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Blue-light cystoscopy with intravesical hexyl-aminolevulinate has been shown to improve identification of bladder carcinoma. The application of photodynamic techniques in the upper tract has not been well studied. We present a patient with a patulous ureteral orifice allowing for dwelling of photodynamic reagent and cystoscopic evaluation of the distal ureter. This case was significant for blue light fluorescent, biopsy proven upper tract carcinoma in situ that otherwise would have been a benign examination using traditional white light technique. Future work should be done to study the use of photodynamic techniques in the evaluation of upper tract malignancies.

Background:. Patients with Robin sequence (RS) are often thought to be at high-risk for airway complications after cleft palate repair, and may be routinely admitted to the intensive care unit after surgery. This study compares frequency of postoperative airway events in patients with and without RS undergoing palatoplasty, and assesses potential risk factors for needing intensive care. Methods:. A matched cohort study of patients with and without RS undergoing palatoplasty from February 2014 to February 2022 was conducted. Variables of interest included prior management of micrognathia, comorbidities, polysomnography, age and weight at the time of palatoplasty, operative techniques, intubation difficulty, anesthesia duration, and postoperative airway management. Airway events were defined as airway edema, secretions, stridor, laryngospasm, obstruction, and/or desaturation requiring intervention. Logistic regression was performed to identify factors predictive of airway events. Results:. Thirty-three patients with RS and 33 controls were included. There were no statistically significant differences in airway events between groups (eight RS, four controls, P = 0.30). Anesthetic duration over 318 minutes was associated with increased risk of postoperative airway events [(OR) 1.02 (1.00–1.04) (P = 0.04)] for patients with RS, but not for patients in the control cohort. Conclusions:. Postoperative intensive care unit admission is not universally necessary for patients with RS after palatoplasty if intubation was straightforward and there were no concomitant procedures being performed. Patients with longer anesthesia durations were more likely to have postoperative airway events and may need a higher level of care postoperatively.

The distribution of fiber diameters plays a crucial role in the transport and sound absorbing properties of a three-dimensional random fibrous (3D-RF) medium. Conventionally, volume-weighted averaging of fiber diameters has been utilized as an appropriate microstructural descriptor to predict the static viscous permeability of 3D-RF media. However, the long wavelength acoustical properties of a 3D-RF medium are also sensitive to the smallest fibers, this is particularly true in the high-frequency regime. In our recent research, we demonstrated that an inverse volume-weighted averaging of fiber diameters can effectively serve as a complementary microstructural descriptor to capture the high-frequency behavior of polydisperse fibrous media. In the present work, we reexamine the identification of two representative volume elements (RVEs) which relies on the reconstruction of 3D-RF microstructures having volume-weighted and inverse-volume weighted averaged fiber diameters, respectively in the low-frequency and high frequency regimes. We investigate the implication of such a weighting procedure on the transport and sound absorbing properties of polydisperse fibrous media, highlighting their potential advantages. Furthermore, we discuss the challenges associated with this research field. Finally, we provide a brief perspective of the future directions and opportunities for advancing this area of study.

ABSTRACT Purpose: To evaluate the potential oncologic benefit of a visibly complete transurethral resection of a bladder tumor (TURBT) prior to neoadjuvant chemotherapy (NAC) and radical cystectomy (RC). Materials and Methods: We identified patients who received NAC and RC between 2011-2021. Records were reviewed to assess TURBT completeness. The primary outcome was pathologic downstaging (

The utility of currently available cortical prosthetic vision systems is disappointing. The essential features of a neuromorphic device that is predicted to enhance vision provided by available systems follow from a hypothesis which states that the objective and subjective aspects of cortical prosthetic vision jointly constitute patterns that emerge from specified synaptic interactions. The research reported here completes several required steps in developing an emulation of this device: (1) replication of small-scale simulations that are consistent with the hypothesis using the NEST (Écublens, Vaud, Switzerland) simulator, which can also be used for full-scale network emulation by a neuromorphic computer; (2) testing whether results consistent with the hypothesis survive increasing the scale and duration of simulations; (3) establishing a method that uses numbers of spikes produced by network neurons to report the number of phosphenes produced by cortical stimulation; and (4) simulating essential functions of a neuromorphic device which is predicted to enhance current prosthetic systems. NEST simulations replicated early results and increasing their scale and duration produced results consistent with the hypothesis. A decision function created using multinomial logistic regression correctly reported the expected number of phosphenes for three sets of 2080 spike number distributions in which half of each set arises from simulations expected to yield continuous visual forms by engaging a desired visual geometry. A process for modulating electrical stimulation amplitude based on intermittent population recordings that is predicted to produce desired visual geometries was successfully simulated. Implications of these results for future research are discussed.

Public health messaging in the United States during the COVID-19 pandemic has been variable in effectiveness. Different levels of governmental institutions have different goals and methods; it is unclear how messaging from these disparate levels is received, trusted, and implemented. We investigate the degrees of trust of Alaska Native and non-Alaska Native people in Southeast Alaska for the U.S. federal, Alaska state, and local Southeast Alaskan governments to parse how Southeast Alaskans feel about relative preparation, actions, and public health messaging. We use data collected in two waves of a regional survey: the first in April-June 2020, and the second in November 2020-February 2021. Results indicate that trust in the federal government was significantly lower than in the Alaska state government for each time period, and trust in both federal and state government significantly decreased between the two periods. Trust in the local governments of Southeast Alaska were significantly higher than both state and federal levels, and increased between the two survey waves, albeit insignificantly. We discuss potential drivers of these observations and outline how this can be leveraged for more comprehensive research into how relatively small communities with a large Native presence perceive public health messaging from different sources.

Summary: Atypical regulation of inflammation has been proposed in the etiology of autism spectrum disorder (ASD); however, measuring the temporal profile of fetal inflammation associated with future ASD diagnosis has not been possible. Here, we present a method to generate approximately daily profiles of prenatal and early childhood inflammation as measured by developmentally archived C-reactive protein (CRP) in incremental layers of deciduous tooth dentin. In our discovery population, a group of Swedish twins, we found heightened inflammation in the third trimester in children with future ASD diagnosis relative to controls (n = 66; 14 ASD cases; critical window: −90 to −50 days before birth). In our replication study, in the US, we observed a similar increase in CRP in ASD cases during the third trimester (n = 47; 23 ASD cases; −128 to −21 days before birth). Our results indicate that the third trimester is a critical period of atypical fetal inflammatory regulation in ASD.

ABSTRACT: Objectives: To describe the characteristics of nosocomial cases of Ebola virus disease (EVD) in the Democratic Republic of the Congo between July 2018 and May 2020 in order to inform future interventions. Methods: Nosocomial cases of EVD were identified during outbreak response surveillance, and a retrospective analysis of cases was conducted according to demographic characteristics and type of health facility (HF). Results: Of 3481 cases of EVD, 579 (16.6%) were nosocomial. Of these, 332 cases occurred in women (57.3%). Patients and visitors accounted for 419 cases (72.4%), of which 79 (18.9%) were aged 6–≤18 years and 108 (25.8%) were aged ≤5 years. Health workers (HWs) accounted for the remaining 160 (27.6%) nosocomial cases. The case fatality rate (CFR) for HWs (66/160, 41.3%) was significantly lower than the CFR for patients and visitors (292/419, 69.7%) (P39 beds) had the highest prevalence of nosocomial EVD (148/579, 25.6%). Among HFs with at least one case of nosocomial infection, 50.0% (98/196) were privately owned. Conclusions: Nurses and traditional healers should be targeted for infection prevention and control training, and supportive supervision should be provided to HFs to mitigate EVD transmission.

Elevated policy uncertainty acts as a tax on investment. In 1921, Frank Knight made a basic conceptual distinction between risk and uncertainty. In a market context, risks can be hedged through the use of different instruments, yet in the policy context, uncertainty makes waiting and seeing an option with value. However, this can come at a high economic cost. The academic analysis of policy uncertainty is today an active field of research globally. Some papers have been published in this regard, each using different approaches to measure macroeconomic and policy uncertainty. In 2015, the North-West University Business School (in conjunction with the School of Economics) pioneered the creation and publication of a Policy Uncertainty Index (PUI) for South Africa, which has since then captured the impact of key events – from ‘Nenegate’ to ‘Ramaphoria’. This paper presents an analysis of policy uncertainty in South Africa and how the PUI has contributed to an understanding of the economic environment in which business operates, with a specific focus on investment. The paper’s contribution lies in the unique context that it creates – where policymaking is more performative than evidence-based and there is a perennial tug of war between the state and market forces, against the backdrop of South Africa’s mixed economy.

Candida albicans and Staphylococcus aureus account for most invasive fungal and bacterial bloodstream infections (BSIs), respectively. However, the initial point of invasion responsible for S. aureus BSIs is often unclear. Recently, C. albicans has been proposed to mediate S. aureus invasion of immunocompromised hosts during co-colonization of oral mucosal surfaces. The status of the oral immune system crucially contributes to this process in two distinct ways: firstly, by allowing invasive C. albicans growth during dysfunction of extra-epithelial immunity, and secondly following invasion by some remaining function of intra-epithelial immunity. Immunocompromised individuals at risk of developing invasive oral C. albicans infections could, therefore, also be at risk of contracting concordant S. aureus BSIs. Considering the crucial contribution of both oral immune function and dysfunction, the aim of this review is to provide an overview of relevant aspects of intra and extra-epithelial oral immunity and discuss predominant immune deficiencies expected to facilitate C. albicans induced S. aureus BSIs.

At the end of the 2013–2016 Ebola virus disease outbreak in Guinea, we implemented an alert system for early detection of Ebola resurgence among survivors. Survivors were asked to report health alerts in their household and provide body fluid specimens for laboratory testing. During April–September 2016, a total of 1,075 (88%) of 1,215 survivors participated in the system; follow up occurred at a median of 16 months after discharge (interquartile range 14–18 months). Of these, 784 acted as focal points and reported 1,136 alerts (including 4 deaths among survivors). A total of 372 (91%) of 408 eligible survivors had >1 semen specimen tested; of 817 semen specimens, 5 samples from 4 survivors were positive up to 512 days after discharge. No lochia (0/7) or breast milk (0/69) specimens tested positive. Our findings underscore the importance of long-term monitoring of survivors’ semen samples in an Ebola-affected country.

Biomarker directed selection of targeted anti-neoplastic agents such as immune checkpoint inhibitors, small molecule inhibitors and monoclonal antibodies form an important aspect of cancer treatment. Immunohistochemistry (IHC) analysis of the tumor tissue is the method of choice to evaluate the presence of these biomarkers. However, a significant barrier to biomarker testing on tissue is the availability of an adequate amount of tissue and need for repetitive sampling due to tumor evolution. Also, tumor tissue testing is not immune to inter- and intra-tumor heterogeneity. We describe the analytical and clinical validation of a Circulating Tumor Cell (CTC) assay to accurately assess the presence of PD-L1 22C3 and PD-L1 28.8, ER, PR and HER2, from patients with solid tumors to guide the choice of suitable targeted therapies. Analytically, the test has high sensitivity, specificity, linearity and precision. Based on a blinded case control study, the clinical sensitivity and specificity for PD-L1 (22C3 and 28.8) was determined to be 90% and 100% respectively. The clinical sensitivity and specificity was 83% and 89% for ER; 80% and 94% for PR; 63% and 89% for HER2 (by ICC); and 100% and 92% for HER2 (by FISH), respectively. The performance characteristics of the test support its suitability and adaptability for routine clinical use.

Abstract Introduction Dementia severity can be empirically described by the latent dementia phenotype “δ” and its various composite “homologs”. We have explored δ's blood‐based protein biomarkers in the Texas Alzheimer's Research and Care Consortium (TARCC) study. However, it would be convenient to replicate those associations in the Alzheimer's Disease Neuroimaging Initiative (ADNI). To this end, we recently engineered a δ homolog from observed cognitive performance measures common to both projects (i.e., “dT2A”). Methods We used nine rationally chosen peripheral blood‐based protein biomarkers as indicators of a latent variable “INFLAMMATION”. We then associated that construct with dT2A in structural equation models adjusted for age, gender, depressive symptoms, and apolipoprotein E (APOE) ε4 allelic burden. Significant factor loadings and INFLAMMATION's association with dT2A were confirmed in random splits of TARCC's relatively large sample, and across biofluids in the ADNI. Results Nine proteins measured in serum (TARCC) or plasma (ADNI) explained ≅10% of dT2A's variance in both samples, independently of age, APOE, education, and gender. All loaded significantly on INFLAMMATION, and positively or negatively, depending on their known roles are PRO‐ or ANTI‐inflammatory proteins, respectively. The parameters of interest were confirmed across random 50% splits of the TARCC's sample, and replicated across biofluids in the ADNI. Discussion These results suggest that SEM can be used to replicate biomarker findings across samples and biofluids, and that a substantial fraction of dementia's variance is attributable to peripheral blood‐based protein levels.

The determination of endangered species is problematic. If one considers a species to be ontological individuals, then if a species goes extinct, it is gone forever. The Brook Trout is used as an example of a “species” which may be comprised of several unique entities that warrant a specific status. In addition to determining the specific status, it is difficult to determine how to place a monetary value on endangered species that do not have a general appeal to the public (e.g., many bird species), a commercial value, no known medical properties (e.g., deep water sponges vs. cancer), or generate monies for recreation. Perhaps if we could identify the unique information carried by a particular species, we could place a value on that information and assess the monetary value of the information lost.

In forensic DNA casework software tools aid in the data management and efficient, with low risk for error, interpretation and comparison of DNA profiling data. The need for such software has grown with increased numbers of genetic markers, more sensitive analysis methods and growing numbers of crime scene samples send for DNA analysis. To that end, the DNA eXpert System, DNAxs, was developed. This study describes how the expert system was realized and how it evolved during the first three years after the initial implementation. Insight is given in the software architecture, its modular design enabling to communicate with various software systems and how this system was implemented in a casework setting. The importance of quality aspects are highlighted, such as (automated) software testing at various levels. The code coverage is presented as well as the numbers of software bugs that were discovered. These bugs were more severe in earlier software versions than in the more recent versions and did not affect the interpretation of DNA results. The usefulness of the overall software suite and automated steps in DNA profile interpretation were evaluated based on its usage in forensic DNA casework during the first three years after its implementation at the developing laboratory. Because of automated profile comparisons, cases with larger numbers of profiles can be handled, are less prone to error and are extremely less time consuming. The implementation of an integrated quantitative probabilistic genotyping module into DNAxs enabled a more efficient workflow as no longer data files have to be exported and imported into different software. Extensive automated software tests and an audit trail serve as quality aspects for the usage of DNAxs. In times of the pandemic this software was found even more valuable than ever thought as it enabled working from home and it proved robust when used with many simultaneous users. The DNAxs software is regarded future proof and many new features and applications are envisioned.

Two networks are said to be linearly conjugate if the solution of their dynamic equations can be transformed into each other by a positive linear transformation. The study on dynamical equivalence in chemical kinetic systems was initiated by Craciun and Pantea in 2008 and eventually led to the Johnston-Siegel Criterion for linear conjugacy (JSC). Several studies have applied Mixed Integer Linear Programming (MILP) approach to generate linear conjugates of MAK (mass action kinetic) systems, Bio-CRNs (which is a subset of Hill-type kinetic systems when the network is restricted to digraphs), and PL-RDK (complex factorizable power law kinetic) systems. In this study, we present a general computational solution to construct linear conjugates of any "rate constant-interaction function decomposable" (RID) chemical kinetic systems, wherein each of its rate function is the product of a rate constant and an interaction function. We generate an extension of the JSC to the complex factorizable (CF) subset of RID kinetic systems and show that any non-complex factorizable (NF) RID kinetic system can be dynamically equivalent to a CF system via transformation. We show that linear conjugacy can be generated for any RID kinetic systems by applying the JSC to any NF kinetic system that are transformed to CF kinetic system.

Abstract Background Infectious disease prevention and control strategies require a coordinated, transnational approach. To establish core capacities of the International Health Regulations (IHR), the World Health Organization (WHO) developed the Integrated Diseases Surveillance and Response (IDSR) strategy. Epidemic-prone Lassa fever, caused by Lassa virus, is an endemic disease in the West African countries of Ghana, Guinea, Mali, Benin, Liberia, Sierra Leone, Togo and Nigeria. It’s one of the major public health threats in these countries. Here it is reported an epidemiological investigation of a cross-border case of Lassa fever, which demonstrated the importance of strengthened capacities of IHR and IDSR. Case presentation On January 9th, 2018 a 35-year-old Guinean woman with fever, neck pain, body pain, and vomiting went to a hospital in Ganta, Liberia. Over the course of her illness, the case visited various health care facilities in both Liberia and Guinea. A sample collected on January 10th was tested positive for Lassa virus by RT-PCR in a Liberian laboratory. The Guinean Ministry of Health (MoH) was officially informed by WHO Country Office for Guinea and for Liberia. Conclusion This case report revealed how an epidemic-prone disease such as Lassa fever can rapidly spread across land borders and how such threat can be quickly controlled with communication and collaboration within the IHR framework.

Background: Activation of the mTOR signaling pathway is ubiquitous in cancers and a favourable therapeutic target. However, presently approved mTOR inhibitor monotherapies have modest benefits in labeled indications while poor outcomes have been reported for mTOR inhibitor monotherapy when administered in a label-agnostic setting based on univariate molecular indications. The present study aimed to determine whether patient-specific combination regimens with mTOR inhibitors and other anticancer agents selected based on multi-analyte molecular and functional tumor interrogation (ETA: Encyclopedic Tumor Analysis) yields significant treatment response and survival benefits in advanced or refractory solid organ cancers.Methods: We evaluated treatment outcomes in 49 patients diagnosed with unresectable or metastatic solid organ cancers, of whom 3 were therapy naïve and 46 were pre-treated in whom the cancer had progressed on 2 or more prior systemic lines. All patients received mTOR inhibitor in combination with other targeted, endocrine or cytotoxic agents as guided by ETA. Patients were followed-up to determine Objective Response Rate (ORR), Progression Free Survival (PFS) and Overall Survival (OS).Results: The Objective Response Rate (ORR) was 57.1%, the disease Control rate (DCR) was 91.8%, median Progression Free Survival (mPFS) was 4.9 months and median Overall Survival (mOS) was 9.4 months. There were no Grade IV treatment related adverse events (AEs) or any treatment related deaths.Conclusion: Patient-specific combination regimens with mTOR inhibition and other anti-neoplastic agents, when selected based on multi-analyte molecular and functional profiling of the tumor can yield meaningful outcomes in advanced or refractory solid organ cancers.Trial Registration: Details of all trials are available at WHO-ICTRP: https://apps.who.int/trialsearch/. RESILIENT ID CTRI/2018/02/011808. ACTPRO ID CTRI/2018/05/014178. LIQUID IMPACT ID CTRI/2019/02/017548.

Abstract Introduction Mexican Americans remain severely underrepresented in Alzheimer's disease (AD) research. The Health & Aging Brain among Latino Elders (HABLE) study was created to fill important gaps in the existing literature. Methods Community‐dwelling Mexican Americans and non‐Hispanic White adults and elders (age 50 and above) were recruited. All participants underwent comprehensive assessments including an interview, functional exam, clinical labs, informant interview, neuropsychological testing, and 3T magnetic resonance imaging (MRI) of the brain. Amyloid and tau positron emission tomography (PET) scans were added at visit 2. Blood samples were stored in the Biorepository. Results Data was examined from n = 1705 participants. Significant group differences were found in medical, demographic, and sociocultural factors. Cerebral amyloid and neurodegeneration imaging markers were significantly different between Mexican Americans and non‐Hispanic Whites. Discussion The current data provide strong support for continued investigations that examine the risk factors for and biomarkers of AD among diverse populations.

Introduction Formulating written patient assessments requires the student to synthesize subjective and objective information and use clinical reasoning to reach a diagnosis. Medical students lack this skill, and clinical experience is not enough to acquire it. This session provides a structured process for learning how to formulate a patient assessment. Methods Third-year medical students participated in a large-group interactive skill session at the beginning of their pediatrics clerkship. Instructors following a scripted model walked students through practice examples to ultimately formulate a complete written patient assessment. The session covered data synthesis, use of appropriate medical terminology, and differential diagnosis development. Students used an audience response system to practice these skills. Results Over 1 academic year, 250 medical students participated in six sessions, with an average of 40–50 attendees per session. Over 90% of students completed pre- and postsession written patient assessments. These assessments were evaluated using portions of the Pediatric History and Physical Exam Evaluation grading rubric. The session had a positive effect on patient assessment formulation skills, with a significant increase in scores after the session. Discussion The session improved students' skill in generating more complete written patient assessments. Almost all students found the session valuable regardless of prior clinical experience. Nearly 50% of students felt inadequately prepared to formulate a written patient assessment prior to the session, revealing a skills gap for learners and a curricular teaching gap. This skill session provided a structured method and active learning format for teaching this essential clinical skill.

The long circulating half-life and inherently bivalent architecture of IgGs provide an ideal vehicle for presenting otherwise short-lived G-protein-coupled receptor agonists in a format that enables avidity-driven enhancement of potency. Here, we describe the site-specific conjugation of a dual agonist peptide (an oxyntomodulin variant engineered for potency and in vivo stability) to the complementarity-determining regions (CDRs) of an immunologically silent IgG4. A cysteine-containing heavy chain CDR3 variant was identified that provided clean conjugation to a bromoacetylated peptide without interference from any of the endogenous mAb cysteine residues. The resulting mAb-peptide homodimer has high potency at both target receptors (glucagon receptor, GCGR, and glucagon-like peptide 1 receptor, GLP-1R) driven by an increase in receptor avidity provided by the spatially defined presentation of the peptides. Interestingly, the avidity effects are different at the two target receptors. A single dose of the long-acting peptide conjugate robustly inhibited food intake and decreased body weight in insulin resistant diet-induced obese mice, in addition to ameliorating glucose intolerance. Inhibition of food intake and decrease in body weight was also seen in overweight cynomolgus monkeys. The weight loss resulting from dosing with the bivalently conjugated dual agonist was significantly greater than for the monomeric analog, clearly demonstrating translation of the measured in vitro avidity to in vivo pharmacology.

Objective: Diabetes is known to be associated with chronic kidney disease (CKD) and cardiovascular disease (CVD) independently. Type 2 cardiorenal syndrome (CRS), a recently defined syndrome, is characterized by primary renal failure that progressively leads to cardiac dysfunction. The effect of diabetes on cardiorenal syndrome has not been explored in a multi-ethnic population. In this retrospective secondary analysis, the hypothesis that diabetes modifies the effect of CVD on CKD was tested. Methods: The National Health and Nutrition Examination Survey (NHANES) is a cross-sectional survey that was performed on the non-institutionalized population in the United States. All patients from the NHANES study, who were 20 years and older between the years 1999 and 2010, were included in the analysis. CKD was determined using the Cockcroft-Gault equation. The analysis was performed using a complex samples logistic regression to determine the relationship between diabetes and CRS. Results: The prevalence of CKD among the population was 9.6% in Non-Hispanic Whites, 8.9% in African-Americans, and 4.5% in Hispanics. The overall unadjusted odds ratio for CKD to no CKD was 6.89 (95% confidence interval [CI], 6.13–7.75, p

The psychology of religion used to be a small and little known field. Although a few pockets of work in the area were done when Psychology began, it was functionally nonexistent for 1/3 of psychology’s history, and received little attention for most of the rest of it. However, in the past 20 years the field has become vast in scope. It now intersects all subfields of general psychology. Also, the psychology of religion no longer exists only in Western countries. It is now an international field with research being conducted worldwide. This article summarizes this trend and documents psychology of religion in the world and in Brazil as a part of it. The need for a multilevel interdisciplinary approach to research and theory is highlighted, as a way to synthesize knowledge of religiousness cross-culturally and trans-religiously. Future research should invoke a meaningmaking model in order to examine not merely observable religious behaviors, beliefs, or experiences, but their underlying roots, i.e., their meanings and attributions made about them. Such research can help us eliminate barriers between disciplines, cultures, religions, and nations.

Abstract Background By the end of the 2013–2016 West African Ebola Virus Disease (EVD) outbreaks, a total of 3814 cases (probable and confirmed) and 2544 deaths were reported in Guinea. Clearly, surveillance activities aiming at stopping human-to-human transmission have been the breakthrough of EVD outbreak management, but their application has been at times easier said than done. This article presents five confirmed or probable EVD cases that arose in Conakry towards the end of the Guinea epidemic, which demonstrate flaws in surveillance and follow-up. Case presentation For case 1, safe burial requirements were not followed. For cases 1 and 2, negative Polymerase Chain Reaction (PCR) results were interpreted as no infection. For the first case, the sample may have not been taken properly while for the second the disease was possibly at its early stage. Case 3 was stopped at a border health checkpoint and despite her high temperature she was allowed to continue the bus journey. For case 4, an oral swab sample was supposedly taken after death but could not be found for retrospective testing. Despite characteristic symptomatology, case 5 was not identified as a suspect case for as long as 3 weeks. Conclusion In epidemic contexts, health systems must be able to track all samples of suspect cases and deaths, regardless of their laboratory results. Social mobilization in communities and training in health care facilities must be strengthened at the tail of an outbreak, to avoid the natural slackening of disease surveillance, in particular for long-lasting and deadly epidemics.

Abstract Background Oculodentodigital dysplasia (ODDD) is a rare disorder with pleiotropic effects involving multiple body systems, caused by mutations in the gap junction protein alpha 1 (GJA1) gene. GJA1 gene encodes a polytopic connexin membrane protein, Cx43, that is a component of connexon membrane channels. Methods We describe two unrelated female probands referred for a genetic review in view of a dysmorphic clinical phenotype. Results Two novel missense mutations in GJA1 that substitute conserved amino acids in the first and second transmembrane domains (NM_000165.5: c.77T>C p.Leu26Pro and NM_000165.5:c.287T>G p.Val96Gly) were detected through targeted sequencing of GJA1. These variants were detected in the heterozygous state in the two Maltese probands and segregated with the disease phenotype. Conclusion This report further expands the mutational spectrum of ODDD.

Background Elbow deformity in children due to neglected proper fracture management is a devastating condition. The stiffness and pain complicated the function in daily activity. Successful management of neglected elbow dislocation is a challenging problem for orthopedic surgeons. In this study, we aimed to evaluate results of open reduction for neglected elbow dislocation in children. Case Description This is a case series of 13-14 years old neglected elbow dislocations, for up to 15 months. Open reduction after external distractor and followed by intensive rehabilitation was implemented. Clinical and functional outcome were evaluated within 4-7 years. Initial average elbow flexion was 53,3°, extension was 0°, arc of flexion was 53,3°, arc of pronation-supination was 150° and Mayo Elbow Performance Index (MEPI) was 80. Clinical and functional outcome were evaluated within 4-7 years. At follow-up after open reduction, the improvement in whole range of movement was significant. Average elbow flexion was 118,3°, extension was 36,67°, arc of flexion was 81,67°, arc of pronation-supination was 133°. The average improvement of flexion was 65°, arc of flexion was 31,67°, and arc of pronation-supination was 8,3°. The average loss of flexion was 15,5%, arc of flexion was 44,2%, and arc of pronation-supination was 10,7% compared with uninjured side. The average Mayo Elbow Performance Index (MEPI) was 96,67; all with excellent results. Conclusion Planned and well execution open reduction in pediatric neglected elbow dislocation may bring back the painless movement within normal daily function.

Purpose: Atrial fibrillation (AF) is the most common arrhythmia treated in the world. While medical treatment with antiarrhythmic drugs remains the primary treatment modality, symptomatic refractory AF often requires treatment with a catheter or surgical ablation. One minimally invasive therapy is the Mini-Maze procedure, which utilizes epicardial radiofrequency ablation via a subxiphoid approach to rid the heart of arrhythmogenic atrial foci without a median sternotomy or cardiopulmonary bypass. The goal of this retrospective cohort study was to identify clinical factors associated with metabolic acidosis following the Mini-Maze procedure. Materials and Methods: After Institutional Review Board approval, we studied patients undergoing the Mini-Maze procedure, off-pump coronary artery bypass grafting or patients conventional Cox-Maze on cardiopulmonary bypass. The first base deficit value obtained in the Intensive Care Unit was used as a measure of metabolic acidosis. Using logistic regression with Akaike information criteria, we analyzed preoperative, intraoperative, and postoperative data to determine the factors associated with changes in base deficit. Results: A multivariable model using stepwise selection demonstrated that diabetes mellitus and weight were associated with a decrease in the base deficit by 2.87 mEq/L (95% CI: −5.55-−0.19) and 0.04 mEq/L (95%CI: −0.08, 0.004), respectively. Furthermore, creatinine was associated with a 1.57 mEq/L (95% CI: 0.14, 2.99) increase in the base deficit. Conclusion: The Mini-Maze procedure was not associated with postoperative metabolic acidosis. Instead, nondiabetic patients and patients with higher creatinine were associated with greater base deficits after undergoing cardiac surgery.

Summary: Background: Treatment of latent yaws is a crucial component of the WHO yaws eradication strategy to prevent relapse and the resulting transmission to uninfected children. We assessed the effectiveness of single-dose azithromycin to treat patients with latent yaws. Methods: This population-based cohort study included children (age

Activation of G protein-coupled receptors (GPCRs) by agonist ligands is mediated by a transition from an inactive to active receptor conformation. We describe a novel single-molecule assay that monitors activation-linked conformational transitions in individual GPCR molecules in real-time. The receptor is site-specifically labeled with a Cy3 fluorescence probe at the end of trans-membrane helix 6 and reconstituted in phospholipid nanodiscs tethered to a microscope slide. Individual receptor molecules are then monitored over time by single-molecule total internal reflection fluorescence microscopy, revealing spontaneous transitions between inactive and active-like conformations. The assay provides information on the equilibrium distribution of inactive and active receptor conformations and the rate constants for conformational exchange. The experiments can be performed in the absence of ligands, revealing the spontaneous conformational transitions responsible for basal signaling activity, or in the presence of agonist or inverse agonist ligands, revealing how the ligands alter the dynamics of the receptor to either stimulate or repress signaling activity. The resulting mechanistic information is useful for the design of improved GPCR-targeting drugs. The single-molecule assay is described in the context of the β2 adrenergic receptor, but can be extended to a variety of GPCRs.

BACKGROUND:Haemophilus ducreyi and Treponema pallidum subsp. pertenue are major causes of leg ulcers in children in Africa and the Pacific Region. We investigated the presence of DNA (PCR positivity) from these bacteria on asymptomatic people, flies, and household linens in an endemic setting. METHODOLOGY/PRINCIPAL FINDINGS:We performed a cross-sectional study in rural villages of Lihir Island, Papua New Guinea during a yaws elimination campaign. Participants were asymptomatic subjects recruited from households with cases of leg ulcers, and from households without cases of leg ulcers. We rubbed swabs on the intact skin of the leg of asymptomatic individuals, and collected flies and swabs of environmental surfaces. All specimens were tested by PCR for H. ducreyi and T. p. pertenue DNA. Of 78 asymptomatic participants that had an adequate specimen for DNA detection, H. ducreyi-PCR positivity was identified in 16 (21%) and T. p. pertenue-PCR positivity in 1 (1%). In subgroup analyses, H. ducreyi-PCR positivity did not differ in participants exposed or not exposed to a case of H. ducreyi ulcer in the household (24% vs 18%; p = 0.76). Of 17 cultures obtained from asymptomatic participants, 2 (12%) yielded a definitive diagnosis of H. ducreyi, proving skin colonization. Of 10 flies tested, 9 (90%) had H. ducreyi DNA and 5 (50%) had T. p. pertenue DNA. Of 6 bed sheets sampled, 2 (33%) had H. ducreyi DNA and 1 (17%) had T. p. pertenue DNA. CONCLUSIONS/SIGNIFICANCE:This is the first time that H. ducreyi DNA and colonization has been demonstrated on the skin of asymptomatic children and that H. ducreyi DNA and T. p. pertenue DNA has been identified in flies and on fomites. The ubiquity of H. ducreyi in the environment is a contributing factor to the spread of the organism.

To estimate failure rates after treatment with benzathine penicillin and to identify determinants of failure that affected outcomes for yaws, we conducted a cohort study of 138 patients; treatment failed in 24 (17.4%). Having low initial titers on Venereal Disease Research Laboratory test and living in a village where yaws baseline incidence was high were associated with increased likelihood of treatment failure.

Background: To eradicate yaws, national control programmes use the Morges strategy (initial mass treatment and biannual resurveys). The resurvey component is designed to actively detect and treat remaining yaws cases and is initiated on the basis of laboratory-supported reactive non-treponemal serology (using the rapid plasma reagin [RPR] test). Unfortunately, the RPR test is available rarely in yaws-endemic areas. We sought to assess a new point-of-care assay—the Dual Path Platform (DPP) syphilis assay, which is based on simultaneous detection of antibodies to treponemal and non-treponemal antigens—for guiding use of antibiotics for yaws eradication. A secondary goal was to ascertain at what timepoint the DPP assay line reverted to negative after treatment. Methods: 703 children (aged 1–18 years) with suspected clinical yaws living in two remote, yaws-endemic villages in Papua New Guinea were enrolled. Clinical suspicion of yaws was established according to a WHO pictorial guide. We obtained blood samples from all patients. We calculated the sensitivity and specificity of the DPP assay for detection of antibodies to treponemal (T1) and non-treponemal (T2) antigens and compared values against those obtained with standard laboratory tests (the Treponema pallidum haemagglutination assay [TPHA] and the RPR test). We followed up a subsample of children with dually positive serology (T1 and T2) to monitor changes in DPP optical density (using an automatic reader) at 3 and 6 months. This trial is registered with ClinicalTrials.gov, number NCT01841203. Findings: Of 703 participants, 389 (55%) were reactive for TPHA, 305 (43%) for the RPR test, and 287 (41%) for both TPHA and the RPR test. The DPP T1 (treponemal) assay had a sensitivity of 88·4% (95% CI 84·8–91·4) and specificity of 95·2% (92·2–97·3). The DPP T2 (non-treponemal) assay had a sensitivity of 87·9% (83·7–91·3) and specificity of 92·5% (89·4–94·9). In subgroup analyses, sensitivities and specificities did not differ according to type of specimen (plasma vs whole blood). For specimens with an RPR titre of 1:8 or greater, the sensitivity of the DPP T2 assay was 94·1% (95% CI 89·9–96·9). Serological cure (including seroreversion or a fourfold reduction in optical density value) was attained at 6 months in 173 (95%) of 182 children with dual-positive serology. Interpretation: The DPP assay is accurate for identification of antibodies to treponemal and non-treponemal antigens in patients with yaws and avoids the need for laboratory support. A change of diagnostic procedure from the currently implemented RPR test to the simpler DPP assay could ease the implementation of yaws eradication activities. Funding: Chembio Diagnostic Systems, Newcrest Mining, and the Papua New Guinea National Department of Health.

Geschwind syndrome has been described in patients with temporal lobe epilepsy and is characterized by sexual behavioural disorders, hyperreligiosity, hypergraphia, and viscosity. Presented here is a case of a 53-year-old man with clinical findings consistent with Geschwind syndrome in the setting of a known diagnosis of schizoaffective disorder, with no identifiable comorbid illness of temporal lobe epilepsy or frontotemporal dementia. Brain MRI showed bilateral temporal lobe atrophy greater than would be expected for age and more prominent on the left side than the right. It is likely that these structural abnormalities may be related to this patient’s clinical presentation of Geschwind syndrome. To our knowledge, this is the first reporting of a case of Geschwind syndrome in the setting of schizoaffective disorder. These symptoms of Geschwind syndrome were present irrespective of mental state status. The report highlights the importance in correct identification of underlying cause and differentiation between Geschwind syndrome and schizoaffective disorder in order to avoid mistreatment and consequent iatrogenic adverse events.

BACKGROUND:Annual mass drug administration (MDA) over five years is the WHO's recommended strategy to eliminate lymphatic filariasis (LF). Some experts, however, consider that longer periods of treatment might be necessary in certain high prevalence and transmission environments based upon past unsuccessful field experience and modelling. METHODOLOGY/PRINCIPAL FINDINGS:To evaluate predictors of success in a LF control program we conducted an ecological study during a pre-existing MDA program. We studied 27 villages in Lihir Island, Papua New Guinea, from two areas with different infection rates before MDA. We undertook surveys to collect information on variables potentially having an influence on the outcome of the program, including epidemiological (baseline prevalence of infection, immigration rate), entomological (vector density) and operational (treatment coverage, vector control strategies) variables. The success in a village was defined using variables related to the infection (circulating filarial antigenemia prevalence < 1%) and transmission (antigenemia prevalence < 1 in 1000 children born since start of MDA). 8709 people were involved in the MDA program and average coverage rates were around 70%. The overall prevalence of filariasis fell from an initial 17.91% to 3.76% at round 5 (p < 0.001). Viewed on a village by village basis, 12/27 (44%) villages achieved success. In multivariate analysis, low baseline prevalence was the only factor predicting both success in reducing infection rates (OR 19,26; CI 95% 1,12 to 331,82) and success in preventing new infections (OR 27,44; CI 95% 1,05 to 719,6). Low vector density and the use of an optimal vector control strategy were also associated with success in reducing infection rates, but this did not reach statistical significance. CONCLUSIONS/SIGNIFICANCE:Our results provide the data that supports the recommendation that high endemic areas may require longer duration MDA programs, or alternative control strategies.

Three-phase, horizontal, gravity separation vessels are the principal method of extracting oil and gas from unwanted produced water and solids prior to transportation. Traditionally, oil production separators have used separate single-point transmitters for interface and bulk level measurement. This paper shows how a profile of the different layers as opposed to single-point measurement can enable oil production and chemical usage to be optimised.

Abstract Background The zebrafish retina maintains two populations of stem cells: first, the germinal zone or ciliary marginal zone (CMZ) contains multipotent retinal progenitors that add cells to the retinal periphery as the fish continue to grow; second, radial glia (Müller cells) occasionally divide asymmetrically to generate committed progenitors that differentiate into rod photoreceptors, which are added interstitially throughout the retina with growth. Retinal injury stimulates Müller glia to dedifferentiate, re-enter the cell cycle, and generate multipotent retinal progenitors similar to those in the CMZ to replace missing neurons. The specific signals that maintain these two distinct populations of endogenous retinal stem cells are not understood. Results We used genetic and pharmacological manipulation of the β-catenin/Wnt signaling pathway to show that it is required to maintain proliferation in the CMZ and that hyperstimulation of β-catenin/Wnt signaling inhibits normal retinal differentiation and expands the population of proliferative retinal progenitors. To test whether similar effects occur during regeneration, we developed a method for making rapid, selective photoreceptor ablations in larval zebrafish with intense light. We found that dephosphorylated β-catenin accumulates in Müller glia as they re-enter the cell cycle following injury, but not in Müller glia that remain quiescent. Activation of Wnt signaling is required for regenerative proliferation, and hyperstimulation results in loss of Müller glia from the INL as all proliferative cells move into the ONL. Conclusions β-catenin/Wnt signaling is thus required for the maintenance of retinal progenitors during both initial development and lesion-induced regeneration, and is sufficient to prevent differentiation of those progenitors and maintain them in a proliferative state. This suggests that the β-catenin/Wnt cascade is part of the shared molecular circuitry that maintains retinal stem cells for both homeostatic growth and epimorphic regeneration.

La estructura de hormigón armado que cubre el club en el hotel La Concha, de San Juan de Puerto Rico, tiene forma de concha ondulada elipsoidal. Se ha situado en un estanque poco profundo, del que emerge como si hubiese venido del océano que tiene delante.

Climate-sensitive northern cryosphere inland waters emit greenhouse gases (GHGs) into the atmosphere, yet their total emissions remain poorly constrained. We present a data-driven synthesis of GHG emissions from northern cryosphere inland waters considering water body types, cryosphere zones, and seasonality. We find that annual GHG emissions are dominated by carbon dioxide ([Formula: see text] teragrams of CO 2 ; [Formula: see text]) and methane ([Formula: see text] teragrams of CH 4 ), while the nitrous oxide emission ([Formula: see text] gigagrams of N 2 O) is minor. The annual CO 2 -equivalent (CO 2 e) GHG emissions from northern cryosphere inland waters total [Formula: see text] or [Formula: see text] petagrams of CO 2 e using the 100- or 20-year global warming potentials, respectively. Rivers emit 64% more CO 2 e GHGs than lakes, despite having only one-fifth of their surface area. The continuous permafrost zone contributed half of the inland water GHG emissions. Annual CO 2 e emissions from northern cryosphere inland waters exceed the region's terrestrial net ecosystem exchange, highlighting the important role of inland waters in the cryospheric land-aquatic continuum under a warming climate.

The study comprehensively evaluates low-cost CO 2 sensors from different price tiers, assessing their performance against a reference-grade instrument and exploring the possibility of calibration using different machine learning techniques. Three sensors (Sunrise AB by Senseair, K30 CO 2 by Senseair, and GMP 343 by Vaisala) were tested alongside a reference instrument (Los Gatos precision greenhouse gas analyzer). The results revealed differences in sensor performance, with the higher cost Vaisala sensors exhibiting superior accuracy. Despite its lower price, the Sunrise sensors still demonstrated reasonable accuracy. Meanwhile, the K30 sensor measurements displayed higher variability and noise. Machine learning models, including linear regression, gradient boosting regression, and random forest regression, were employed for sensor calibration. In general, linear regression models performed best for extrapolating data, whereas decision tree-based models were generally more useful in handling non-linear datasets. Notably, a stack ensemble model combining these techniques outperformed the individual models and significantly improved sensor accuracy by approximately 65%. Overall, this study contributes to filling the gap in intercomparing CO 2 sensors across different price categories and underscores the potential of machine learning for enhancing sensor accuracy, particularly in low-cost sensor applications.

Methane (CH 4 ) is a potent greenhouse gas and its concentrations have tripled in the atmosphere since the industrial revolution. There is evidence that global warming has increased CH 4 emissions from freshwater ecosystems 1,2 , providing positive feedback to the global climate. Yet for rivers and streams, the controls and the magnitude of CH 4 emissions remain highly uncertain 3,4 . Here we report a spatially explicit global estimate of CH 4 emissions from running waters, accounting for 27.9 (16.7-39.7) Tg CH 4  per year and roughly equal in magnitude to those of other freshwater systems 5,6 . Riverine CH 4 emissions are not strongly temperature dependent, with low average activation energy (E M  = 0.14 eV) compared with that of lakes and wetlands (E M  = 0.96 eV) 1 . By contrast, global patterns of emissions are characterized by large fluxes in high- and low-latitude settings as well as in human-dominated environments. These patterns are explained by edaphic and climate features that are linked to anoxia in and near fluvial habitats, including a high supply of organic matter and water saturation in hydrologically connected soils. Our results highlight the importance of land-water connections in regulating CH 4 supply to running waters, which is vulnerable not only to direct human modifications but also to several climate change responses on land., (© 2023. The Author(s).)

Arctic rivers provide an integrated signature of the changing landscape and transmit signals of change to the ocean. Here, we use a decade of particulate organic matter (POM) compositional data to deconvolute multiple allochthonous and autochthonous pan-Arctic and watershed-specific sources. Constraints from carbon-to-nitrogen ratios (C:N), δ 13 C, and Δ 14 C signatures reveal a large, hitherto overlooked contribution from aquatic biomass. Separation in Δ 14 C age is enhanced by splitting soil sources into shallow and deep pools (mean ± SD: -228 ± 211 vs. -492 ± 173‰) rather than traditional active layer and permafrost pools (-300 ± 236 vs. -441 ± 215‰) that do not represent permafrost-free Arctic regions. We estimate that 39 to 60% (5 to 95% credible interval) of the annual pan-Arctic POM flux (averaging 4,391 Gg/y particulate organic carbon from 2012 to 2019) comes from aquatic biomass. The remainder is sourced from yedoma, deep soils, shallow soils, petrogenic inputs, and fresh terrestrial production. Climate change-induced warming and increasing CO 2 concentrations may enhance both soil destabilization and Arctic river aquatic biomass production, increasing fluxes of POM to the ocean. Younger, autochthonous, and older soil-derived POM likely have different destinies (preferential microbial uptake and processing vs. significant sediment burial, respectively). A small (~7%) increase in aquatic biomass POM flux with warming would be equivalent to a ~30% increase in deep soil POM flux. There is a clear need to better quantify how the balance of endmember fluxes may shift with different ramifications for different endmembers and how this will impact the Arctic system.

SignificanceStream/river carbon dioxide (CO 2 ) emission has significant spatial and seasonal variations critical for understanding its macroecosystem controls and plumbing of the terrestrial carbon budget. We relied on direct fluvial CO 2 partial pressure measurements and seasonally varying gas transfer velocity and river network surface area estimates to resolve reach-level seasonal variations of the flux at the global scale. The percentage of terrestrial primary production (GPP) shunted into rivers that ultimately contributes to CO 2 evasion increases with discharge across regions, due to a stronger response in fluvial CO 2 evasion to discharge than GPP. This highlights the importance of hydrology, in particular water throughput, in terrestrial-fluvial carbon transfers and the need to account for this effect in plumbing the terrestrial carbon budget.