis in response to BDNF, forming a co-receptor complex with ErbB2 and activating ErbB2-mediated stimulation of sterol regulatory element binding protein 2 (SREBP2), a master regulator of cholesterol synthesis. Schwann cells lacking p75 exhibited decreased activation of SREBP2 and a reduction in 7-dehydrocholesterol (7-DHC) reductase (DHCR7) expression, resulting in accumulation of the neurotoxic intermediate, 7-dehyrocholesterol in the sciatic nerve. Restoration of DHCR7 in p75 null Schwann cells in mice significantly attenuated DRG neuron loss. Together, these results reveal a mechanism by which the disruption of lipid metabolism in glial cells negatively influences sensory neuron survival, which has implications for a wide range of peripheral neuropathies.SIGNIFICANCE STATEMENTAlthough expressed in Schwann cells, the role of p75 in myelination has remained unresolved in part because of its dual expression in sensory neurons that Schwann cells myelinate. When p75 was deleted selectively among Schwann cells, myelination was minimally affected, while sensory neuron survival was reduced by 30%. The phenotype is mainly due to dysregulation of cholesterol biosynthesis in p75-deficient Schwann cells, leading to an accumulation of neurotoxic cholesterol precursor, 7-dehydrocholesterol (7-DHC). Mechanism-wise, we discovered that in response to BDNF, p75 recruits and activates ErbB2 independently of ErbB3, thereby stimulating the master regulator, sterol regulatory element binding protein 2 (SREBP2). These results together highlight a novel role of p75 in Schwann cells in regulating DRG neuron survival by orchestrating proper cholesterol metabolism.

Brachiocephalic arteriovenous fistulas (AVF) makeup approximately one third of prevalent dialysis vascular accesses. The most common cause of malfunction with this access is cephalic arch stenosis (CAS). The accepted requirement for treatment of a venous stenosis lesion is ⩾50% stenosis associated with hemodynamically abnormalities. However, the correlation between percentage stenosis and a clinically significant decrease in access blood flow (Qa) is low. The critical parameter is the absolute minimal luminal diameter (MLD) of the lesion. This is the parameter that exerts the key restrictive effect on Qa and results in hemodynamic and functional implications for the access. CAS is the result of low wall shear stress (WSS) resulting from the effects of increased blood flow and the unique anatomical configuration of the CAS. Decrease in WSS has a linear relationship to increased blood flow velocity and neointimal hyperplasia exhibits an inverse relationship with WSS. The result is a stenotic lesion. The presence of downstream venous stenosis causes an inflow-outflow mismatch resulting in increased pressure within the access. Qa in this situation may be decreased, increased, or within a normal range. Over time, the increased intraluminal pressure can result in marked aneurysmal changes within the AVF, difficulties with cannulation and the dialysis treatment, and ultimately, increasing risk of access thrombosis. Complete characterization of the lesion both hemodynamically and anatomically should be the first step in developing a strategy for management. This requires both access flow measurement and angiographic imaging. Patients with CAS present a relatively broad spectrum as relates to both of these parameters. These data should be used to determine whether primary treatment of CAS should be directed toward the anatomical lesion (small MLD and low Qa) or the pathophysiology (large MLD and high Qa).

Neural representations have emerged as a new paradigm for applications in rendering, imaging, geometric modeling, and simulation. Compared to traditional representations such as meshes, point clouds, or volumes they can be flexibly incorporated into differentiable learning-based pipelines. While recent improvements to neural representations now make it possible to represent signals with fine details at moderate resolutions (e.g., for images and 3D shapes), adequately representing large-scale or complex scenes has proven a challenge. Current neural representations fail to accurately represent images at resolutions greater than a megapixel or 3D scenes with more than a few hundred thousand polygons. Here, we introduce a new hybrid implicit-explicit network architecture and training strategy that adaptively allocates resources during training and inference based on the local complexity of a signal of interest. Our approach uses a multiscale block-coordinate decomposition, similar to a quadtree or octree, that is optimized during training. The network architecture operates in two stages: using the bulk of the network parameters, a coordinate encoder generates a feature grid in a single forward pass. Then, hundreds or thousands of samples within each block can be efficiently evaluated using a lightweight feature decoder. With this hybrid implicit-explicit network architecture, we demonstrate the first experiments that fit gigapixel images to nearly 40 dB peak signal-to-noise ratio. Notably this represents an increase in scale of over 1000x compared to the resolution of previously demonstrated image-fitting experiments. Moreover, our approach is able to represent 3D shapes significantly faster and better than previous techniques; it reduces training times from days to hours or minutes and memory requirements by over an order of magnitude., Comment: J. N. P. Martel and D. B. Lindell equally contributed to this work

Background Sarcomatoid carcinomas are extremely rare tumors made of epithelial and mesenchymal elements. They have been found in various organs, but presence in the common bile duct (CBD) has only been reported a handful of times. Insight regarding the clinical history, histopathology, treatment, and prognosis is limited. The majority of CBD sarcomatoid carcinomas have occurred in elderly women, including this case. Surgical resection is the mainstay of treatment and the roles for chemotherapy and radiation therapy are undetermined. Prognosis is variable, but generally poor. Purpose Additional information regarding sarcomatoid carcinomas of the CBD will aid in establishing a timely diagnosis and may alter treatment options and prognosis. We aim to add to the limited literature surrounding this rare CBD neoplasm. Method A 71-year-old female presented with painless jaundice, decreased appetite, and weight loss. Initial investigations showed an alkaline phosphatase (ALP) of 3075 U/L, aspartate transaminase (AST) of 507 U/L, alanine aminotransferase (ALT) of 298 U/L, total bilirubin of 325.5 µmol/L, and direct bilirubin of 254.1 µmol/L. Initial computed tomography (CT) scan done showed marked intra- and extrahepatic biliary ductal dilation with appropriate tapering and the presence of a distal CBD hyperdensity. Tissue biopsy obtained by endoscopic retrograde cholangiopancreatography (ERCP) was suspicious for a malignant peripheral nerve sheath tumor. The differential also included synovial sarcoma and sarcomatoid mesothelioma. Result(s) After multidisciplinary discussion involving hepatobiliary surgery, medical oncology, and radiation oncology, pancreaticoduodenectomy was performed; there was no role for neoadjuvant/adjuvant chemotherapy/radiation therapy. Final pathology revealed a well circumscribed mass with a narrow attachment to the posterior CBD, measuring 5.6 x 3.2 x 2.8 cm. Immunohistochemistry showed mixed differentiation with sarcomatoid, squamous, and glandular components, consistent with a sarcomatoid carcinoma. H3K27me3 expression was lost in neoplastic cells. Immunostaining showed strong expression of vimentin and weak expression of CD34, calretinin, CK5 and EMA. Post-operative course was complicated by pancreaticojejunal leak, surgical wound infection, myocardial injury, and esophageal stricturing. 14-weeks post-pancreaticoduodenectomy the patient was found to have C.difficile infection and a perforated viscus, exact location of which was not visible on imaging. Emergent laparotomy revealed a gastroduodenal leak and diffuse small bowel ischemia. The patient passed away shortly after emergent surgery. Conclusion(s) This case illustrates a rare presentation of sarcomatoid carcinoma within the CBD and highlights some of the diagnostic challenges, limited management strategies, complications, and potential poor prognosis of the disease. Further research is required to guide diagnosis and management, and ultimately improve patient outcomes. Please acknowledge all funding agencies by checking the applicable boxes below None Disclosure of Interest None Declared

Background: Delay in care of suspected stenosis or thrombosis can increase the chance of losing a functioning hemodialysis access. Access to care and resources were restricted during the COVID-19 pandemic. To evaluate the impact of the pandemic on arteriovenous fistula (AVF) and arteriovenous graft (AVG) procedures we have assessed the number and success of thrombectomies done before and during the COVID-19 pandemic. Methods: We examined all AVF and AVG angiograms with and without interventions, including thrombectomies, performed at a single center during April 2017–March 2021 (pre-COVID-19 era) and April 2020–March 2021 (COVID-19 era). Results: The proportion of procedures that were thrombectomies was higher during the COVID-19 era compared to the pre-COVID-19 era (13.3% vs 8.7%, p = 0.009). The proportion of thrombectomy procedures was higher during COVID-19 for AVF (8.2% vs 3.0%, p < 0.001) but there was no difference for AVG (26.5% vs 27%, p = 0.99). There was a trend toward a higher likelihood of unsuccessful thrombectomy during COVID-19 (33.3% vs 20.4%, p = 0.08). Conclusions: More dialysis access thromboses and unsuccessful thrombectomies were noted during the COVID-19 pandemic. This difference could be due to a delay in patients getting procedures to maintain their dialysis accesses.

Elevated neutrophil-to-lymphocyte ratio (NLR) in patients who undergo elective vascular surgery (EVS) have increased mortality independent of perioperative surgical outcome. To understand why high NLR is associated with higher mortality, we investigated neutrophil and lymphocyte transcriptome expression in patients undergoing EVS. Blood samples were collected from patients undergoing EVS and healthy donors for NLR calculation. RNA samples were isolated from patients' neutrophils and lymphocytes and divided into NLR_Low (

Background Despite many options for upper lip reconstruction, each method's advantages and disadvantages are unclear. Objective To summarize complications and functional and aesthetic outcomes of localized skin flaps for oncological reconstruction of the upper cutaneous lip (PROSPERO CRD42020157244). Methods The search was conducted in Ovid MEDLINE, Ovid EMBASE, and CENTRAL on December 14, 2019. Two reviewers screened 2,958 results for eligibility. Bias assessment was conducted using ROBINS-I criteria. Results Our search identified 12 studies reporting outcomes of V-Y advancement, ergotrid, rotation, Karapandzic, alar crescent, and propeller facial artery perforator flaps. Flap complications (infection, hemorrhage/hematoma, wound dehiscence, and flap necrosis) ranged from 0% to 7.69%. Functional outcomes (salivary continence, microstomia, and paresthesia) were poorest for Karapandzic flaps. Aesthetic outcomes, when reported, stated satisfaction rates greater than 90%. V-Y advancement flaps reported the highest rates of poor scarring (0%-20%) and need for revision surgery (0%-46.7%). Conclusion Our results provide dermatologic surgeons an overview of upper cutaneous lip flap outcomes reported in the literature. In general, we noted high patient satisfaction rates and low complication rates. Additional research into outcomes of other commonly used flaps is needed. Standardization of reported outcomes could allow further comparison across different flaps or across studies of the same flap.

Myelin, multilayered lipid-rich membrane extensions formed by oligodendrocytes around neuronal axons, is essential for fast and efficient action potential propagation in the central nervous system. Initially thought to be a static and immutable process, myelination is now appreciated to be a dynamic process capable of responding to and modulating neuronal function throughout life. While the importance of this type of plasticity, called adaptive myelination, is now well accepted, we are only beginning to understand the underlying cellular and molecular mechanisms by which neurons communicate experience-driven circuit activation to oligodendroglia and precisely how changes in oligodendrocytes and their myelin refine neuronal function. Here, we review recent findings addressing this reciprocal relationship in which neurons alter oligodendroglial form and oligodendrocytes conversely modulate neuronal function.

Metabolic acidosis induces osteoclastic bone resorption and inhibits osteoblastic bone formation. Previously we found that mice with a global deletion of the proton receptor OGR1 had increased bone density although both osteoblast and osteoclast activity were increased. To test whether direct effects on osteoclast OGR1 are critical for metabolic acidosis stimulated bone resorption, we generated knockout mice with an osteoclast-specific deletion of OGR1 (knockout mice). We studied bones from three-month old female mice and the differentiated osteoclasts derived from bone marrow of femurs from these knockout and wild type mice. MicroCT demonstrated increased density in tibiae and femurs but not in vertebrae of the knockout mice. Tartrate resistant acid phosphatase staining of tibia indicated a decrease in osteoclast number and surface area/bone surface from knockout compared to wild type mice. Osteoclasts derived from the marrow of knockout mice demonstrated decreased pit formation, osteoclast staining and osteoclast-specific gene expression compared to those from wild type mice. In response to metabolic acidosis, osteoclasts from knockout mice had decreased nuclear translocation of NFATc1, a transcriptional regulator of differentiation, and no increase in size or number compared to osteoclasts from wild type mice. Thus, loss of osteoclast OGR1 decreased both basal and metabolic acidosis-induced osteoclast activity indicating osteoclast OGR1 is important in mediating metabolic acidosis-induced bone resorption. Understanding the role of OGR1 in metabolic acidosis-induced bone resorption will provide insight into bone loss in acidotic patients with chronic kidney disease.

Solar-driven bioelectrosynthesis represents a promising approach for converting abundant resources into value-added chemicals with renewable energy. Microorganisms powered by electrochemical reducing equivalents assimilate CO 2 , H 2 O, and N 2 building blocks. However, products from autotrophic whole-cell biocatalysts are limited. Furthermore, biocatalysts tasked with N 2 reduction are constrained by simultaneous energy-intensive autotrophy. To overcome these challenges, we designed a biohybrid coculture for tandem and tunable CO 2 and N 2 fixation to value-added products, allowing the different species to distribute bioconversion steps and reduce the individual metabolic burden. This consortium involves acetogen Sporomusa ovata , which reduces CO 2 to acetate, and diazotrophic Rhodopseudomonas palustris , which uses the acetate both to fuel N 2 fixation and for the generation of a biopolyester. We demonstrate that the coculture platform provides a robust ecosystem for continuous CO 2 and N 2 fixation, and its outputs are directed by substrate gas composition. Moreover, we show the ability to support the coculture on a high–surface area silicon nanowire cathodic platform. The biohybrid coculture achieved peak faradaic efficiencies of 100, 19.1, and 6.3% for acetate, nitrogen in biomass, and ammonia, respectively, while maintaining product tunability. Finally, we established full solar to chemical conversion driven by a photovoltaic device, resulting in solar to chemical efficiencies of 1.78, 0.51, and 0.08% for acetate, nitrogenous biomass, and ammonia, correspondingly. Ultimately, our work demonstrates the ability to employ and electrochemically manipulate bacterial communities on demand to expand the suite of CO 2 and N 2 bioelectrosynthesis products.

Introduction HGS has been shown to be associated with adverse outcomes in a wide range of conditions. It has also been found to be associated with bone mineral density and is inversely associated with risk of osteoporotic fractures. The aim of this study was to determine the association between HGS and 10 year probability of sustaining a major osteoporotic fractures in older inpatient and to evaluate the effect of gender on this association. Method This was a cross-sectional, observational analysis of older patients admitted into hospital between September and November 2021. HGS was measured in these patients using the JAMAR hydraulic hand held dynamometer. The Southampton protocol was used. The FRAX UK tool (without BMD) was used to calculate 10 year probability of major osteoporotic fractures. Patients were included if they were 60 years and above. Younger patients were excluded as were stroke patients. Patients with incomplete data were excluded from analysis. The SPSS 27 package was used for statistical analysis. Baseline characteristics were calculated using descriptive statistics. Pearson’s correlation coefficient and linear regression were used to calculate correlation. Results 104 patients were analysed—41 males and 63 females. Mean age was 83 years (SD 8.2). Grip strength was inversely correlated with FRAX UK in predicting 10 year probability of major osteoporotic fractures in all patients, male patients and female patients (r = −0.452; p Conclusion Grip strength is negatively associated with increased probability of major osteoporotic fractures in older inpatients. Reference(s) Ma Y, Fu L, Jia L, et al. Muscle strength rather than muscle mass is associated with osteoporosis in older Chinese adults. J Formos Med Assoc. 2018;117(2):101–108. doi:10.1016/j.jfma.2017.03.004

Introduction Frailty and sarcopenia have been shown to significantly increase the risk of falls, traumatic hip fractures and all-cause mortality in the elderly. The assessment of frailty using a validated clinical frailty scale such as that proposed by Rockwood et al., therefore, continues to remain an important step in determining post-operative prognosis in patients undergoing hip fracture surgery. The purpose of this study was to examine the relationship between frailty and serum albumin—an independent biochemical predictor of survival in hip fracture patients (1). Method This retrospective cross-sectional study analysed 190 patients, aged above 60 years, admitted to Queen’s Hospital Burton (QHB) between the 1st January and 28th December 2019 with a newly diagnosed hip fracture. Pre-operative serum albumin levels (g/L) and Rockwood clinical frailty scores (rCFS) were recorded from electronic medical records (EMR). Using the SPSS 27 statistical package, Pearson’s correlation co-efficient and linear regression analysis were carried out using these variables. Results A total of 190 patients were included in the study (57 male, 133 female). Mean patient age was 82.2 ± 8.47 years. More than 50% of patients had a Rockwood CFS ≥5. Mean serum albumin (g/L) was 37.3 ± 6.56. A statistically significant inverse correlation was demonstrated between pre-operative serum albumin levels and Rockwood CFS (r = −0.243, p Conclusion This study showed how serum albumin, a negative acute phase reactant and marker of chronic malnutrition, is inversely associated with frailty in hip fracture patients and the important role of Rockwood CFS and pre-operative serum albumin levels in the prognostication of hip fractures in the elderly. References 1) Bohl D, Shen M, Hannon C, Fillingham Y, Darrith B, Della Valle C. Serum Albumin Predicts Survival and Postoperative Course Following Surgery for Geriatric Hip Fracture. Journal of Bone and Joint Surgery. 2017;99(24):2110–2,118.

Quantitative Systems Pharmacology (QSP) modeling is increasingly applied in the pharmaceutical industry to influence decision making across a wide range of stages from early discovery to clinical development to post-marketing activities. Development of standards for how these models are constructed, assessed, and communicated is of active interest to the modeling community and regulators but is complicated by the wide variability in the structures and intended uses of the underlying models and the diverse expertise of QSP modelers. With this in mind, the IQ Consortium conducted a survey across the pharmaceutical/biotech industry to understand current practices for QSP modeling. This article presents the survey results and provides insights into current practices and methods used by QSP practitioners based on model type and the intended use at various stages of drug development. The survey also highlights key areas for future development including better integration with statistical methods, standardization of approaches towards virtual populations, and increased use of QSP models for late-stage clinical development and regulatory submissions.

SARS-CoV-2 whole genome sequencing has played an important role in documenting the emergence of polymorphisms in the viral genome and its continuing evolution during the COVID-19 pandemic. Here we present data from over 360 patients to characterize the complex sequence diversity of individual infections identified during multiple variant surges (e.g., Alpha and Delta; requiring ≥ 80% genome coverage and ≥100X read depth). Across our survey, we observed significantly increasing SARS-CoV-2 sequence diversity during the pandemic and frequent occurrence of multiple biallelic sequence polymorphisms in all infections. This sequence polymorphism shows that SARS-CoV-2 infections are heterogeneous mixtures. Convention for reporting microbial pathogens guides investigators to report a majority consensus sequence. In our study, we found that this approach would under-report at least 79% of the observed sequence variation. As we find that this sequence heterogeneity is efficiently transmitted from donors to recipients, our findings illustrate that infection complexity must be monitored and reported more completely to understand SARS-CoV-2 infection and transmission dynamics involving both immunocompetent and immunocompromised patients. Many of the nucleotide changes that would not be reported in a majority consensus sequence have now been observed as lineage defining SNPs in Omicron BA.1 and/or BA.2 variants. This suggests that minority alleles in earlier SARS-CoV-2 infections may play an important role in the continuing evolution of new variants of concern.AUTHOR SUMMARYEvolution of the virus causing COVID-19 (SARS-CoV-2) has been associated with significant transmission surges. With evolution of SARS-CoV-2, evidence has accumulated regarding increased transmissibility of lineages, varying severity of illness, evasion of vaccines and diagnostic tests. Continuous tracking of SARS-CoV-2 lineage evolution distills very large and complex viral sequence data sets down to consensus sequences that report the majority nucleotide at each of over 29,000 positions in the SARS-CoV-2 genome. We observe that this eliminates considerable sequence variation and leads to a significant underestimation of SARS-CoV-2 infection diversity and transmission complexity. Additionally, concentration on the majority consensus sequence diverts attention from genetic variation that may contribute significantly to the continuing evolution of the COVID-19 pandemic.

A mega fistula can be defined as generalized aneurysmal dilatation of arteriovenous fistula. Mega fistulae can lead to complications like high output cardiac failure, steal syndrome, skin ulceration and rupture. We describe a series of ten patients who were referred to our interventional nephrology practice for evaluation of mega fistula which had not been in use for a long time. Nine out of ten patients were post-transplant while one was pre dialysis. Five patients had Radiocephalic while four had Brachiocephalic and one had Brachial artery to Median Cubital vein fistula. All except one patient had severe outflow stenosis. The most common site of stenosis in Radiocepahlic and Brachiocepahlic fistula was cephalic vein at the elbow and cephalic arch respectively. Half of the patients had chronic total occlusion of the outflow vein. Successful angioplasty was done in only two patients. Seven patients underwent ligation while one had spontaneous thrombosis of the fistula. None of the patients had regular surveillance of their access for a long time as they were not on dialysis. Unrecognized and uncorrected outflow stenosis over a long time period can lead to creation of mega fistula. Once a mega fistula develops there are not many treatment options other than ligation. This leads to loss of the access which might be needed in future. Continuous access surveillance in patients who are not on dialysis is important to prevent complications like mega fistula.

This article presents a CMOS 2-in-1 relative humidity (RH) and temperature (Temp) sensor. A single analog front-end (AFE) interfaces two on-chip transducers and converts the resistance ( ${\propto }$ Temp) and capacitance ( ${\propto }$ RH) into a time-based signal. This conversion occurs with high linearity (±10 ppm error) across the industrial temperature range (−40 to +85 °C) through a frequency-locked loop (FLL). An incomplete-settling, switched-capacitor-based Wheatstone bridge is proposed to sense the ${R}$ and ${C}$ transducers in a power-efficient fashion. The FLL output is digitized by a low-power, time-to-digital converter (TDC) that has high resolution due to the inherent quantization noise shaping. Implemented in a 0.18- $\mu \text{m}$ CMOS process, this AFE consumes 15.6 $\mu \text{W}$ achieving a 2-mK temperature resolution over the industrial temperature range and 0.0073% RH resolution from 10 to 95 %RH. This is the first reported ${R}$ & ${C}$ -to-digital converter (RCDC) with a single, unified AFE and achieves excellent resolution figure-of-merits (FOMs) when normalized to temperature (62 fJ $\cdot \text{K}^{2}$ ) and RH [0.83 pJ $\cdot $ (%RH)2].

Autoreactive B cell-derived antibodies form immune complexes that likely play a pathogenic role in autoimmune diseases. In systemic lupus erythematosus (SLE), these antibodies bind Fc receptors on myeloid cells and induce proinflammatory cytokine production by monocytes and NETosis by neutrophils. Bruton's tyrosine kinase (BTK) is a non-receptor tyrosine kinase that signals downstream of Fc receptors and plays a transduction role in antibody expression following B cell activation. Given the roles of BTK in both the production and sensing of autoreactive antibodies, inhibitors of BTK kinase activity may provide therapeutic value to patients suffering from autoantibody-driven immune disorders. Starting from an in-house proprietary screening hit followed by structure-based rational design, we have identified a potent, reversible BTK inhibitor, BIIB068 (1), which demonstrated good kinome selectivity with good overall drug-like properties for oral dosing, was well tolerated across preclinical species at pharmacologically relevant doses with good ADME properties, and achieved >90% inhibition of BTK phosphorylation (pBTK) in humans.

Tujuan penelitian ini adalah untuk menguji efektifitas penggunaan rantai pengaman pada rangkaian kereta. Penelitian ini menggunakan jenis penelitian kualitatif dengan pendekatan analisis deskriptif. Data yang digunakan berjenis data kualitatif berupa data primer dan data sekunder yang digunakan sebagai petunjuk untuk mengetahui seberapa pentingnya penggunaan rantai pengaman dan kelayakan alat perangkai yang digunakan pada saat ini untuk menarik rangkaian kereta serta sistem pengereman. Berdasarkan hasil analisa dan pembahasan yang telah dilakukan maka dapat diambil kesimpulan sebagai berikut: 1) Putusnya rangkaian kereta dapat terjadi apabila tidak sesuainya prosedur perawatan yang dilakukan dengan semestinya, sehingga membuat menurunnya kualitas atau kemampuan dari sarana dan prasarana yang tersedia; 2) Alat perangkai otomatis tetap kuat untuk menarik rangkaian pada kelandaian 33 % dengan kecepatan maksimal 35 km/jam; 3) Bila terjadi putusnya alat perangkai maka akan terjadi sistem pengereman otomatis fail safe yang menurut perhitungan tidak larat dan tidak tergelincir dan dapat untuk menghentikan kereta pada kelandaian 33 %; dan 4) Gaya tarik maksimal yang bekerja pada rantai pengaman hanya sebesar14.700 kg dimana tidak akan kuat untuk menarik beban kereta pada kelandaian 33% sebesar 16.069 kg sehingga akan terputus.

BackgroundChronic demyelination is a major contributor to axonal vulnerability in multiple sclerosis (MS). Therefore, remyelination could provide a potent neuroprotective strategy. The ReBUILD trial was the first study showing evidence for successful remyelination following treatment with clemastine in people with MS (pwMS) with no evidence of disease activity or progression (NEDAP). Whether remyelination was associated with neuroprotection remains unexplored.MethodsPlasma neurofilament light chain (NfL) levels were measured from ReBUILD trial’s participants. Mixed linear effect models were fit for individual patients, epoch and longitudinal measurements to compare NfL concentrations between samples collected during the active and placebo treatment period.ResultsNfL concentrations were 9.6% lower in samples collected during the active treatment with clemastine (n=53, geometric mean=6.33 pg/mL) compared to samples collected during treatment with placebo (n=73, 7.00 pg/mL) (B=−0.035 [−0.068 to −0.001], p=0.041). Applying age- and body mass index-standardised NfL Z-scores and percentiles revealed similar results (0.04 vs 0.35, and 27.5 vs 33.3, p=0.023 and 0.042, respectively). Higher NfL concentrations were associated with more delayed P100 latencies (B=1.33 [0.26 to 2.41], p=0.015). In addition, improvement of P100 latencies between visits was associated with a trend for lower NfL values (B=0.003 [−0.0004 to 0.007], p=0.081). Based on a Cohen’s d of 0.248, a future 1:1 parallel-arm placebo-controlled study using a remyelinating agent with comparable effect as clemastine would need 202 subjects per group to achieve 80% power.ConclusionsIn pwMS, treatment with the remyelinating agent clemastine was associated with a reduction of blood NfL, suggesting that neuroprotection is achievable and measurable with therapeutic remyelination.Trial registration numberNCT02040298.

Objective:To investigate a cluster of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections in employees working on 1 floor of a hospital administration building.Methods:Contact tracing was performed to identify potential exposures and all employees were tested for SARS-CoV-2. Whole-genome sequencing was performed to determine the relatedness of SARS-CoV-2 samples from infected personnel and from control cases in the healthcare system with coronavirus disease 2019 (COVID-19) during the same period. Carbon dioxide levels were measured during a workday to assess adequacy of ventilation; readings >800 parts per million (ppm) were considered an indication of suboptimal ventilation. To assess the potential for airborne transmission, DNA-barcoded aerosols were released, and real-time polymerase chain reaction was used to quantify particles recovered from air samples in multiple locations.Results:Between December 22, 2020, and January 8, 2021, 17 coworkers tested positive for SARS-CoV-2, including 13 symptomatic and 4 asymptomatic individuals. Of the 5 cluster SARS-CoV-2 samples sequenced, 3 were genetically related, but these employees denied higher-risk contacts with one another. None of the sequences from the cluster were genetically related to the 17 control sequences of SARS-CoV-2. Carbon dioxide levels increased during a workday but never exceeded 800 ppm. DNA-barcoded aerosol particles were dispersed from the sites of release to locations throughout the floor; 20% of air samples had >1 log10 particles.Conclusions:In a hospital administration building outbreak, sequencing of SARS-CoV-2 confirmed transmission among coworkers. Transmission occurred despite the absence of higher-risk exposures and in a setting with adequate ventilation based on monitoring of carbon dioxide levels.