Degree Of Variability Research Articles

Pan-cancer analysis of tumor mutation burden and other key ICI biomarkers in the Indian cohort.

e18872 Background: Tumor Mutation Burden has been correlated with therapy outcomes in patients receiving immune checkpoint inhibitors (ICI). However, tumor specific TMB cut-offs are not well established in the Indian cohort. Genomic alterations are shown to be vital determinants of response, resistance, and hyper-progression post-ICI administration and information about these alterations in Indian patients is scarce. Further, there is limited evidence of reliable predictive biomarkers in ‘immunologically cold’ tumors representing a crucial challenge in this setting. Uncovering key molecular alterations along with TMB and other genomic signatures can aid in selecting potential candidates for immunotherapy. Methods: The study cohort comprised 1383 tumor tissue specimens from solid tumors across twenty three organs including the bladder, breast, lung, ovary, colon, stomach, esophagus, kidney, liver, pancreas, etc. Targeted next-generation sequencing was carried out for more than 400 genes. dMMR/MSI status was evaluated in a subset of samples. Results: Of the 1383 tumor samples analyzed, 81.6% showed TMB-Low ( < 10 mut/Mb), while 18.4% samples had TMB-High (≥10 mut/Mb) and 6.1% had TMB ≥16 mut/Mb. Bladder and cervical cancer sub-cohorts showed the highest median TMB of 8. Breast cancer was the largest subcohort comprising 255 samples with a median TMB of 5. The lowest median TMB of 4 was seen in thyroid cancer. Highest degree of variability was observed within cervical cancer subcohort with TMBs ranging from 1 – 39 mut/Mb, followed by thyroid (1 – 29 mut/Mb), prostate (2 – 31 mut/Mb), and breast (1 – 88 mut/Mb) subcohorts. The least variation in TMB was observed in tumors of the pancreaticobiliary tract (1- 12 m/Mb) and small intestine (3 – 12 m/Mb). Among TMB-H tumors, markers of potential hyper-progression were analyzed. MDM2 amplification (CNV ≥8 copies) was detected in 2.4% (6/254) and MYC amplification (CNV ≥6 copies) was detected in 7.1% (18/254) cases. In a breast cancer subcohort, PIK3CA mutation-linked immune-cold tumor microenvironment was detected in 36% of TMB-H tumors against 29% of TMB-L tumors. Only 0.8% (6/751) samples were diagnosed as MSI-H/dMMR, at a significantly lower incidence against the reported incidence in the western population. All 6 MSI-H patients were also TMB-H; while 95.9% (139/145) patients with TMB-H were found to be MSI-stable. Conclusions: This study gives insights into key ICI biomarkers with TMB profiles of Indian patients and reinforces the varied range of TMB depending on tumor type. The incidence of key genes involved in hyper-progression may support active disease monitoring on ICI therapy in such patients and co-application of multi-pathway therapies to address these resistant pathways. These findings suggest that wider prospective studies to establish cancer-specific thresholds concerning tumor type and patient outcomes should be undertaken.

P11: Mechanical Properties of the Common Bile Duct: Insights into Benign Biliary Structure Pathophysiology

Benign biliary strictures (BBS) that develop in the common bile duct (CBD) are often a result of postoperative or inflammatory processes. For instance, one-third of patients who undergo procedures such as cholecystectomy or liver transplants can develop surgery-related BBS. Current treatments for BBS are plagued by difficulties, complications, and failures, which result in high costs and risks associated with reinterventions. The failures may be due to a lack of knowledge about the structure of the CBD and the use of devices that are not designed for this specific application. This study aims to determine the mechanical properties of the CBD to better understand the pathophysiology of BBS, calibrate computational models, and the future evaluation of new treatment methods. Geometrical measurements and evaluations of the bile ducts (CBD, sphincter of Oddi, cystic, and common hepatic ducts) and the gallbladder were carried out on 31 adult pigs obtained from a local slaughterhouse. Pressurized diameter measurements were recorded at healthy and pathological pressures, and burst tests were performed on CBD sections (n=3). Longitudinal (lon, n=16) and circumferential (circ, n=25) tensile strength tests were performed on CBD sections at a rate of 50 mm/min until rupture, yielding the modulus of elasticity (E), ultimate strength, and fracture strengths. A creep test was performed in a bath at -4°C, with a weight of 3 g applied for 28 days. The test involved a 90° turn at day 14, with deformation monitored for 7 days without load (n=3). A high degree of variability was reported in bile duct size in terms of length (84.1 ± 17.5 mm) and relaxed diameter (6.2 ± 1.9 mm). The modulus of elasticity associated with elastin (0.111 ± 0.111 MPa) and collagen (4.744 ± 2.193 MPa) exceeded the circumferential values (0.019 ± 0.017 MPa and 2.850 ± 1.585 MPa, respectively). Lower results for the modulus of elasticity and higher dilation after the creep tests were observed in the proximal zone of the CBD near the duodenum (day 14: 41%, day 28: 43%, day 35: 67%), indicating lower stiffness. Additionally, all regions of the CBD retained most of their deformation even after 7 days in the absence of load. The data reported in this study provides valuable information on how the technique and treatment times can be improved in cases of BBS.

The effect of residual pellet volume on cryoprotectant concentration and post-thaw motility of stallion sperm

Standard protocols for cryopreservation of stallion sperm involve centrifugation to remove plasma and concentrate ejaculates. Typically, semen is diluted 1:1 or higher to a concentration of 50 to 100 × 106/ml and centrifuged on a cushion. Most supernatant and cushion is aspirated leaving 5-10% of the original volume of diluted semen along with the sperm pellet. Pellets are resuspended in freezing diluent containing cryoprotectant to 200 × 106 sperm/ml. Due to the extreme variability of sperm concentration between ejaculates, the volume of resuspended sperm pellet and supernatant may contribute significantly to the final volume of the extended semen resulting in variability in the final percent of cryoprotectant (CPA) in the extended semen. To determine the degree of variability and the effect of the final CPA concentration on retention of sperm motility we determined final CPA concentration in extended semen of 129 ejaculates from 16 different stallions. Our hypothesis was that ejaculates cryopreserved with CPA concentration significantly lower than that present in the freezing diluent would have lower cryosurvival. Pellet volume was determined by weight and used to calculate the final CPA concentration prior to freezing for each ejaculate. The final CPA concentration was expressed as percentage of the CPA concentration in the original freezing extender. For the 129 ejaculates, the mean final CPA concentration aspercentage of original was 69.5%, median 73.7%, min 39.2% and max 87.8%. Final CPA concentration 1.3 - 5.1%. Sperm motility was analyzed by CASA for fresh extended and post-thaw samples. Thawed samples were diluted in centrifugation media and incubated (37C for 30 minutes) prior to analysis. For each sample a minimum of 5 fields and 400 motile sperm were analyzed (40 frames at 60 frames/sec); progressive cells defined as (VAP > 50 mic/sec and STR > 75%). Cryosurvival was expressed as percentage change in motility between pre-freeze and post-thaw values. Ejaculates were divided into 5 groups based on final CPA concentration as percentage of the original extender amount (G1 = 40-50%, G2 = 50-60%, G3 = 60-70%, G4 = 70-80%, G5 = 80-90%). Mean values for change in motility were compared between groups using ANOVA with multiple comparisons. Decrease in percent total motility (mean,sd) was less (p<0.05) in G5 (22.8,11.0) compared to all other groups G4 (31.3,11.3), G3 (31.2,13.1), G2 (29.5,8.8), G1 (30.9,10.8). Decrease in progressive motility was less (p<0.05) in G4 (8.5,14.8) and G5 (2.7,10.5) vs G1(17.8,8.7), G5 vs G2 (13.6,10.9) and G5 vs G3 (12.9,14.3). These data suggest that current protocols for cryopreservation of stallion semen may result in inadequate CPA concentration in extended semen of many ejaculates. Further experiments are underway to determine critical thresholds.

Genetic Diversity and Population Structure of Leishmania infantum in Morocco as Revealed by Multilocus Sequence Typing (MLST) Approach.

Leishmania infantum is endemic in Morocco, and it causes both visceral (VL) and cutaneous leishmaniasis (CL). In this study, the multilocus sequence typing (MLST) approach was used to investigate the phylogeny and population structure of Leishmania infantum strains isolated from CL and VL patients and the canine reservoir in different leishmaniasis endemic foci in Morocco. For this purpose, eight loci (pgm, alat, me, fh, g6pd, pgd, gpi and cytb) were amplified in 40 samples, out of which 31 were successfully sequenced. The genetic diversity analysis detected a high degree of intraspecific genetic variability among the studied strains. The phylogenetic and the haplotype analyses showed that most of the strains from the same geographical areas clustered together. The recombination among Leishmania infantum strains was revealed through a splits tree analysis and the number of recombination events. Moreover, the assessment of the gene flow between Leishmania infantum and Leishmania tropica through phylogenetic analysis and haplotype diversity in two endemic foci where the two species were sympatric showed no genetic exchange between the two species.

Reference-free Bayesian model for pointing errors of typein neurosurgical planning.

Many neurosurgical planning tasks rely on identifying points of interest in volumetric images. Often, these points require significant expertise to identify correctly as, in some cases, they are not visible but instead inferred by the clinician. This leads to a high degree of variability between annotators selecting these points. In particular, errors of type are when the experts fundamentally select different points rather than the same point with some inaccuracy. This complicates research as their mean may not reflect any of the experts' intentions nor the ground truth. We present a regularised Bayesian model for measuring errors of type in pointing tasks. This model is reference-free; in that it does not require a priori knowledge of the ground truth point but instead works on the basis of the level of consensus between multiple annotators. We apply this model to simulated data and clinical data from transcranial magnetic stimulation for chronic pain. Our model estimates the probabilities of selecting the correct point in the range of 82.6[Formula: see text]88.6% with uncertainties in the range of 2.8[Formula: see text]4.0%. This agrees with the literature where ground truth points are known. The uncertainty has not previously been explored in the literature and gives an indication of the dataset's strength. Our reference-free Bayesian framework easily models errors of type in pointing tasks. It allows for clinical studies to be performed with a limited number of annotators where the ground truth is not immediately known, which can be applied widely for better understanding human errors in neurosurgical planning.

Mass-Spectrometric Evaluation of the African Swine Fever Virus-Induced Host Shutoff Using Dynamic Stable Isotope Labeling with Amino Acids in Cell Culture (SILAC).

African swine fever is a viral disease of swine caused by the African swine fever virus (ASFV). Currently, ASFV is spreading over the Eurasian continent and threatening global pig husbandry. One viral strategy to undermine an efficient host cell response is to establish a global shutoff of host protein synthesis. This shutoff has been observed in ASFV-infected cultured cells using two-dimensional electrophoresis combined with metabolic radioactive labeling. However, it remained unclear if this shutoff was selective for certain host proteins. Here, we characterized ASFV-induced shutoff in porcine macrophages by measurement of relative protein synthesis rates using a mass spectrometric approach based on stable isotope labeling with amino acids in cell culture (SILAC). The impact of ASFV infection on the synthesis of >2000 individual host proteins showed a high degree of variability, ranging from complete shutoff to a strong induction of proteins that are absent from naïve cells. GO-term enrichment analysis revealed that the most effective shutoff was observed for proteins related to RNA metabolism, while typical representatives of the innate immune system were strongly induced after infection. This experimental setup is suitable to quantify a virion-induced host shutoff (vhs) after infection with different viruses.

Superspreading, overdispersion and their implications in the SARS-CoV-2 (COVID-19) pandemic: a systematic review and meta-analysis of the literature

BackgroundA recurrent feature of infectious diseases is the observation that different individuals show different levels of secondary transmission. This inter-individual variation in transmission potential is often quantified by the dispersion parameter k. Low values of k indicate a high degree of variability and a greater probability of superspreading events. Understanding k for COVID-19 across contexts can assist policy makers prepare for future pandemics.MethodsA literature search following a systematic approach was carried out in PubMed, Embase, Web of Science, Cochrane Library, medRxiv, bioRxiv and arXiv to identify publications containing epidemiological findings on superspreading in COVID-19. Study characteristics, epidemiological data, including estimates for k and R0, and public health recommendations were extracted from relevant records.ResultsThe literature search yielded 28 peer-reviewed studies. The mean k estimates ranged from 0.04 to 2.97. Among the 28 studies, 93% reported mean k estimates lower than one, which is considered as marked heterogeneity in inter-individual transmission potential. Recommended control measures were specifically aimed at preventing superspreading events. The combination of forward and backward contact tracing, timely confirmation of cases, rapid case isolation, vaccination and preventive measures were suggested as important components to suppress superspreading.ConclusionsSuperspreading events were a major feature in the pandemic of SARS-CoV-2. On the one hand, this made outbreaks potentially more explosive but on the other hand also more responsive to public health interventions. Going forward, understanding k is critical for tailoring public health measures to high-risk groups and settings where superspreading events occur.

Horse serum or equine platelet lysate increases total vascular endothelial growth factor A concentrations and correlates with vascular growth in an equine facial arterial ring assay.

To evaluate ex vivo angiogenesis of equine arterial rings in response to various growth media. Facial arteries were dissected from 11 horses post-euthanasia. Equine platelet lysate (ePL) was harvested from 6 horses. Arteries were exposed to endothelial growth media (EGM) + horse serum (HS) for first sprout (FS), vascular regression (VR), and (basement membrane matrix [Matrigel]) lysis (ML) evaluation. Additional rings supplemented with (1) EGM, (2) EGM + EDTA, (3) endothelial basal media (EBM), (4) EBM + HS, or (5) EBM + human VEGF were compared for vascular network area (VNA) and maximum network growth (MNG). Additional rings exposed to EGM + ePL at 10-(10xePL), 5-(5xePL), or 2-fold (2xePL) increases from baseline platelet concentration, EGM + HS, EGM + platelet-poor plasma (PPP), EBM + PPP and EBM were analyzed for branch number, density, VNA, and VEGF-A concentration from days 0-3. Arteries demonstrated sprouting in Matrigel supplemented with EBM alone. EGM + HS exposure resulted in no differences in FS (P = .3934), VR (P = .0607), or ML (P = .2364) between horses. VNA in EGM + HS was greater than EBM (P = .0015). MNG was greater in EGM + HS, EBM + HS, and EBM + hVEGF compared with EBM (P = .0001). ePL treatment did not have an overall significant angiogenic effect compared with supplementation with HS, PPP, or EBM alone; however, VEGF-A concentrations were higher for EGM + 10xePL, EGM + 5xePL, and EGM-HS compared with EBM and positively correlated with VNA (P = .0243). Equine arterial rings serve as an ex vivo model for angiogenesis but have a high degree of variability. HS, PPP, or ePL support vascular growth, and HS and ePL may stimulate the secretion and be sources of VEGF-A.

Comparison of anaerobic speed reserve and maximal aerobic speed methods to prescribe short format high-intensity interval training.

The purpose of the study was to compare the degree of intersubject variability in the cardiorespiratory, metabolic, and perceptual responses to high-intensity interval training (HIIT) prescribed based on the relative anaerobic speed reserve (ASR) or maximal aerobic speed (MAS) and to identify the optimal % ASR for execution of such HIIT. Seventeen male physical education students (age: 23.6 ± 1.1 years, height: 180.2 ± 5.9, body mass: 78.3 ± 8.1 kg; % body fat: 14.3 ± 2.7%) volunteered to execute three randomly scheduled 10-min HIIT exercises at 110% vVO2max , Δ15% ASR, or Δ25% ASR. Analysis of variance for repeated measures and the least significant difference post-hoc test were used to compare the physiological responses and the mean of individual residuals between the training sessions. The coefficients of variation (CV) of time spent ≥90% of maximal oxygen uptake (VO2max ) and maximal heart rate (HRmax ), peak VO2 , mean VO2 , peak HR, mean HR, blood lactate [La], and rating of perceived exertion (RPE) were 48.7%, 35.9%, 9.3%, 7%, 3.5%, 4.8%, 32%, and 16.9% during 110% vVO2max , 47.2%, 31%, 7.5%, 6.7%, 3.9%, 4.6%, 24.2%, and 14.6% during Δ15% ASR, and 48.1%, 31.5%, 7.6%, 8.4%, 3.6%, 4.1%, 20.2%, and 3.4% during Δ25% ASR session, respectively. Only the residuals in RPE were significantly (p < 0.001) higher in 110% vVO2max and Δ15% ASR in comparison to Δ25% ASR. Time spent ≥90% HRmax /VO2max was maximized during Δ15% ASR session, albeit this was not significantly different from other sessions. The ASR-based method leads to reduced CVs of physiological and perceptual responses during 10-min HIIT; however, only reductions in [La] and RPE may be considered practically meaningful. Practitioners can use vVO2max for prescription of 10-min HIIT session comprised of 15-s work and passive recovery intervals.

Different MRI structural processing methods do not impact functional connectivity computation

Resting-state functional magnetic resonance imaging (rs-fMRI) has become an increasingly popular technique. This technique can assess several features of brain connectivity, such as inter-regional temporal correlation (functional connectivity), from which graph measures of network organization can be derived. However, these measures are prone to a certain degree of variability depending on the analytical steps during preprocessing. Many studies have investigated the effect of different preprocessing steps on functional connectivity measures; however, no study investigated whether different structural reconstructions lead to different functional connectivity metrics. Here, we evaluated the impact of different structural segmentation strategies on functional connectivity outcomes. To this aim, we compared different metrics computed after two different registration strategies. The first strategy used structural information from the 3D T1-weighted image (unimodal), while the second strategy implemented a multimodal approach, where an additional registration step used the information from the T2-weighted image. The impact of these different approaches was evaluated on a sample of 58 healthy adults. As expected, different approaches led to significant differences in structural measures (i.e., cortical thickness, volume, and gyrification index), with the maximum impact on the insula cortex. However, these differences were only slightly translated to functional metrics. We reported no differences in graph measures and seed-based functional connectivity maps, but slight differences in the insula when we compared the mean functional strength for each parcel. Overall, these results suggested that functional metrics are only slightly different when using a unimodal compared to a multimodal approach, while the structural output can be significantly affected.

Internal Morphological Variability of Mandibular Premolars in North Indian Population

Aims: The current study aims to investigate the root canal morphology of root canals of mandibular premolar teeth via cone-beam computed tomography (CBCT) among a sample of the north Indian population.&#x0D; Study Design: Retrospective observational study.&#x0D; Place and Duration of Study: Department of conservative dentistry and endodontics.&#x0D; Methodology: A total of 240 CBCT images were examined in the study. The Mandibular premolars were identified, and canal configurations were classified according to vertucci classification. Root canal configurations were investigated using a chi-square test.&#x0D; Results: Of the total 240 Mandibular premolars, vertucci type I was found in 86.66% in Mandibular first premolars followed by type v (8.33%) and type iv (5%). Vertucci type I was found in 96.6% in Mandibular second premolars followed by type v (1.66%), type iii (0.8%) and type viii (0.8%).&#x0D; Conclusion: The root morphology of Mandibular premolars in the north Indian population demonstrated a high degree of variability. However, the clinician should be aware about the possible anatomic variations of these teeth and their relationship with the adjacent anatomic structures while planning and performing endodontic, restorative, periodontal, and surgical procedures.

Linear type traits that characterize body development as the predictors of lifetime of Ukrainian Black-and-White dairy and Holstein cows

The researches were conducted in the aspect of studying the problem of dairy cows lifetime depending on the linear traits assessment of the conformation type. By the linear classification method were estimated firstborn cows of the Ukrainian Black-and-White dairy (UBWD) and Holstein (H) breeds. Descriptive traits of the conformation that characterize the overall body structure were studied: chest width, body depth, angularity, body condition, rear width and position. According to the research results, the relative variability of the descriptive type traits assessment with cow's lifetime was determined. The relative variability of chest width and cow's lifetime was curvilinear. Cows for chest width assessment of 4–7 score had a higher lifespan with a variability of 2704–2844 (UBWD) and 2688–2789 (H) days. The highest lifetime was in animals with an assessment for body depth development of 6-9 score with an unreliable predominance of Ukrainian Black-and-White dairy breed cows, with the highest grades of both breeds 2824 (UBWD) and 2802 (H) days with an assessment of 9 score. Animals with an optimal angularity estimation of 5 score differed, lived the longest – 2842 (UBWD) and 2828 (H) days, while with increasing and decreasing score for this trait, the number of lifetime days of cows declined. According to the rump width assessment, lifespan was highest in cows with a 9 score – 2766 days (UBWD) and 2832 days (H). Cows of UBWD with the highest assessment for this body part development of 9 score were used on 592 (P &lt;0.001), and Holstein on 708 (P &lt;0.001) days longer compared to animals with 1 score. The maximum lifetime of animals with an average assessment for body condition of 5 score was 2842 (UBWD) and 2774 (H) days. Cows with body condition score below average lived and were used in the herd much longer than with a higher one. The degree of relationship variability between the assessment of these traits and the lifetime of animals depended on the specific body part. Key words: Ukrainian Black-and-White dairy breed, Holstein, linear type traits, lifetime.

Microbiological profiling and knowledge of food preservation technology to support guidance on a neutropenic diet for immunocompromised patients.

The current society consists of an increasing number of people vulnerable to infections. For certain people with severe immunodeficiency, a neutropenic or low-microbial diet is being prescribed, which substitutes high-risk foods that are more likely to contain human (opportunistic) pathogens with lower-risk alternatives. These neutropenic dietary guidelines are typically set up from a clinical and nutritional perspective, rather than from a food processing and food preservation perspective. In this study, the current guidelines in use by the Ghent University Hospital were evaluated based on the current knowledge of food processing and preservation technologies and the scientific evidence on microbiological quality, safety, and hygiene of processed foods. Three criteria are identified to be important: (1) the microbial contamination level and composition; (2) the potential presence of established foodborne pathogens such as Salmonella spp. (to which a zero-tolerance policy is recommended); and (3) an increased vigilance for L. monocytogenes as an opportunistic foodborne pathogen with a high mortality rate in immunocompromised individuals (to which a zero-tolerance policy should apply). A combination of these three criteria was used as a framework for the evaluation of the suitability of foodstuffs to be included in a low-microbial diet. Differences in processing technologies, initial contamination of products, etc., however, lead to a high degree of variability in microbial contamination and make it difficult to unambiguously accept or reject a certain type of foodstuff without prior knowledge of the ingredients and the processing and preservation technologies applied during manufacturing and subsequent storage conditions. A restricted screening on a selection of (minimally processed) plant-based foodstuffs on the retail market in Flanders, Belgium supported decision-making on the inclusion of these food types in a low-microbial diet. Still, when determining the suitability of a foodstuff to be included in a low-microbial diet, not only the microbiological status but also nutritional and sensorial properties should be assessed, which requires multidisciplinary communication and collaboration.

Propensity of Patient-Derived iPSCs for Retinal Differentiation: Implications for Autologous Cell Replacement.

Prior to use, newly generated induced pluripotent stem cells (iPSC) should be thoroughly validated. While excellent validation and release testing assays designed to evaluate potency, genetic integrity, and sterility exist, they do not have the ability to predict cell type-specific differentiation capacity. Selection of iPSC lines that have limited capacity to produce high-quality transplantable cells, places significant strain on valuable clinical manufacturing resources. The purpose of this study was to determine the degree and root cause of variability in retinal differentiation capacity between cGMP-derived patient iPSC lines. In turn, our goal was to develop a release testing assay that could be used to augment the widely used ScoreCard panel. IPSCs were generated from 15 patients (14-76 years old), differentiated into retinal organoids, and scored based on their retinal differentiation capacity. Despite significant differences in retinal differentiation propensity, RNA-sequencing revealed remarkable similarity between patient-derived iPSC lines prior to differentiation. At 7 days of differentiation, significant differences in gene expression could be detected. Ingenuity pathway analysis revealed perturbations in pathways associated with pluripotency and early cell fate commitment. For example, good and poor producers had noticeably different expressions of OCT4 and SOX2 effector genes. QPCR assays targeting genes identified via RNA sequencing were developed and validated in a masked fashion using iPSCs from 8 independent patients. A subset of 14 genes, which include the retinal cell fate markers RAX, LHX2, VSX2, and SIX6 (all elevated in the good producers), were found to be predictive of retinal differentiation propensity.

Documenting heritage language experience using questionnaires.

There exists a great degree of variability in the documentation of multilingual experience across different instruments. The present paper contributes to the "methods turn" and individual differences focus in (heritage) bilingualism by proposing a comprehensive online questionnaire building on existing questionnaires and the experience of using them to document heritage bilingualism: the Heritage Language Experience (HeLEx) online questionnaire. HeLEx is validated against and contrasted to an extended version of the Language and Social Background Questionnaire designed for heritage speakers (HSs), LSBQ-H. We compare data elicited with both questionnaires in turn from a group of Turkish HSs (n = 174, mean age=32). Our validation focuses on traditional language background variables, including language exposure and use, language proficiency, language dominance, as well as a more novel measure of language entropy. The analyses are based on a subset of key questions from each questionnaire that capture language experience for up to five languages, four modalities, and five social contexts. In a subsequent set of analyses, we explore the impact of different types of response scales, response mechanisms, and manners of variable derivation on the informativity of the data they can provide, in terms of the scope, granularity and distributional properties of the derived measures. Our results show that both HeLEx and LSBQ-H are successful at detecting the important distributional patterns in the data and reveal a number of advantages of HeLEx. In the discussion, we consider the impact of methodological choices regarding question phrasing, visual format, response options, and response mechanisms. We emphasize that these choices are not trivial and can affect the derived measures and subsequent analyses on the impact of individual differences on language acquisition and processing.

Setting a reference for wetland carbon: the importance of accounting for hydrology, topography, and natural variability

Wetland soils are a key global sink for organic carbon (C) and a focal point for C management and accounting efforts. The ongoing push for wetland restoration presents an opportunity for climate mitigation, but C storage expectations are poorly defined due to a lack of reference information and an incomplete understanding of what drives natural variability among wetlands. We sought to address these shortcomings by (1) quantifying the range of variability in wetland soil organic C (SOC) stocks on a depressional landscape (Delmarva Peninsula, USA) and (2) investigating the role of hydrology and relative topography in explaining variability among wetlands. We found a high degree of variability within individual wetlands and among wetlands with similar vegetation and hydrogeomorphic characteristics. This suggests that uncertainty should be presented explicitly when inferring ecosystem processes from wetland types or land cover classes. Differences in hydrologic regimes, particularly the rate of water level recession, explained some of the variability among wetlands, but relationships between SOC stocks and some hydrologic metrics were eclipsed by factors associated with separate study sites. Relative topography accounted for a similar portion of SOC stock variability as hydrology, indicating that it could be an effective substitute in large-scale analyses. As wetlands worldwide are restored and focus increases on quantifying C benefits, the importance of appropriately defining and assessing reference systems is paramount. Our results highlight the current uncertainty in this process, but suggest that incorporating landscape heterogeneity and drivers of natural variability into reference information may improve how wetland restoration is implemented and evaluated.

Diagnosis of patients with facial neuropathy by practicing neurologists: online survey

Introduction. Diagnosis of patients with facial neuropathy (FN) is challenging because different sources of medical information off er a wide variety of approaches. Aim. Analysis of the features of diagnosing patients with FN by practicing neurologists. Material and methods. Anonymous online survey of neurologists adhering to the principles of evidence-based medicine (n = 172, work experience — 6 [3; 11] years), including 10 questions. Results. In 56.4% of cases, doctors diagnose patients with FN in accordance with “foreign” guidelines, however, older specialists still prefer Russian sources, and doctors with little work experience prefer the experience of colleagues (p = 0.018). Scales of assessment of facial muscles function are used by 28.5% of specialists, the description method is used by 95.9%. The content of the clinical protocol varies considerably. A highly significant correlation was observed: the lower the muscle is located on the face, the less often its function is assessed (r = –0.938, p &lt; 0.000). Less than 1/3 of doctors use tests to assess the function of the facial muscles of the lower third of the face. Doctors significantly more often focus on the manifestations of the disease (decrease in the strength and tone of facial muscles, lagophthalmos, hyperacusis) than on the complications of FN (increased muscle tone on the healthy or affected side, synkinesis, post-paralytic hemispasm), p &lt; 0.000. Magnetic resonance imaging is prescribed by more than 70% of specialists, computed tomography — by 25%, stimulation electroneuromyography — by 38,4% (in 1/4 of cases only on the affected side of the face). More than 95% of neurologists refer patients for consultations to doctors of other specialties, mainly to an otorhinolaryngologist (58.7%) and an ophthalmologist (56.9%), and only 23.2% to surgical specialists. About 2/3 of doctors refer patients for rehabilitation, however, there is no clinical protocol for the rehabilitation of this pathology. Conclusion. The study showed a greater adherence of the interviewed Russian specialists to evidence-based medicine, as well as a high degree of inter-expert variability of opinions, which dictates the necessity of the development of Russian guidelines.

Hidden diversity: DNA metabarcoding reveals hyper-diverse benthic invertebrate communities

BackgroundFreshwater ecosystems, such as streams, are facing increasing pressures from agricultural land use and recent literature stresses the importance of robust biomonitoring to detect trends in insect decline globally. Aquatic insects and other macroinvertebrates are often used as indicators of ecological condition in freshwater biomonitoring programs; however, these diverse groups can present challenges to morphological identification and coarse-level taxonomic resolution can mask patterns in community composition. Here, we incorporate molecular identification (DNA metabarcoding) into a stream biomonitoring sampling design to explore the diversity and variability of aquatic macroinvertebrate communities at small spatial scales. While individual stream reaches can be very heterogenous, most community ecology studies focus on larger, landscape-level patterns of community composition. A high degree of community variability at the local scale has important implications for both biomonitoring and ecological research, and the incorporation of DNA metabarcoding into local biodiversity assessments will inform future sampling protocols.ResultsWe sampled twenty streams in southern Ontario, Canada, for aquatic macroinvertebrates across multiple time points and assessed local community variability by comparing field replicates taken ten meters apart within the same stream. Using bulk-tissue DNA metabarcoding, we revealed that aquatic macroinvertebrate communities are highly diverse at small spatial scales with unprecedented levels of local taxonomic turnover. We detected over 1600 Operational Taxonomic Units (OTUs) from 149 families, and a single insect family, the Chironomidae, contained over one third of the total number of OTUs detected in our study. Benthic communities were largely comprised of rare taxa detected only once per stream despite multiple biological replicates (24–94% rare taxa per site). In addition to numerous rare taxa, our species pool estimates indicated that there was a large proportion of taxa that remained undetected by our sampling regime (14–94% per site). Our sites were located across a gradient of agricultural activity, and while we predicted that increased land use would homogenize benthic communities, this was not supported as within-stream dissimilarity was unrelated to land use. Within-stream dissimilarity estimates were consistently high for all levels of taxonomic resolution (invertebrate families, invertebrate OTUs, chironomid OTUs), indicating stream communities are very dissimilar at small spatial scales.

Environmental and climate variability drive population size of annual penaeid shrimp in a large lagoonal estuary.

Species with short life spans frequently show a close relationship between population abundance and environmental variation making these organisms potential indicator species of climatic variability. White (Penaeus setiferus), brown (P. aztecus), and pink (P. duorarum) penaeid shrimp typically have an annual life history and are of enormous ecological, cultural, and economic value to the southeastern United States and Gulf of Mexico. Within North Carolina, all three species rely on the Pamlico Sound, a large estuarine system that straddles Cape Hatteras, one of the most significant climate and biogeographic breaks in the world, as a nursery area. These characteristics make penaeid species within the Pamlico Sound a critical species-habitat complex for assessing climate impacts on fisheries. However, a comprehensive analysis of the influence of the environmental conditions that influence penaeid shrimp populations has been lacking in North Carolina. In this study, we used more than 30 years of data from two fishery-independent trawl surveys in the Pamlico Sound to examine the spatial distribution and abundance of adult brown, white, and pink shrimp and the environmental drivers associated with adult shrimp abundance and juvenile brown shrimp recruitment using numerical models. Brown shrimp recruitment models demonstrate that years with higher temperature, salinity, offshore windstress, and North Atlantic Oscillation phase predict increased abundance of juveniles. Additionally, models predicting adult brown, white, and pink shrimp abundance illustrate the importance of winter temperatures, windstress, salinity, the North Atlantic Oscillation index, and the abundance of spawning adult populations from the previous year on shrimp abundance. Our findings show a high degree of variability in shrimp abundance is explained by climate and environmental variation and indicate the importance of understanding these relationships in order to predict the impact of climate variability within ecosystems and develop climate-based adaptive management strategies for marine populations.

Familial traits of bipolar disorder: A systematic review and meta-analysis.

Genetic studies of bipolar disorder (BD) have shown varied results, which is in part because of the heterogeneity of the disorder. Identifying clinical phenotypes of BD could reduce variability and benefit research. Since BD has a robust genetic component, studies can investigate clinical traits that cluster in families to identify phenotypes with a probable genetic basis. We conducted a systematic review of the current literature on familial clinical traits of BD. Text screening and data extraction were performed independently by two reviewers, and random effects meta-analysis was used. Of 1117 unique records, 16 studies met inclusion criteria. These studies indicated 14 potentially familial traits of BD: age of onset (OR: 4.50; 95% CI: [3.25, 6.22]), bipolar type (OR: 2.05 [1.50, 2.79]), lithium response (OR: 3.71 [1.28, 10.82]), polarity at onset (OR: 1.17 [1.03, 1.34]), psychotic features (OR: 2.20 [1.51, 3.20]), mood-incongruent psychosis (OR: 2.52 [1.66, 3.83]), puerperal psychosis (OR: 6.54 [2.55, 16.77]), rapid cycling (OR: 4.95 [0.96, 25.40]), suicide attempt (OR: 1.04 [0.65, 1.67]), alcoholism (OR: 1.53 [1.09, 2.16]), obsessive-compulsive disorder (OR: 3.10 [1.31; 7.09]), panic disorder (OR: 2.69 [1.12; 6.48]), social anxiety disorder (OR: 1.00 [0.39, 2.55]), and specific phobia (OR: 1.94 [0.95; 3.96]). For most traits, tests of heterogeneity were significant and publication bias was likely. The results of our review and meta-analysis highlight the lack of studies investigating familial clinical traits of BD, despite the need to address heterogeneity. The large degree of variability between studies must be reduced for future research.