An Internship Approach to Strengthen the Pathway for Historically Underrepresented Groups in Health Sciences Research: The North Carolina Diversity and Inclusion Pathway Program.

BACKGROUND: To increase engagement of historically underrepresented groups in health sciences research, we created the North Carolina Diversity and Inclusion Pathway Program (NC-DIPP). This year-long, paid internship provides undergraduate and graduate students from 2 historically Black colleges and universities an opportunity to gain real-world experience under the mentorship of expert faculty. METHODS: To evaluate the early experiences with the NC-DIPP program, we conducted semi-structured interviews with interns and program leaders. Faculty mentors completed an online questionnaire to describe their experiences to date. A thematic approach was used to analyze the findings. RESULTS: In March-April 2023, 7 of 8 interns (88%), 6 of 11 mentors (54%), and 4 of 4 program leaders (100%) participated in various evaluation components. Overall, respondents agreed about the importance of programs like NC-DIPP, which further engage historically underrepresented groups in the health sciences. Interns had positive feedback about the internship, including real-world work experience, connections to experienced mentors, and early career planning. On a scale of 1 (poor) to 10 (excellent), interns rated their experience as a median of 8.3 (range: 4.5-10.0). Mentors had favorable but slightly lower scores (median: 7.0, range: 5.0-8.0). Areas for improvement were noted, including clearer expectations, improved logistical support, and central engagement of interns across projects. CONCLUSIONS: This early evaluation of NC-DIPP was generally favorable across all stakeholder groups. By providing a long-term experience in health science research, such programs can contribute to work experience, career planning, and professional networking.

Evidence of Antineutrinos from Distant Reactors Using Pure Water at SNO.

The SNO+ Collaboration reports the first evidence of reactor antineutrinos in a Cherenkov detector. The nearest nuclear reactors are located 240 km away in Ontario, Canada. This analysis uses events with energies lower than in any previous analysis with a large water Cherenkov detector. Two analytical methods are used to distinguish reactor antineutrinos from background events in 190 days of data and yield consistent evidence for antineutrinos with a combined significance of 3.5σ.

Elamipretide mitigates ischemia-reperfusion injury in a swine model of hemorrhagic shock.

ischemia-reperfusion injury (IRI) after hemorrhage is potentiated by aortic occlusion or resuscitative endovascular balloon occlusion of the aorta (REBOA). Given the central role of mitochondrial injury in shock, we hypothesized that Elamipretide, a peptide that protects mitochondria, would mitigate IRI after hemorrhagic shock and REBOA. Twelve pigs were subjected to hemorrhagic shock and 45 min of REBOA. After 25 min of REBOA, animals received either saline or Elamipretide. Animals were transfused with autologous blood during balloon deflation, and pigs were resuscitated with isotonic crystalloids and norepinephrine for 4.25 h. Elamipretide-treated animals required less crystalloids than the controls (62.5 [50-90] and 25 [5-30] mL/kg, respectively), but similar amounts of norepinephrine (24.7 [8.6-39.3] and 9.7 [2.1-12.5] mcg/kg, respectively). Treatment animals had a significant reduction in serum creatinine (control: 2.7 [2.6-2.8]; Elamipretide: 2.4 [2.4-2.5] mg/dL; p = 0.04), troponin (control: 3.20 [2.14-5.47] ng/mL, Elamipretide: 0.22 [0.1-1.91] ng/mL; p = 0.03), and interleukin-6 concentrations at the end of the study. There were no differences in final plasma lactate concentration. Elamipretide reduced fluid requirements and protected the kidney and heart after profound IRI. Further understanding the subcellular consequences of REBOA and mitochondrial rescue will open new therapeutic avenues for patients suffering from IRI after hemorrhage.

MiniBooNE and MicroBooNE Combined Fit to a 3+1 Sterile Neutrino Scenario.

This Letter presents the results from the MiniBooNE experiment within a full "3+1" scenario where one sterile neutrino is introduced to the three-active-neutrino picture. In addition to electron-neutrino appearance at short baselines, this scenario also allows for disappearance of the muon-neutrino and electron-neutrino fluxes in the Booster Neutrino Beam, which is shared by the MicroBooNE experiment. We present the 3+1 fit to the MiniBooNE electron-(anti)neutrino and muon-(anti)neutrino data alone and in combination with MicroBooNE electron-neutrino data. The best-fit parameters of the combined fit with the exclusive charged-current quasielastic analysis (inclusive analysis) are Δm^{2}=0.209 eV^{2}(0.033 eV^{2}), |U_{e4}|^{2}=0.016(0.500), |U_{µ4}|^{2}=0.500(0.500), and sin^{2}(2θ_{µe})=0.0316(1.0). Comparing the no-oscillation scenario to the 3+1 model, the data prefer the 3+1 model with a Δχ^{2}/d.o.f.=24.7/3(17.3/3), a 4.3σ(3.4σ) preference assuming the asymptotic approximation given by Wilks's theorem.

Exploring fungal RiPPs from the perspective of chemical ecology.

Since the initial detection, in 2007, of fungal ribosomally synthesised and post-translationally modified peptides (RiPPs), this group of natural products has undergone rapid expansion, with four separate classes now recognised: amatoxins/phallotoxins, borosins, dikaritins, and epichloëcyclins. Largely due to their historically anthropocentric employment in medicine and agriculture, novel fungal proteins and peptides are seldom investigated in relation to the fungus itself. Therefore, although the benefits these compounds confer to humans are often realised, their evolutionary advantage to the fungus, the reason for their continued production, is often obscure or ignored. This review sets out to summarise current knowledge on how these small peptide-derived products influence their producing species and surrounding biotic environment.

Electrolysis outcomes for eyelid trichiasis: Consultants versus trainees.

PURPOSE: To investigate the efficacy of electrolysis for the treatment of trichiasis and distichiasis and compare success rates as a function of the eyelid treated, the indication for electrolysis and seniority of the surgeon. METHODS: The medical records of all patients who underwent electrolysis for trichiasis or distichiasis from November 2015 to November 2020 were reviewed. Sex, age, indication, eyelid treated, surgeon's educational status, number of electrolysis sessions, outcome, time between sessions and time to the last follow-up were documented. RESULTS: In total, 187 patients who underwent primary electrolysis during the study period and no prior history of trichiasis treatment were included in the analysis. Attending physicians had a significantly higher success rate after the first electrolysis session than resident surgeons (P=0.048). The success rate for patients receiving treatment of their upper or upper and lower eyelids at the same time was significantly lower than the respective percentage of patients receiving treatment of their lower eyelids (P=0.005). CONCLUSION: Improved departmental efficiency could be achieved by scheduling patients with recurrent trichiasis or distichiasis, especially of their upper eyelids, after electrolysis with an attending physician. Furthermore, improved training for ophthalmology residents in electrolysis indications and techniques would be useful.

International links between Streptococcus pneumoniae vaccine serotype 4 sequence type (ST) 801 in Northern European shipyard outbreaks of invasive pneumococcal disease.

BACKGROUND: Pneumococcal disease outbreaks of vaccine preventable serotype 4 sequence type (ST)801 in shipyards have been reported in several countries. We aimed to use genomics to establish any international links between them. METHODS: Sequence data from ST801-related outbreak isolates from Norway (n = 17), Finland (n = 11) and Northern Ireland (n = 2) were combined with invasive pneumococcal disease surveillance from the respective countries, and ST801-related genomes from an international collection (n = 41 of > 40,000), totalling 106 genomes. Raw data were mapped and recombination excluded before phylogenetic dating. RESULTS: Outbreak isolates were relatively diverse, with up to 100 SNPs (single nucleotide polymorphisms) and a common ancestor estimated around the year 2000. However, 19 Norwegian and Finnish isolates were nearly indistinguishable (0-2 SNPs) with the common ancestor dated around 2017. CONCLUSION: The total diversity of ST801 within the outbreaks could not be explained by recent transmission alone, suggesting that harsh environmental and associated living conditions reported in the shipyards may facilitate invasion of colonising pneumococci. However, near identical strains in the Norwegian and Finnish outbreaks does suggest that transmission between international shipyards also contributed to those outbreaks. This indicates the need for improved preventative measures in this working population including pneumococcal vaccination.

Pulse-shape discrimination against low-energy Ar-39 beta decays in liquid argon with 4.5 tonne-years of DEAP-3600 data.

The DEAP-3600 detector searches for the scintillation signal from dark matter particles scattering on a 3.3 tonne liquid argon target. The largest background comes from 39 Ar beta decays and is suppressed using pulse-shape discrimination (PSD). We use two types of PSD estimator: the prompt-fraction, which considers the fraction of the scintillation signal in a narrow and a wide time window around the event peak, and the log-likelihood-ratio, which compares the observed photon arrival times to a signal and a background model. We furthermore use two algorithms to determine the number of photons detected at a given time: (1) simply dividing the charge of each PMT pulse by the mean single-photoelectron charge, and (2) a likelihood analysis that considers the probability to detect a certain number of photons at a given time, based on a model for the scintillation pulse shape and for afterpulsing in the light detectors. The prompt-fraction performs approximately as well as the log-likelihood-ratio PSD algorithm if the photon detection times are not biased by detector effects. We explain this result using a model for the information carried by scintillation photons as a function of the time when they are detected.

Spreadsheet Tools for Quantifying Seepage Flux Across the GW-SW Interface.

Identifying the spatial distribution and magnitude of seepage flux across the groundwater-surface water (GW-SW) interface is critical for assessing potential impairments and restoration alternatives for water bodies adjacent to sites with groundwater contamination. Measurement of the vertical distribution and time-varying characteristics of temperature in sediments provides an indirect way to map out spatial and temporal patterns of seepage flux into surface water. Two spreadsheet-based calculation tools are introduced that implement four one-dimensional analytical solutions to calculate the magnitude and direction of seepage flux based on measurement of steady-state vertical temperature profiles or transient diel temperature signals at two depths within sediment. Performance of these calculation tools is demonstrated for a pond receiving contaminated groundwater discharge from an adjacent landfill. Transient versus steady-state model performance is compared, and limitations of transient modelsare illustrated for a situation with unfavorable sediment characteristics and inadequate sensor spacing. The availability of a range of analytical solutions implemented within Microsoft Excel® is intended to encourage practitioners to explore use of this seepage flux characterization method and develop greater insight into best practices for model selection and use.

Evaluation of the fate of carcasses and dummies deployed in the nearshore and offshore waters of the northern Gulf of Mexico.

In response to the Deepwater Horizon oil spill, federal and state agencies conducted field studies to develop inputs for a shoreline deposition model used to estimate nearshore avian mortality resulting from the spill. A 2011 carcass drift study was designed to generate data on the likelihood that birds that died on the water would deposit along the northern Gulf of Mexico coast (rather than becoming lost at sea). In the case of the Deepwater Horizon oil spill, carcass losses at sea accounted for a significant portion of nearshore avian mortality. We evaluate the data collected during the Deepwater Horizon carcass drift study and compare the results obtained from the use of avian carcasses versus dummy carcasses (dummies) and the differences between those deployed nearshore versus further offshore. We conclude that, although the use of dummies provided valuable confirmation on the drift patterns of dead birds, dummies drifted greater distances, for longer periods of time, and were more likely to be observed beached compared to avian carcasses, with 64.6% of dummies beaching compared to 17.2% of carcasses. In response to future spills, researchers should account for these potential biases when incorporating dummy drift data into estimates of avian carcass loss. Further, none of the avian carcasses and dummies released more than 40 km from the shoreline made it to shore. In the northern Gulf of Mexico, carcasses that die on the waters farther offshore are unlikely to make it to shore to be captured in a deposition model; therefore, it may be appropriate to utilize a separate methodology to estimate offshore mortality. The applicability of these results to other spill events should be evaluated in the context of the specific spill characteristics.

Using a mark-recapture model to estimate beaching probability of seabirds killed in nearshore waters during the Deepwater Horizon oil spill.

During a marine oil spill, injured birds often die on the water, some eventually washing ashore, but others becoming waterlogged and sinking or being scavenged before reaching the shoreline. Birds that disappear before they can be deposited on the shoreline are difficult to enumerate, but they commonly represent a large fraction of total oil spill-related mortality. As part of the process of quantifying the overall impact to seabirds resulting from the Deepwater Horizon oil spill, it was necessary to estimate the number of dead birds lost at sea. We conducted a study to estimate the beaching probability of birds that died at sea in the Gulf of Mexico in the areas most heavily used by seabirds and impacted by the spill. Using a mark-recapture analysis to derive the beaching probability from our field study data, we estimated that dead birds afloat at sea had about a 0.1414 probability of beaching in areas searched during the Deepwater Horizon oil spill. Sensitivity analyses of our model and requisite assumptions suggested that if our assumptions were violated, the "true" beaching probability could be anywhere between 0.11 and 0.16. These estimates are much lower than beaching probabilities estimated for seabirds killed during the Exxon Valdez oil spill in the waters of Alaska, for example, likely reflect higher rates of decomposition and scavenging in the warmer waters of the Gulf of Mexico. Our estimate suggests that bird carcasses that washed onshore during the Deepwater Horizon oil spill represented only 14% of those killed at sea during the spill.

Significant Excess of Electronlike Events in the MiniBooNE Short-Baseline Neutrino Experiment.

The MiniBooNE experiment at Fermilab reports results from an analysis of ν_{e} appearance data from 12.84×10^{20} protons on target in neutrino mode, an increase of approximately a factor of 2 over previously reported results. A ν_{e} charged-current quasielastic event excess of 381.2±85.2 events (4.5σ) is observed in the energy range 200

First Results from the DEAP-3600 Dark Matter Search with Argon at SNOLAB.

This Letter reports the first results of a direct dark matter search with the DEAP-3600 single-phase liquid argon (LAr) detector. The experiment was performed 2 km underground at SNOLAB (Sudbury, Canada) utilizing a large target mass, with the LAr target contained in a spherical acrylic vessel of 3600 kg capacity. The LAr is viewed by an array of PMTs, which would register scintillation light produced by rare nuclear recoil signals induced by dark matter particle scattering. An analysis of 4.44 live days (fiducial exposure of 9.87 ton day) of data taken during the initial filling phase demonstrates the best electronic recoil rejection using pulse-shape discrimination in argon, with leakage <1.2×10^{-7} (90% C.L.) between 15 and 31 keV_{ee}. No candidate signal events are observed, which results in the leading limit on weakly interacting massive particle (WIMP)-nucleon spin-independent cross section on argon, <1.2×10^{-44} cm^{2} for a 100 GeV/c^{2} WIMP mass (90% C.L.).

First Measurement of Monoenergetic Muon Neutrino Charged Current Interactions.

We report the first measurement of monoenergetic muon neutrino charged current interactions. MiniBooNE has isolated 236 MeV muon neutrino events originating from charged kaon decay at rest (K^{+}→µ^{+}ν_{µ}) at the NuMI beamline absorber. These signal ν_{µ}-carbon events are distinguished from primarily pion decay in flight ν_{µ} and ν[over ¯]_{µ} backgrounds produced at the target station and decay pipe using their arrival time and reconstructed muon energy. The significance of the signal observation is at the 3.9σ level. The muon kinetic energy, neutrino-nucleus energy transfer (ω=E_{ν}-E_{µ}), and total cross section for these events are extracted. This result is the first known-energy, weak-interaction-only probe of the nucleus to yield a measurement of ω using neutrinos, a quantity thus far only accessible through electron scattering.

Comparing assessment tools for detecting undernutrition in patients with liver cirrhosis.

BACKGROUND AND AIMS: Undernutrition in cirrhotic patients is often poorly recognised until late-stages. The current UK screening tool, the Malnutrition Universal Screening Tool, can miss undernutrition in patients with ascites/fluid retention. A 6-question Liver Disease Undernutrition Screening Tool (LDUST) has been developed in America. METHODS: We sought to compare LDUST with MUST in the detection of undernutrition in 50 inpatients and 50 outpatients with liver cirrhosis in a secondary care setting. This was then validated by a dietitian assessment. RESULTS: Similar patient demographics and liver disease aetiologies were found in the two cohorts. Mean Child-Pugh scores were higher for inpatients, 8.3 (SD 1.9) vs 5.9 (SD 1.2). LDUST detected undernutrition in 45/50 inpatients (90%) and 34/50 outpatients (68%). MUST scores ≥2 were present in 19/50 (38%) inpatients and 9/50 (18%) outpatients. In those with a MUST score <2, LDUST detected undernutrition in 26/31 (84%) inpatients and 27/41 (66%) outpatients. 26 inpatients had undernutrition using LDUST but had a MUST score <2, 20 (76%) of these were deemed to be undernourished by dietetics assessment. LDUST was mostly completed independently or with minimal assistance (80% inpatients, 100% outpatients), with mean completion times of 4 and 3 min for in- and outpatients respectively. CONCLUSION: LDUST is a quick and easy screening tool, which appears better able than MUST to detect undernutrition in cirrhotic patients, including undernutrition missed by MUST. Importantly the tool was validated against dietitian assessments. The high rates of undernutrition among cirrhotic inpatients suggest that screening this cohort is unnecessary, and instead all should undergo dietitian review, with LDUST utilised in an outpatient setting.

Dark Matter Search in a Proton Beam Dump with MiniBooNE.

The MiniBooNE-DM Collaboration searched for vector-boson mediated production of dark matter using the Fermilab 8-GeV Booster proton beam in a dedicated run with 1.86×10^{20} protons delivered to a steel beam dump. The MiniBooNE detector, 490 m downstream, is sensitive to dark matter via elastic scattering with nucleons in the detector mineral oil. Analysis methods developed for previous MiniBooNE scattering results were employed, and several constraining data sets were simultaneously analyzed to minimize systematic errors from neutrino flux and interaction rates. No excess of events over background was observed, leading to a 90% confidence limit on the dark matter cross section parameter, Y=ε^{2}α_{D}(m_{χ}/m_{V})^{4}≲10^{-8}, for α_{D}=0.5 and for dark matter masses of 0.01

Treatment of HCV infection in liver transplant recipients with ledipasvir and sofosbuvir without ribavirin.

BACKGROUND: Ledipasvir and sofosbuvir is a well-tolerated regimen with high sustained virological response (SVR) rates in pre-liver transplant patients infected with chronic hepatitis C virus (HCV), but data in liver transplant recipients outside of clinical trials is limited. AIM: To address this knowledge gap and assess SVR rates without the use of ribavirin in liver transplant recipients METHODS: This is a retrospective study examining the treatment of 75 post-liver transplant recipients with ledipasvir and sofosbuvir without ribavirin. Differences between SVR cohorts and predictors of SVR were analysed in an intention-to-treat (ITT) fashion. RESULTS: A total of 408 genotype 1, HCV patients were treated with ledipasvir/sofosbuvir from October 2014 to August 2015 at our centre. Seventy-three patients were post-liver transplant and were treated with a median of 2.9 years from transplant. Ledipasvir/sofosbuvir achieved an SVR12 of 95.9%. African Americans made up 28.8% of the cohort. Sixty-three per cent of patients were treated previously, including 13.7% of patients previously treated with direct-acting antivirals. Only 2.7% had recurrent allograft cirrhosis, and the majority (90.4%) was on calcineurin inhibitor based immunosuppressive therapy. Approximately 82% of patients had chronic kidney disease (CKD) stage 2 or 3. In univariate logistic regression, only detectable week 8 viral load was predictive of failure to achieve SVR. CONCLUSION: Our data confirm excellent SVR outcomes and favourable safety and tolerability profiles with ledipasvir/sofosbuvir without ribavirin in post-liver transplant recipients infected with HCV, despite treatment guidelines to use ribavirin.

Success rate of nurse-led everting sutures for involutional lower lid entropion.

PurposeTo evaluate safety and long-term recurrence rate of entropion in patients having everting sutures (ES) for involutional entropion by ophthalmic nurses in a real clinical setting.Patients and methodsRetrospective notes review of all patients who had an outpatient ES by our trained ophthalmic nurses over 2 year's time period. Outcome measures were complication and recurrence rates. Those with less than 3 years' recorded follow-up were contacted by paper questionnaire.Results90 lids of 82 patients analysed. Mean age was 78 (range 54-97). In total, 82% had no entropion surgery before, whereas 13% had previous ES and 5% one or more other procedures. Questionnaires were sent to 38, with return rate of 81%. Recurrence rate was 21.1% after 36-60 months follow up from nurse-performed ES, with mean time to recurrence of 15 months (SD 13 months). A total of 32% of patients died during the follow-up period. Mean time between the procedure and death is 20.5 months. When ES were repeated twice (11 patients), recurrence rate was still 20%. No patients had any complications.ConclusionES can be safely performed by ophthalmic nurses, with success rate comparable to the same technique performed by ophthalmologists.

SymptoMScreen: A Tool for Rapid Assessment of Symptom Severity in MS Across Multiple Domains.

The objective of this study was to describe SymptoMScreen, an in-house developed tool for rapid assessment of MS symptom severity in routine clinical practice, and to validate SymptoMScreen against Performance Scales (PS). MS patients typically experience symptoms in many neurologic domains. A tool that would enable MS patients to efficiently relay their symptom severity across multiple domains to the healthcare providers could lead to improved symptom management. We developed "SymptoMScreen," a battery of 7-point Likert scales for 12 distinct domains commonly affected by MS: mobility, dexterity, body pain, sensation, bladder function, fatigue, vision, dizziness, cognition, depression, and anxiety. We administered SymptoMScreen and PS scales to consecutive MS patients at a specialty MS Care Center. We assessed the criterion and construct validity of SymptoMScreen by calculating Spearmen rank correlations between the SymptoMScreen composite score and PS composite score, and between SymptoMScreen subscale and the respective PS subscale scores, where applicable. A total of 410 patients with MS (age 46.6 ± 12.9 years; 74% female; mean disease duration 12.2 ± 8.7 years) completed the SymptoMScreen and PSs during their clinic visit. Composite SymptoMScreen score correlated strongly with combined PS score (r = 0.88, p < 0.0001). SymptoMScreen sub scores correlated strongly with the criterion measures of the respective PS (r = 0.69-0.87, p < 0.0001). Test-retest reliability of SymptoMScreen and its subscales was excellent (r = 0.71-0.94, p < .0001). SymptoMScreen is a single-page battery of Likert scales that assesses symptom impact in 12 domains commonly affected in MS. It has excellent criterion and construct validity. SymptoMScreen is patient and clinician friendly, takes approximately one minute to complete, and can help better document, understand, and manage patients' symptoms in routine clinical practice. SymptoMScreen is freely available to clinicians and researchers.