Edge states in rationally terminated honeycomb structures.

Consider the tight binding model of graphene, sharply terminated along an edge l parallel to a direction of translational symmetry of the underlying period lattice. We classify such edges l into those of "zigzag type" and those of "armchair type," generalizing the classical zigzag and armchair edges. We prove that zero-energy/flat-band edge states arise for edges of zigzag type, but never for those of armchair type. We exhibit explicit formulae for flat-band edge states when they exist. We produce strong evidence for the existence of dispersive (nonflat) edge state curves of nonzero energy for most l.

Women with chronic constipation have more bothersome urogenital symptoms.

BACKGROUND: The aim of our study was to characterize urogenital symptoms in women with and without constipation, and by severity of constipation. METHODS: This was a retrospective cohort study conducted at a pelvic floor disorder center in a tertiary healthcare facility from May 2007 through August 2019 and completed an intake questionnaire were included. We collected demographic, physical exam data and quality of life outcomes. The Urinary Distress Inventory (UDI-6) was used to assess urogenital symptoms. Women with constipation completed the Constipation Severity Instrument (CSI). We excluded women with a history of a bowel resection, inflammatory bowel disease, or pelvic organ prolapse symptoms. The cohort was then divided into two groups, constipated and non-constipated, and the prevalence and severity of urogenital-associated symptoms were compared. A secondary analysis was made among constipated subjects stratified by constipation severity based on CSI scores. RESULTS: During the study period, 875 women (59.5%) had chronic constipation. Women with chronic constipation were more likely to experience urogenital symptoms, such as dyspareunia, urinary hesitancy, and a sensation of incomplete bladder emptying (all p < 0.05). Moreover, on univariate analysis, women with high CSI scores (75 percentile or higher) were found to have higher UDI-6 scores, increased bladder splinting, pad use, urinary frequency and dyspareunia while on multivariate analysis higher UDI score, increased bladder splinting, urinary frequency and dyspareunia were significantly associated (p < 0.05). CONCLUSION: We found that the presence and severity of chronic constipation worsened the degree of bother from urogenital symptoms. Given that chronic constipation can modulate urogenital symptoms, our study suggests that pelvic floor specialists should assess the presence and severity of urogenital and bowel symptoms to provide comprehensive care.

The role of citizen science in addressing grand challenges in food and agriculture research.

The power of citizen science to contribute to both science and society is gaining increased recognition, particularly in physics and biology. Although there is a long history of public engagement in agriculture and food science, the term 'citizen science' has rarely been applied to these efforts. Similarly, in the emerging field of citizen science, most new citizen science projects do not focus on food or agriculture. Here, we convened thought leaders from a broad range of fields related to citizen science, agriculture, and food science to highlight key opportunities for bridging these overlapping yet disconnected communities/fields and identify ways to leverage their respective strengths. Specifically, we show that (i) citizen science projects are addressing many grand challenges facing our food systems, as outlined by the United States National Institute of Food and Agriculture, as well as broader Sustainable Development Goals set by the United Nations Development Programme, (ii) there exist emerging opportunities and unique challenges for citizen science in agriculture/food research, and (iii) the greatest opportunities for the development of citizen science projects in agriculture and food science will be gained by using the existing infrastructure and tools of Extension programmes and through the engagement of urban communities. Further, we argue there is no better time to foster greater collaboration between these fields given the trend of shrinking Extension programmes, the increasing need to apply innovative solutions to address rising demands on agricultural systems, and the exponential growth of the field of citizen science.

Optimization of the thrombin generation test components to measure potency of factor VIII concentrates.

INTRODUCTION: The thrombin generation test (TGT) is used both as a global haemostasis assay, and to compare activities of coagulation factor concentrates that have been spiked into patient plasma. However, TGT has not been systematically optimized to evaluate factor VIII (FVIII) product potency. AIMS: To improve the sensitivity of TGT to FVIII and allow a comparative analysis of the thrombin generating capacities of FVIII concentrates against reference preparations with known FVIII activity. METHODS: Concentrations of TGT components (analytical variables) were assessed to maximize the linearity and range of responses to the concentration of FVIII. RESULTS: We optimized the range and sensitivity of the TGT assay with respect to FVIII through the addition of FXIa to the assay. Other parameters that were adjusted, i.e. tissue factor (TF), procoagulant lipids and plasma concentrations, did not improve the ability of the assay to measure both high and very low levels of FVIII. In the optimized TF/FXIa-activated TGT assay, all thrombin generation curve parameters were suitable for FVIII quantification, but thrombin peak height and maximal velocity demonstrated better linearity in the desired FVIII range. We found that the optimized TF/FXIa-activated TGT has a wider range of sensitivity to FVIII than a commercially available TGT. Additionally, we demonstrated that the TF/FXIa-activated assay performs adequately by comparing potency measurements of five commercially available FVIII products using TGT and traditional chromogenic and one-stage clotting assays. CONCLUSIONS: The optimized TGT assay can be used to quantify and compare the thrombin generating capacities of FVIII concentrates.

Impaired diffusion tensor imaging findings in the corpus callosum and cingulum may underlie impaired learning and memory abilities in systemic lupus erythematosus.

BACKGROUND: Memory impairment is prevalent in systemic lupus erythematosus (SLE); however, its pathogenesis is unknown. In a previous functional magnetic resonance imaging (fMRI) study we demonstrated altered brain activity dynamics and less brain deactivation in patients with SLE as compared with healthy controls, when performing a learning and memory task. Our findings localized this impairment to the default mode network (DMN), and particularly to its anterior medial prefrontal cortex node. In addition, altered networking of the hippocampal subsystem of the DMN was seen in patients with SLE when performing this task, as well as atrophy of the left hippocampus. The present study aimed to search for a structural substrate for the altered recruitment pattern observed in fMRI studies using diffusion tensor imaging (DTI). PATIENTS AND METHODS: Using DTI, we characterized brain diffusivity in 10 patients with SLE and nine healthy controls. Two tracts associated with the DMN were reconstructed: the corpus callosum (CC) and the cingulum bundle. The CC was segmented according to the Witelson segmentation scheme and the cingulum was segmented into superior and descending bundles. RESULTS: A significant increase in mean diffusivity (MD) was seen in patients with SLE without neuropsychiatric SLE (NPSLE) as compared with healthy controls in all five segments of the CC (segment 1: p = 0.043; segment 2: p = 0.005; segment 3: p = 0.003; segment 4: p = 0.012; segment 5: p = 0.023) as well as in the descending portion of the left cingulum bundle (p = 0.026). CONCLUSIONS: Increased MD values in the CC and the left cingulum may indicate impaired organization/reduced integrity of these tracts, which may underlie the abnormal pattern of brain activity recruitment of the DMN observed during a verbal learning and memory task. Taking into account the central role of the left hippocampus in verbal memory, the abnormal integrity of the left cingulum may contribute to the reduced performance of patients with SLE on verbal memory tasks.

The effect of preexisting hypertension on early neurologic results of patients with an acute spinal cord injury.

STUDY DESIGN: Retrospective case-control. OBJECTIVES: To characterize changes in American Spinal Injury Association Motor Score (AMS) in patients treated with relative hypertension (HTN) (mean arterial pressure (MAP) > 85 mm Hg for 5 days) with and without preexisting HTN. SETTING: A regional spinal cord injury (SCI) center in Pennsylvania, United States. METHODS: All patients with an acute SCI who were treated with induced HTN (MAP goal above 85) in the intensive care unit (ICU) for at least 5 days were identified. Patients were stratified based on the presence of preexisting HTN, and the change in the AMS between admission and day 5 was determined. Predictors of outcome were identified using correlation analysis and multiple linear regression. RESULTS: Ninety-two patients met inclusion criteria of which 22 had a previous history of HTN. HTN was a predictor of poor early outcome. Patients with HTN had an average decline in their AMS of 7.6, compared with an average decrease of only 0.6 in the AMS of patients without HTN (P=0.04). HTN had no effect (P>0.05) on other in-hospital variables including length of stay, length of stay in the ICU, complications or mortality. Additionally, multiple linear regression analysis demonstrated that diabetes, coronary artery disease and pulmonary disease had no effect on the change in AMS. CONCLUSION: Chronic HTN is an independent risk factor for poor early neurologic recovery in patients treated with relative HTN for an acute SCI. This is independent of age and other comorbidities.

Controlled clinical comparison of BacT/alert FA plus and FN plus blood culture media with BacT/alert FA and FN blood culture media.

New blood culture media containing antibiotic-binding polymeric beads have been developed for the BacT/Alert (bioMérieux, Inc., Durham, NC) blood culture system. To assess the performance of these new media, we compared the new BacT/Alert aerobic medium (FA Plus) with resins to BacT/Alert FA medium with activated charcoal and the new BacT/Alert anaerobic medium (FN Plus) to BacT/Alert FN medium at 3 tertiary care medical centers. Study bottle pairs were inoculated with a target volume of 6 to 10 ml of blood from adults and incubated in the BacT/Alert 3D blood culture instrument. In the FA Plus versus FA comparison, there were 1,507 study pairs. Among 170 isolates causing true bloodstream infections (BSIs), significantly more Staphylococcus aureus (P<0.001) and total microorganisms (P<0.01) grew in the FA Plus bottle than in the FA bottle. Fewer coagulase-negative staphylococcal (CoNS) contaminants grew in the FA Plus bottle than in the FA bottle (10 versus 22; P=0.05). In addition, growth was detected earlier in the FA Plus bottle than in the FA bottle (P<0.001). In the FN Plus versus FN comparison, there were 2,386 study pairs. Among 201 isolates causing true BSIs, significantly more S. aureus (P<0.001), CoNS (P<0.005), and total microorganisms (P<0.001) grew in the FN Plus bottle than in the FN bottle. Also, significantly more CoNS contaminants grew in the FN Plus bottle than in the FN bottle (P<0.001). Overall, microorganisms were detected earlier in the FN Plus than in the FN bottle (P<0.001). Medical technologists at all 3 study sites preferred the new media for Gram stain interpretation. We conclude that the FA Plus and FN Plus media provide improved and earlier detection of microorganisms compared with the FA and FN media and are preferable for Gram stain interpretation as well.

Structural genomic variation and behavioral interactions underpin a balanced sexual mimicry polymorphism.

How phenotypic diversity originates and persists within populations are classic puzzles in evolutionary biology. While balanced polymorphisms segregate within many species, it remains rare for both the genetic basis and the selective forces to be known, leading to an incomplete understanding of many classes of traits under balancing selection. Here, we uncover the genetic architecture of a balanced sexual mimicry polymorphism and identify behavioral mechanisms that may be involved in its maintenance in the swordtail fish Xiphophorus birchmanni. We find that ∼40% of X. birchmanni males develop a "false gravid spot," a melanic pigmentation pattern that mimics the "pregnancy spot" associated with sexual maturity in female live-bearing fish. Using genome-wide association mapping, we detect a single intergenic region associated with variation in the false gravid spot phenotype, which is upstream of kitlga, a melanophore patterning gene. By performing long-read sequencing within and across populations, we identify complex structural rearrangements between alternate alleles at this locus. The false gravid spot haplotype drives increased allele-specific expression of kitlga, which provides a mechanistic explanation for the increased melanophore abundance that causes the spot. By studying social interactions in the laboratory and in nature, we find that males with the false gravid spot experience less aggression; however, they also receive increased attention from other males and are disdained by females. These behavioral interactions may contribute to the maintenance of this phenotypic polymorphism in natural populations. We speculate that structural variants affecting gene regulation may be an underappreciated driver of balanced polymorphisms across diverse species.

A deceptive case of cellulitis caused by a Gram-negative pathogen.

Yokenella regensburgei is a member of the family Enterobacteriaceae that has rarely been implicated in clinical disease. We report here a case of septicemia with a skin and soft tissue source caused by Y. regensburgei in an immunocompromised host.

Controlled multicenter evaluation of a bacteriophage-based method for rapid detection of Staphylococcus aureus in positive blood cultures.

Staphylococci are a frequent cause of bloodstream infections (BSIs). Appropriate antibiotic treatment for BSIs may be delayed because conventional laboratory testing methods take 48 to 72 h to identify and characterize isolates from positive blood cultures. We evaluated a novel assay based on bacteriophage amplification that identifies Staphylococcus aureus and differentiates between methicillin-susceptible and methicillin-resistant S. aureus (MSSA and MRSA, respectively) in samples taken directly from signal-positive Bactec blood culture bottles within 24 h of positive signal, with results available within 5 h. The performance of the MicroPhage KeyPath MRSA/MSSA blood culture test was compared to conventional identification and susceptibility testing methods. At four sites, we collectively tested a total of 1,165 specimens, of which 1,116 were included in our analysis. Compared to standard methods, the KeyPath MRSA/MSSA blood culture test demonstrated a sensitivity, specificity, positive predictive value, and negative predictive value of 91.8%, 98.3%, 96.3%, and 96.1%, respectively, for correctly identifying S. aureus. Of those correctly identified as S. aureus (n = 334), 99.1% were correctly categorized as either MSSA or MRSA. Analysis of a subset of the data revealed that the KeyPath MRSA/MSSA blood culture test delivered results a median of 30 h sooner than conventional methods (a median of 46.9 h versus a median of 16.9 h). Although the sensitivity of the test in detecting S. aureus-positive samples is not high, its accuracy in determining methicillin resistance and susceptibility among positives is very high. These characteristics may enable earlier implementation of appropriate antibiotic treatment for many S. aureus BSI patients.

Are rectoceles the cause or the result of obstructed defaecation syndrome? A prospective anorectal physiology study.

AIM: To determine the relationship between obstructed defaecation syndrome (ODS) and rectoceles. METHOD: From December 2007 to November 2011, all female patients with ODS were prospectively evaluated with full interview, clinical examination and anorectal physiology testing. The characteristics of patients with and without rectoceles were compared, and logistic regression was utilized to identify factors predictive of patients having a rectocele beyond the introitus. RESULTS: Of 239 patients with ODS, 90 (mean age: 52.3 ± 1.7 years) had a rectocele. Patients with rectoceles (R+) had a similar prevalence of incomplete emptying compared with patients with no rectocele (R-) (P ≥ 0.21), but only R+ patients reported splinting with defaecation (36.7% vs 0%; P < 0.0001). Anorectal manometry measurements, including mean resting pressure, maximum resting pressure and maximum squeeze pressure, were similar between groups (P ≥ 0.12). There were also no significant differences in rectal compliance (maximum tolerated volume) or rectal sensitivity (volume of first sensation) (P ≥ 0.65). R+ patients had greater difficulty expelling a 60 cm(3) balloon (70.1% R+ patients vs 57.5% R- patients; P = 0.05), but the prevalence of pelvic floor dyssynergia, as quantified by nonrelaxation on electromyography (EMG) testing, was similar to that of R- patients (P = 0.49). Logistic regression suggested that only difficulty with balloon expulsion was associated with higher odds of having a rectocele (OR = 3.00; P = 0.002), whereas mean resting pressure, EMG nonrelaxation and symptoms of incomplete emptying were not (P ≥ 0.12). CONCLUSION: Rectoceles are not associated with an increased severity of ODS-type symptoms, anorectal abnormalities or pelvic floor dyssynergia in patients with ODS. This suggests that rectoceles may be the result, rather than the cause, of ODS.

Mice lacking Smad3 show accelerated wound healing and an impaired local inflammatory response.

The generation of animals lacking SMAD proteins, which transduce signals from transforming growth factor-beta (TGF-beta), has made it possible to explore the contribution of the SMAD proteins to TGF-beta activity in vivo. Here we report that, in contrast to predictions made on the basis of the ability of exogenous TGF-beta to improve wound healing, Smad3-null (Smad3ex8/ex8) mice paradoxically show accelerated cutaneous wound healing compared with wild-type mice, characterized by an increased rate of re-epithelialization and significantly reduced local infiltration of monocytes. Smad3ex8/ex8 keratinocytes show altered patterns of growth and migration, and Smad3ex8/ex8 monocytes exhibit a selectively blunted chemotactic response to TGF-beta. These data are, to our knowledge, the first to implicate Smad3 in specific pathways of tissue repair and in the modulation of keratinocyte and monocyte function in vivo.

A double-blind, randomized, placebo-controlled trial of topical tacrolimus 0·1% vs. clobetasol propionate 0·05% in childhood vitiligo.

BACKGROUND: Both clobetasol propionate 0·05% (CP 0·05%) and tacrolimus 0·1% (T 0·1%) ointments have been shown to be efficacious and safe in treating vitiligo in the paediatric population. OBJECTIVES: To assess efficacy and safety of these two therapies compared with each other and with placebo. METHODS: In this prospective study, children aged 2-16 years with vitiligo, stratified into 'facial' (n = 55) and 'nonfacial' (n = 45) groups, were randomized into three arms: CP 0·05% ointment (n = 30), T 0·1% ointment (n = 31) and placebo (n = 29) for 6 months. Successful repigmentation, defined as > 50% improvement, was evaluated by comparing photographs taken at baseline and at 2, 4 and 6 months. RESULTS: In the facial group, 58% of the CP 0·05% group responded successfully compared with 58% of the T 0·1% group, and in the nonfacial group, 39% of the CP 0·05% group responded compared with 23% of the T 0·1% group (P > 0·05). There was a significant difference in response between the CP 0·05% group vs. placebo (P < 0·0001) and the T 0·1% group vs. placebo (P = 0·0004). Spontaneous repigmentation was evaluated as 2·4%. No significant clinical adverse events were noted in any group. CONCLUSIONS: Both CP 0·05% and T 0·1% ointments offer similar benefit in paediatric vitiligo, both facial and nonfacial. The facial lesions responded faster than the nonfacial ones.

Lipid class dynamics and storage depots in juvenile weakfish Cynoscion regalis and their application to condition assessment.

Lipid class dynamics, the pattern of change in the primary form and location of lipid stores and their relationship with standard length (L(S) ), were investigated in collections of young-of-the-year weakfish Cynoscion regalis for the purpose of determining the utility of this analysis as an indication of condition. The separation of total lipids into individual classes and the analysis of potential storage depots revealed the general patterns of lipid class dynamics and energy storage in C. regalis during their period of juvenile estuarine residency. Phospholipid and cholesterol exhibited moderate but variable (8·1-40·0 and 1·3-21·5 mg g(-1) , respectively) concentrations across the entire juvenile period and were the predominant lipid classes in juveniles <100 mm L(S) , while wax ester concentrations were low (c. 1 mg g(-1) ) and exhibited the least amount of variability among lipid classes. Triacylglycerols (TAG) and free fatty acids (FFA) exhibited similar dynamics, with relatively low concentrations (<15 mg g(-1) ) in individuals ≤100 mm L(S) . In larger juveniles both TAG and FFA concentrations generally increased rapidly, though there was considerable variability in both measures (0·0-199·7 and 0·0-49·7 mg g(-1) , respectively). Increasing levels of lipids, primarily in the form of TAG, with size indicated an accumulation of energy reserves with growth, thus providing an indication of individual condition for larger juveniles. Separate analysis of liver, viscera and the remaining carcass indicated that liver and viscera did not represent a significant depot of TAG reserves. Analysis of samples derived from whole juvenile C. regalis thus provided an accurate estimate of energy reserves.

MyoD-positive myoblasts are present in mature fetal organs lacking skeletal muscle.

The epiblast of the chick embryo gives rise to the ectoderm, mesoderm, and endoderm during gastrulation. Previous studies revealed that MyoD-positive cells were present throughout the epiblast, suggesting that skeletal muscle precursors would become incorporated into all three germ layers. The focus of the present study was to examine a variety of organs from the chicken fetus for the presence of myogenic cells. RT-PCR and in situ hybridizations demonstrated that MyoD-positive cells were present in the brain, lung, intestine, kidney, spleen, heart, and liver. When these organs were dissociated and placed in culture, a subpopulation of cells differentiated into skeletal muscle. The G8 antibody was used to label those cells that expressed MyoD in vivo and to follow their fate in vitro. Most, if not all, of the muscle that formed in culture arose from cells that expressed MyoD and G8 in vivo. Practically all of the G8-positive cells from the intestine differentiated after purification by FACS. This population of ectopically located cells appears to be distinct from multipotential stem cells and myofibroblasts. They closely resemble quiescent, stably programmed skeletal myoblasts with the capacity to differentiate when placed in a permissive environment.

DNA dendrimers localize MyoD mRNA in presomitic tissues of the chick embryo.

MyoD expression is thought to be induced in somites in response to factors released by surrounding tissues; however, reverse transcription-PCR and cell culture analyses indicate that myogenic cells are present in the embryo before somite formation. Fluorescently labeled DNA dendrimers were used to identify MyoD expressing cells in presomitic tissues in vivo. Subpopulations of MyoD positive cells were found in the segmental plate, epiblast, mesoderm, and hypoblast. Directly after laying, the epiblast of the two layered embryo contained approximately 20 MyoD positive cells. These results demonstrate that dendrimers are precise and sensitive reagents for localizing low levels of mRNA in tissue sections and whole embryos, and that cells with myogenic potential are present in the embryo before the initiation of gastrulation.

Cost-effective priorities for cancer prevention.

Faced with limited resources, the United States must set priorities for research to identify preventable causes of cancer. A quantitative approach to priority setting, based on principles of decision analysis and cost-effectiveness analysis, can offer guidance in this process. An illustrative application of such a model suggests that the National Institutes of Health-supported clinical trial of dietary beta-carotene offers a greater expected reduction in cancer mortality per research dollar than carcinogen bioassays of high-volume industrial chemicals such as p-dichlorobenzene. National research priorities should reflect the relative cost-effectiveness of such investments.