Nanopores map the acid-base properties of a single site in a single DNA molecule.

Nanopores are increasingly powerful tools for single molecule sensing, in particular, for sequencing DNA, RNA and peptides. This success has spurred efforts to sequence non-canonical nucleic acid bases and amino acids. While canonical DNA and RNA bases have pKas far from neutral, certain non-canonical bases, natural RNA modifications, and amino acids are known to have pKas near neutral pHs at which nanopore sequencing is typically performed. Previous reports have suggested that the nanopore signal may be sensitive to the protonation state of an individual moiety. We sequenced ion currents with the MspA nanopore using a single stranded DNA containing a single non-canonical DNA base (Z) at various pH conditions. The Z-base has a near-neutral pKa ∼ 7.8. We find that the measured ion current is remarkably sensitive to the protonation state of the Z-base. We demonstrate how nanopores can be used to localize and determine the pKa of individual moieties along a polymer. More broadly, these experiments provide a path to mapping different protonation sites along polymers and give insight in how to optimize sequencing of polymers that contain moieties with near-neutral pKas.

The Performance of ChatGPT-4 and Gemini Ultra 1.0 for Quality Assurance Review in Emergency Medical Services Chest Pain Calls.

OBJECTIVES: This study assesses the feasibility, inter-rater reliability, and accuracy of using OpenAI's ChatGPT-4 and Google's Gemini Ultra large language models (LLMs), for Emergency Medical Services (EMS) quality assurance. The implementation of these LLMs for EMS quality assurance has the potential to significantly reduce the workload on medical directors and quality assurance staff by automating aspects of the processing and review of patient care reports. This offers the potential for more efficient and accurate identification of areas requiring improvement, thereby potentially enhancing patient care outcomes. METHODS: Two expert human reviewers, ChatGPT GPT-4, and Gemini Ultra assessed and rated 150 consecutively sampled and anonymized prehospital records from 2 large urban EMS agencies for adherence to 2020 National Association of State EMS metrics for cardiac care. We evaluated the accuracy of scoring, inter-rater reliability, and review efficiency. The inter-rater reliability for the dichotomous outcome of each EMS metric was measured using the kappa statistic. RESULTS: Human reviewers showed high interrater reliability, with 91.2% agreement and a kappa coefficient 0.782 (0.654-0.910). ChatGPT-4 achieved substantial agreement with human reviewers in EKG documentation and aspirin administration (76.2% agreement, kappa coefficient 0.401 (0.334-0.468), but performance varied across other metrics. Gemini Ultra's evaluation was discontinued due to poor performance. No significant differences were observed in median review times: 01:28 min (IQR 1:12 - 1:51 min) per human chart review, 01:24 min (IQR 01:09 - 01:53 min) per ChatGPT-4 chart review (p = 0.46), and 01:50 min (IQR 01:10-03:34 min) per Gemini Ultra review (p = 0.06). CONCLUSIONS: Large language models demonstrate potential in supporting quality assurance by effectively and objectively extracting data elements. However, their accuracy in interpreting non-standardized and time-sensitive details remains inferior to human evaluators. Our findings suggest that current LLMs may best offer supplemental support to the human review processes, but their current value remains limited. Enhancements in LLM training and integration are recommended for improved and more reliable performance in the quality assurance processes.

Acute effects of exercise-induced muscle damage on sprint and change of direction performance: A systematic review and meta-analysis.

The aim of this study is to determine the acute effects of resistance and plyometric training on sprint and change of direction (COD) performance in healthy adults and adolescents. A systematic literature search was conducted via Medline, Cinahl, Scopus and SportDiscus databases for studies that investigated: 1) healthy male, female adults, or adolescents; and 2) measured sprint or change of direction performance following resistance and plyometric exercises. Studies were excluded if: 1) resistance or plyometric exercises was not used to induce muscle damage; 2) conducted in animals, infants, elderly; 3) sprint performance and/or agility performance was not measured 24 h post muscle damaging protocol. Study appraisal was completed using the Kmet Quality Scoring for Quantitative Study tool. Forest plots were generated to quantitatively analyse data and report study statistics for statistical significance and heterogeneity. The included studies (n = 20) revealed sprint and COD performance was significantly impaired up to 72 hr following resistance and plyometric exercises; both protocols significantly increased creatine kinase (CK), delayed-onset muscle soreness (DOMS) and decreased countermovement jump (CMJ) up to 72 hr. The systematic review of 20 studies indicated that resistance and plyometric training significantly impaired sprint and COD performance up to 72 hours post-exercise. Both training protocols elevated exercise-induced muscle damage (EIMD) markers (CK, DOMS) and decreased CMJ performance within the same timeframe.

Assessing Readability of an 8-Letter Expanded Deoxyribonucleic Acid Alphabet with Nanopores.

Chemists have now synthesized new kinds of DNA that add nucleotides to the four standard nucleotides (guanine, adenine, cytosine, and thymine) found in standard Terran DNA. Such "artificially expanded genetic information systems" are today used in molecular diagnostics; to support directed evolution to create medically useful receptors, ligands, and catalysts; and to explore issues related to the early evolution of life. Further applications are limited by the inability to directly sequence DNA containing nonstandard nucleotides. Nanopore sequencing is well-suited for this purpose, as it does not require enzymatic synthesis, amplification, or nucleotide modification. Here, we take the first steps to realize nanopore sequencing of an 8-letter "hachimoji" expanded DNA alphabet by assessing its nanopore signal range using the MspA (Mycobacterium smegmatis porin A) nanopore. We find that hachimoji DNA exhibits a broader signal range in nanopore sequencing than standard DNA alone and that hachimoji single-base substitutions are distinguishable with high confidence. Because nanopore sequencing relies on a molecular motor to control the motion of DNA, we then assessed the compatibility of the Hel308 motor enzyme with nonstandard nucleotides by tracking the translocation of single Hel308 molecules along hachimoji DNA, monitoring the enzyme kinetics and premature enzyme dissociation from the DNA. We find that Hel308 is compatible with hachimoji DNA but dissociates more frequently when walking over C-glycoside nucleosides, compared to N-glycosides. C-glycocide nucleosides passing a particular site within Hel308 induce a higher likelihood of dissociation. This highlights the need to optimize nanopore sequencing motors to handle different glycosidic bonds. It may also inform designs of future alternative DNA systems that can be sequenced with existing motors and pores.

The addition of androgen deprivation therapy and pelvic lymph node treatment to prostate bed salvage radiotherapy (NRG Oncology/RTOG 0534 SPPORT): an international, multicentre, randomised phase 3 trial.

BACKGROUND: In men with a detectable prostate-specific antigen (PSA) level after prostatectomy for prostate cancer, salvage prostate bed radiotherapy (PBRT) results in about 70% of patients being free of progression at 5 years. A three-group randomised trial was designed to determine whether incremental gains in patient outcomes can be achieved by adding either 4-6 months of short-term androgen deprivation therapy (ADT) to PBRT, or both short-term ADT and pelvic lymph node radiotherapy (PLNRT) to PBRT. METHODS: The international, multicentre, randomised, controlled SPPORT trial was done at 283 radiation oncology cancer treatment centres in the USA, Canada, and Israel. Eligible patients (aged ≥18 years) were those who after prostatectomy for adenocarcinoma of the prostate had a persistently detectable or an initially undetectable and rising PSA of between 0·1 and 2·0 ng/mL. Patients with and without lymphadenectomy (N0/Nx) were eligible if there was no clinical or pathological evidence of lymph node involvement. Other eligibility criteria included pT2 or pT3 disease, prostatectomy Gleason score of 9 or less, and a Zubrod performance status of 0-1. Eligible patients were randomly assigned to receive PBRT alone at a dose of 64·8-70·2 Gy at 1·8 Gy per fraction daily (group 1), PBRT plus short-term ADT (group 2), or PLNRT (45 Gy at 1·8 Gy per fraction, and then a volume reduction made to the planning target volume for the remaining 19·8-25 ·2 Gy) plus PBRT plus short-term ADT (group 3). The primary endpoint was freedom from progression, in which progression was defined as biochemical failure according to the Phoenix definition (PSA ≥2 ng/mL over the nadir PSA), clinical failure (local, regional, or distant), or death from any cause. A planned interim analysis of 1191 patents with minimum potential follow-up time of 5 years applied a Haybittle-Peto boundary of p<0·001 (one sided) for comparison of 5-year freedom from progression rates between the treatment groups. This trial is registered with ClinicalTrials.gov, NCT00567580. The primary objectives of the trial have been completed, although long-term follow-up is continuing. FINDINGS: Between March 31, 2008, and March 30, 2015, 1792 eligible patients were enrolled and randomly assigned to the three treatment groups (592 to group 1 [PBRT alone], 602 to group 2 [PBRT plus short-term ADT], and 598 to group 3 [PLNRT plus PBRT plus short-term ADT]). 76 patients subsequently found to be ineligible were excluded from the analyses; thus, the evaluable patient population comprised 1716 patients. At the interim analysis (n=1191 patients; data cutoff May 23, 2018), the Haybittle-Peto boundary for 5-year freedom from progression was exceeded when group 1 was compared with group 3 (difference 17·9%, SE 2·9%; p<0·0001). The difference between groups 2 and 3 did not exceed the boundary (p=0·0063). With additional follow-up beyond the interim analysis (the final planned analysis; data cutoff May 26, 2021), at a median follow-up among survivors of 8·2 years (IQR 6·6-9·4), the 5-year freedom from progression rates in all 1716 eligible patients were 70·9% (95% CI 67·0-74·9) in group 1, 81·3% (78·0-84·6) in group 2, and 87·4% (84·7-90·2) in group 3. Per protocol criteria, freedom from progression in group 3 was superior to groups 1 and 2. Acute (≤3 months after radiotherapy) grade 2 or worse adverse events were significantly more common in group 3 (246 [44%] of 563 patients) than in group 2 (201 [36%] of 563; p=0·0034), which, in turn, were more common than in group 1 (98 [18%] of 547; p<0·0001). Similar findings were observed for grade 3 or worse adverse events. However, late toxicity (>3 months after radiotherapy) did not differ significantly between the groups, apart from more late grade 2 or worse blood or bone marrow events in group 3 versus group 2 (one-sided p=0·0060) attributable to the addition of PLNRT in this group. INTERPRETATION: The results of this randomised trial establish the benefit of adding short-term ADT to PBRT to prevent progression in prostate cancer. To our knowledge, these are the first such findings to show that extending salvage radiotherapy to treat the pelvic lymph nodes when combined with short-term ADT results in meaningful reductions in progression after prostatectomy in patients with prostate cancer. FUNDING: National Cancer Institute.

Thermotolerant coral-algal mutualisms maintain high rates of nutrient transfer while exposed to heat stress.

Symbiotic mutualisms are essential to ecosystems and numerous species across the tree of life. For reef-building corals, the benefits of their association with endosymbiotic dinoflagellates differ within and across taxa, and nutrient exchange between these partners is influenced by environmental conditions. Furthermore, it is widely assumed that corals associated with symbionts in the genus Durusdinium tolerate high thermal stress at the expense of lower nutrient exchange to support coral growth. We traced both inorganic carbon (H13CO3-) and nitrate (15NO3-) uptake by divergent symbiont species and quantified nutrient transfer to the host coral under normal temperatures as well as in colonies exposed to high thermal stress. Colonies representative of diverse coral taxa associated with Durusdinium trenchii or Cladocopium spp. exhibited similar nutrient exchange under ambient conditions. By contrast, heat-exposed colonies with D. trenchii experienced less physiological stress than conspecifics with Cladocopium spp. while high carbon assimilation and nutrient transfer to the host was maintained. This discovery differs from the prevailing notion that these mutualisms inevitably suffer trade-offs in physiological performance. These findings emphasize that many host-symbiont combinations adapted to high-temperature equatorial environments are high-functioning mutualisms; and why their increased prevalence is likely to be important to the future productivity and stability of coral reef ecosystems.

Hepatitis C virus prevalence among men who have sex with men: a cross-sectional study in 12 Brazilian cities.

BACKGROUND: Despite the preventive policies adopted, reduction in sexually transmitted infections (STIs) among men who have sex with men (MSM) has been limited. The risk of hepatitis C virus (HCV) infection has increased among the most vulnerable population groups, including MSM. The aim of this study was to estimate the prevalence of HCV infection and to assess risky practices among MSM from 12 Brazilian cities. METHODS: This study was carried out from June to December 2016 using respondent driven sampling (RDS). Participants completed a self-administered questionnaire to collect behavioral, socioeconomic, and demographic variables. In addition, the rapid diagnostic test (RDT) for HCV was offered. Positive results were sent to Instituto Adolfo Lutz for confirmation. RESULTS: A total of 4,176 participants were recruited and 23 samples were sent for confirmation. Of these, 16 were confirmed, resulting in a prevalence of 0.7% (95% CI: 0.3%-1.7%). The Southeast region showed a prevalence of 0.9% (95% CI: 0.3-2.6), followed by the South region, with 0.6% (95% CI: 0.2-2.1). The Northeast region had a prevalence of 0.3% (95% CI: 0.1-1.0) and the Midwest 0.1% (95% CI: 0.0-0.7). No positive cases were found in the North. Single men aged 40 years or older were the majority of participants exposed to HCV. High levels of alcohol consumption, illicit drug use, irregular condom use, in addition to infection with other STIs, were associated with exposure to HCV. CONCLUSIONS: STIs continue to be important health problems in Brazil and globally. Many STIs are inapparent for many years until they bring more serious consequences. Extra investment in HCV is also warranted, given that it can be eliminated. Relying solely on clinical data to provide information about inapparent infection, especially in stigmatized populations, will make that goal more difficult to achieve. Surveillance studies, such as the one reported here need to be repeated over time to demonstrate trends and to provide information for evaluation, program and policies. Investments in the most vulnerable populations are critical to achieve the World Health Organization global health goals including the elimination of viral hepatitis by 2030.

Selective reduction of CO to acetaldehyde with CuAg electrocatalysts.

Electrochemical CO reduction can serve as a sequential step in the transformation of CO2 into multicarbon fuels and chemicals. In this study, we provide insights on how to steer selectivity for CO reduction almost exclusively toward a single multicarbon oxygenate by carefully controlling the catalyst composition and its surrounding reaction conditions. Under alkaline reaction conditions, we demonstrate that planar CuAg electrodes can reduce CO to acetaldehyde with over 50% Faradaic efficiency and over 90% selectivity on a carbon basis at a modest electrode potential of -0.536 V vs. the reversible hydrogen electrode. The Faradaic efficiency to acetaldehyde was further enhanced to 70% by increasing the roughness factor of the CuAg electrode. Density functional theory calculations indicate that Ag ad-atoms on Cu weaken the binding energy of the reduced acetaldehyde intermediate and inhibit its further reduction to ethanol, demonstrating that the improved selectivity to acetaldehyde is due to the electronic effect from Ag incorporation. These findings will aid in the design of catalysts that are able to guide complex reaction networks and achieve high selectivity for the desired product.

Associations Between Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Variants and Risk of Coronavirus Disease 2019 (COVID-19) Hospitalization Among Confirmed Cases in Washington State: A Retrospective Cohort Study.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic is dominated by variant viruses; the resulting impact on disease severity remains unclear. Using a retrospective cohort study, we assessed the hospitalization risk following infection with 7 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants. METHODS: Our study includes individuals with positive SARS-CoV-2 reverse transcription polymerase chain reaction (RT-PCR) in the Washington Disease Reporting System with available viral genome data, from 1 December 2020 to 14 January 2022. The analysis was restricted to cases with specimens collected through sentinel surveillance. Using a Cox proportional hazards model with mixed effects, we estimated hazard ratios (HR) for hospitalization risk following infection with a variant, adjusting for age, sex, calendar week, and vaccination. RESULTS: In total, 58 848 cases were sequenced through sentinel surveillance, of which 1705 (2.9%) were hospitalized due to COVID-19. Higher hospitalization risk was found for infections with Gamma (HR 3.20, 95% confidence interval [CI] 2.40-4.26), Beta (HR 2.85, 95% CI 1.56-5.23), Delta (HR 2.28 95% CI 1.56-3.34), or Alpha (HR 1.64, 95% CI 1.29-2.07) compared to infections with ancestral lineages; Omicron (HR 0.92, 95% CI .56-1.52) showed no significant difference in risk. Following Alpha, Gamma, or Delta infection, unvaccinated patients show higher hospitalization risk, while vaccinated patients show no significant difference in risk, both compared to unvaccinated, ancestral lineage cases. Hospitalization risk following Omicron infection is lower with vaccination. CONCLUSIONS: Infection with Alpha, Gamma, or Delta results in a higher hospitalization risk, with vaccination attenuating that risk. Our findings support hospital preparedness, vaccination, and genomic surveillance.

Alpha- and Beta-thalassemia: Rapid Evidence Review.

Thalassemia is a group of autosomal recessive hemoglobinopathies affecting the production of normal alpha- or beta-globin chains that comprise hemoglobin. Ineffective production of alpha- or beta-globin chains may result in ineffective erythropoiesis, premature red blood cell destruction, and anemia. Chronic, severe anemia in patients with thalassemia may result in bone marrow expansion and extramedullary hematopoiesis. Thalassemia should be suspected in patients with microcytic anemia and normal or elevated ferritin levels. Hemoglobin electrophoresis may reveal common characteristics of different thalassemia subtypes, but genetic testing is required to confirm the diagnosis. Thalassemia is generally asymptomatic in trait and carrier states. Alpha-thalassemia major results in hydrops fetalis and is often fatal at birth. Beta-thalassemia major requires lifelong transfusions starting in early childhood (often before two years of age). Alpha- and beta-thalassemia intermedia have variable presentations based on gene mutation or deletion, with mild forms requiring only monitoring but more severe forms leading to symptomatic anemia and requiring transfusion. Treatment of thalassemia includes transfusions, iron chelation therapy to correct iron overload (from hemolytic anemia, intestinal iron absorption, and repeated transfusions), hydroxyurea, hematopoietic stem cell transplantation, and luspatercept. Thalassemia complications arise from bone marrow expansion, extramedullary hematopoiesis, and iron deposition in peripheral tissues. These complications include morbidities affecting the skeletal system, endocrine organs, heart, and liver. Life expectancy of those with thalassemia has improved dramatically over the past 50 years with increased availability of blood transfusions and iron chelation therapy, and improved iron overload monitoring. Genetic counseling and screening in high-risk populations can assist in reducing the prevalence of thalassemia.

Myogenic Cell Expression of Intercellular Adhesion Molecule-1 Contributes to Muscle Regeneration after Injury.

This study investigated intercellular adhesion molecule-1 (ICAM-1), a membrane protein that mediates cell-to-cell adhesion and communication, as a mechanism through which the inflammatory response facilitates muscle regeneration after injury. Toxin-induced muscle injury to tibialis anterior muscles of wild-type mice caused ICAM-1 to be expressed by a population of satellite cells/myoblasts and myofibers. Myogenic cell expression of ICAM-1 contributed to the restoration of muscle structure after injury, as regenerating myofibers were more abundant and myofiber size was larger for wild-type compared with Icam1-/- mice during 28 days of recovery. Contrastingly, restoration of muscle function after injury was similar between the genotypes. ICAM-1 facilitated the restoration of muscle structure after injury through mechanisms involving the regulation of myofiber branching, protein synthesis, and the organization of nuclei within myofibers after myogenic cell fusion. These findings provide support for a paradigm in which ICAM-1 expressed by myogenic cells after muscle injury augments their adhesive and fusogenic properties, which, in turn, facilitates regenerative and hypertrophic processes that restore structure to injured muscle.

Fractionating the all-or-nothing definition of goal-directed and habitual decision-making.

Goal-directed and habitual decision-making are fundamental processes that support the ongoing adaptive behavior. There is a growing interest in examining their disruption in psychiatric disease, often with a focus on a disease shifting control from one process to the other, usually a shift from goal-directed to habitual control. However, several different experimental procedures can be used to probe whether decision-making is under goal-directed or habitual control, including outcome devaluation and contingency degradation. These different experimental procedures may recruit diverse behavioral and neural processes. Thus, there are potentially many opportunities for these disease phenotypes to manifest as alterations to both goal-directed and habitual controls. In this review, we highlight the examples of behavioral and neural circuit divergence and similarity, and suggest that interpretation based on behavioral processes recruited during testing may leave more room for goal-directed and habitual decision-making to coexist. Furthermore, this may improve our understanding of precisely what the involved neural mechanisms underlying aspects of goal-directed and habitual behavior are, as well as how disease affects behavior and these circuits.

Cladocopium community divergence in two Acropora coral hosts across multiple spatial scales.

Many broadly-dispersing corals acquire their algal symbionts (Symbiodiniaceae) "horizontally" from their environment upon recruitment. Horizontal transmission could promote coral fitness across diverse environments provided that corals can associate with divergent algae across their range and that these symbionts exhibit reduced dispersal potential. Here we quantified community divergence of Cladocopium algal symbionts in two coral host species (Acropora hyacinthus, Acropora digitifera) across two spatial scales (reefs on the same island, and between islands) across the Micronesian archipelago using microsatellites. We find that both hosts associated with a variety of multilocus genotypes (MLG) within two genetically distinct Cladocopium lineages (C40, C21), confirming that Acropora coral hosts associate with a range of Cladocopium symbionts across this region. Both C40 and C21 included multiple asexual lineages bearing identical MLGs, many of which spanned host species, reef sites within islands, and even different islands. Both C40 and C21 exhibited moderate host specialization and divergence across islands. In addition, within every island, algal symbiont communities were significantly clustered by both host species and reef site, highlighting that coral-associated Cladocopium communities are structured across small spatial scales and within hosts on the same reef. This is in stark contrast to their coral hosts, which never exhibited significant genetic divergence between reefs on the same island. These results support the view that horizontal transmission could improve local fitness for broadly dispersing Acropora coral species.

Practice Variation in Vena Cava Filter Use Among Trauma Centers in the National Trauma Database.

BACKGROUND: Agreement regarding indications for vena cava filter (VCF) utilization in trauma patients has been in flux since the filter's introduction. As VCF technology and practice guidelines have evolved, the use of VCF in trauma patients has changed. This study examines variation in VCF placement among trauma centers. MATERIALS AND METHODS: A retrospective study was performed using data from the National Trauma Data Bank (2005-2014). Trauma centers were grouped according to whether they placed VCFs during the study period (VCF+/VCF-). A multivariable probit regression model was fit to predict the number of VCFs used among the VCF+ centers (the expected [E] number of VCF per center). The ratio of observed VCF placement (O) to expected VCFs (O:E) was computed and rank ordered to compare interfacility practice variation. RESULTS: In total, 65,482 VCFs were placed by 448 centers. Twenty centers (4.3%) placed no VCFs. The greatest predictors of VCF placement were deep vein thrombosis, spinal cord paralysis, and major procedure. The strongest negative predictor of VCF placement was admission during the year 2014. Among the VCF+ centers, O:E varied by nearly 500%. One hundred fifty centers had an O:E greater than one. One hundred sixty-nine centers had an O:E less than one. CONCLUSIONS: Substantial variation in practice is present in VCF placement. This variation cannot be explained only by the characteristics of the patients treated at these centers but could be also due to conflicting guidelines, changing evidence, decreasing reimbursement rates, or the culture of trauma centers.

Engineering Cu surfaces for the electrocatalytic conversion of CO2: Controlling selectivity toward oxygenates and hydrocarbons.

In this study we control the surface structure of Cu thin-film catalysts to probe the relationship between active sites and catalytic activity for the electroreduction of CO2 to fuels and chemicals. Here, we report physical vapor deposition of Cu thin films on large-format (∼6 cm2) single-crystal substrates, and confirm epitaxial growth in the <100>, <111>, and <751> orientations using X-ray pole figures. To understand the relationship between the bulk and surface structures, in situ electrochemical scanning tunneling microscopy was conducted on Cu(100), (111), and (751) thin films. The studies revealed that Cu(100) and (111) have surface adlattices that are identical to the bulk structure, and that Cu(751) has a heterogeneous kinked surface with (110) terraces that is closely related to the bulk structure. Electrochemical CO2 reduction testing showed that whereas both Cu(100) and (751) thin films are more active and selective for C-C coupling than Cu(111), Cu(751) is the most selective for >2e- oxygenate formation at low overpotentials. Our results demonstrate that epitaxy can be used to grow single-crystal analogous materials as large-format electrodes that provide insights on controlling electrocatalytic activity and selectivity for this reaction.

Pretest and Posttest Evaluation of a Longitudinal, Residency-Integrated Microsurgery Course.

INTRODUCTION: Current microsurgical training courses average 5 consecutive 8-hour days and cost US $1500 to US $2500/individual, making training a challenge for residents who are unable to take leave from clinical duties. This residency-integrated microsurgery course was designed for integration with a residency program, averaging 3 hours/week over 7 weeks. This allows for one-on-one training, beginning with synthetic tissue and concluding with in vivo stimulation. This study was performed to validate this longitudinal training course. METHODS: After recruitment and before the start of coursework, subjects completed a baseline anastomosis without guidance and a survey regarding microsurgical experience. Subjects completed approximately 3 hours/week of practical exercises. Weeks 1 to 5 used synthetic models, whereas 6 to 7 used in vivo rodent models. Nine minimum anastomoses of increasing complexity were completed and assessed with the Anastomosis Lapse Index and the Stanford Microsurgery and Residency Training scale. Scoring was performed by 3 independent reviewers and averaged for comparison. RESULTS: Five subjects completed the course for study. Presurvey results showed an average confidence in theoretical knowledge of 2/5; technical ability to perform procedures, 1.8/5; and ability to manage complications, 1.8/5. Postsurvey revealed confidence in theoretical knowledge of 2.5/5; technical ability to perform procedures, 2.25/5; and ability to manage complications, 2.25/5. None of these differences were significant. Each individual component of the Stanford Microsurgery and Residency Training scale scoring system improved postcourse with P < 0.05, and overall performance score improved from an average of 2.6 to 3.9 (P = 0.006). The total number of errors recorded using the Anastomosis Lapse Index reduced from 6.58 to 3.41 (P = 0.02). Time to completion reduced from an average of 28 minutes, 8 seconds to 24 minutes, 5 seconds (P = 0.003). CONCLUSIONS: Despite a lack in significant confidence improvement, completion of the residency-integrated microsurgery course leads to significant and quantifiable improvement in resident microsurgical skill and efficiency.

Innovative learning in pharmacy practice: The perceived benefits of and barriers to a layered learning practice model.

OBJECTIVE: To assess pharmacy preceptors' perceptions of the benefits of and barriers to a layered learning practice model (LLPM) at their practice site. METHODS: An online survey was created using Qualtrics and sent to experiential directors at all colleges [or schools] of pharmacy in Ohio and at Big Ten universities. The experiential directors were asked to send the survey to all preceptors affiliated with their program. The survey assessed the perceived or actual benefits of and barriers to a layered learning model. Benefits and barriers to patient care, student or resident learning, and the practice site were assessed. RESULTS: In total, 304 surveys were initiated by precepting pharmacists. Survey respondents reported precepting introductory pharmacy practice experience students (n = 113, 37.1%), advanced pharmacy practice experience students (n = 184, 60.5%), and residents (n = 176, 57.9%) throughout a given year. Survey respondents' most commonly identified benefits of a LLPM included an increase in patient access to pharmacy team members (n = 97, 42.3%), an increase in the number of precepting opportunities for learners (n = 80, 34.9%), and improvement in patient education (n = 76, 33.2%). The top identified barriers to a LLPM included performing precepting duties that may interfere with preceptor job responsibilities (n = 158, 72.1%), having inadequate workspace for learners (n = 120, 54.8%), and being unable to effectively teach or oversee multiple learners simultaneously (n = 77, 35.1%). CONCLUSIONS: This research provides insight into pharmacy preceptor perception of how a LLPM impacts practice sites, patient care, and training of pharmacy learners. This information may be valuable in the design of preceptor development for colleges of pharmacy and residency programs.

Understanding the Origin of Highly Selective CO2 Electroreduction to CO on Ni,N-doped Carbon Catalysts.

Ni,N-doped carbon catalysts have shown promising catalytic performance for CO2 electroreduction (CO2 R) to CO; this activity has often been attributed to the presence of nitrogen-coordinated, single Ni atom active sites. However, experimentally confirming Ni-N bonding and correlating CO2 reduction (CO2 R) activity to these species has remained a fundamental challenge. We synthesized polyacrylonitrile-derived Ni,N-doped carbon electrocatalysts (Ni-PACN) with a range of pyrolysis temperatures and Ni loadings and correlated their electrochemical activity with extensive physiochemical characterization to rigorously address the origin of activity in these materials. We found that the CO2 R to CO partial current density increased with increased Ni content before plateauing at 2 wt % which suggests a dispersed Ni active site. These dispersed active sites were investigated by hard and soft X-ray spectroscopy, which revealed that pyrrolic nitrogen ligands selectively bind Ni atoms in a distorted square-planar geometry that strongly resembles the active sites of molecular metal-porphyrin catalysts.

Unsupervised machine learning reveals mimicry complexes in bumblebees occur along a perceptual continuum.

Müllerian mimicry theory states that frequency-dependent selection should favour geographical convergence of harmful species onto a shared colour pattern. As such, mimetic patterns are commonly circumscribed into discrete mimicry complexes, each containing a predominant phenotype. Outside a few examples in butterflies, the location of transition zones between mimicry complexes and the factors driving mimicry zones has rarely been examined. To infer the patterns and processes of Müllerian mimicry, we integrate large-scale data on the geographical distribution of colour patterns of social bumblebees across the contiguous United States and use these to quantify colour pattern mimicry using an innovative, unsupervised machine-learning approach based on computer vision. Our data suggest that bumblebees exhibit geographically clustered, but sometimes imperfect colour patterns, and that mimicry patterns gradually transition spatially rather than exhibit discrete boundaries. Additionally, examination of colour pattern transition zones of three comimicking, polymorphic species, where active selection is driving phenotype frequencies, revealed that their transition zones differ in location within a broad region of poor mimicry. Potential factors influencing mimicry transition zone dynamics are discussed.

Toilet Training: Common Questions and Answers.

Toilet training is a significant developmental milestone in early childhood. Most U.S. children achieve the physiologic, cognitive, and emotional development necessary for toilet training by 18 to 30 months of age. Markers of readiness for toilet training include being able to walk, put on and remove clothing, and follow parental instruction; expressive language; awareness of a full bladder or rectum; and demonstrated dissatisfaction with a soiled diaper. Other readiness cues include imitating toileting behavior, expressing desire to toilet, and demonstrating bladder or bowel control (staying dry through a nap or through the night). Physicians should provide anticipatory guidance to parents beginning at about 18 to 24 months of age, noting the signs of toilet training readiness, and setting realistic expectations for parents. Parents should be counseled that no training method is superior to another. Parents should choose a method that is best suited to them and their child, and the method should use positive reinforcement. Complications of toilet training include stool toileting refusal, stool withholding, encopresis, hiding to defecate, and enuresis. These problems typically resolve with time, although some may require further investigation and treatment. Medical comorbidities such as Down syndrome, autism spectrum disorder, and cerebral palsy reduce the likelihood of successfully attaining full toilet training and often require early consultation with occupational therapists, developmental pediatricians, or other subspecialists to aid in toilet training.