North Atlantic climate far more predictable than models imply.

Quantifying signals and uncertainties in climate models is essential for the detection, attribution, prediction and projection of climate change1-3. Although inter-model agreement is high for large-scale temperature signals, dynamical changes in atmospheric circulation are very uncertain4. This leads to low confidence in regional projections, especially for precipitation, over the coming decades5,6. The chaotic nature of the climate system7-9 may also mean that signal uncertainties are largely irreducible. However, climate projections are difficult to verify until further observations become available. Here we assess retrospective climate model predictions of the past six decades and show that decadal variations in North Atlantic winter climate are highly predictable, despite a lack of agreement between individual model simulations and the poor predictive ability of raw model outputs. Crucially, current models underestimate the predictable signal (the predictable fraction of the total variability) of the North Atlantic Oscillation (the leading mode of variability in North Atlantic atmospheric circulation) by an order of magnitude. Consequently, compared to perfect models, 100 times as many ensemble members are needed in current models to extract this signal, and its effects on the climate are underestimated relative to other factors. To address these limitations, we implement a two-stage post-processing technique. We first adjust the variance of the ensemble-mean North Atlantic Oscillation forecast to match the observed variance of the predictable signal. We then select and use only the ensemble members with a North Atlantic Oscillation sufficiently close to the variance-adjusted ensemble-mean forecast North Atlantic Oscillation. This approach greatly improves decadal predictions of winter climate for Europe and eastern North America. Predictions of Atlantic multidecadal variability are also improved, suggesting that the North Atlantic Oscillation is not driven solely by Atlantic multidecadal variability. Our results highlight the need to understand why the signal-to-noise ratio is too small in current climate models10, and the extent to which correcting this model error would reduce uncertainties in regional climate change projections on timescales beyond a decade.

Response-adapted anti-PD-1-based salvage therapy for Hodgkin lymphoma with nivolumab alone or in combination with ICE.

This phase 2 trial evaluated PET-adapted nivolumab alone or in combination with ifosfamide, carboplatin, and etoposide (NICE) as first salvage therapy and bridge to autologous hematopoietic cell transplantation (AHCT) in relapsed/refractory (RR) classical Hodgkin lymphoma (cHL). Patients with RR cHL received 240 mg nivolumab every 2 weeks for up to 6 cycles (C). Patients in complete response (CR) after C6 proceeded to AHCT, whereas patients with progressive disease at any point or not in CR after C6 received NICE for 2 cycles. The primary endpoint was CR rate per the 2014 Lugano classification at completion of protocol therapy. Forty-three patients were evaluable for toxicity; 42 were evaluable for response. Thirty-four patients received nivolumab alone, and 9 patients received nivolumab+NICE. No unexpected toxicities were observed after nivolumab or NICE. After nivolumab, the overall response rate (ORR) was 81%, and the CR rate was 71%. Among 9 patients who received NICE, all responded, with 8 (89%) achieving CR. At the end of protocol therapy, the ORR and CR rates were 93% and 91%. Thirty-three patients were bridged directly to AHCT, including 26 after Nivo alone. The 2-year progression-free survival (PFS) and overall survival in all treated patients (n = 43) were 72% and 95%, respectively. Among 33 patients who bridged directly to AHCT, the 2-year PFS was 94% (95% CI: 78-98). PET-adapted sequential salvage therapy with nivolumab/nivolumab+NICE was well tolerated and effective, resulting in a high CR rate and bridging most patients to AHCT without chemotherapy. This trial was registered at www.clinicaltrials.gov #NCT03016871.

Strategies for DPYD testing prior to fluoropyrimidine chemotherapy in the US.

PURPOSE: Patients with dihydropyrimidine dehydrogenase (DPD) deficiency are at high risk for severe and fatal toxicity from fluoropyrimidine (FP) chemotherapy. Pre-treatment DPYD testing is standard of care in many countries, but not the United States (US). This survey assessed pre-treatment DPYD testing approaches in the US to identify best practices for broader adoption. METHODS: From August to October 2023, a 22-item QualtricsXM survey was sent to institutions and clinicians known to conduct pre-treatment DPYD testing and broadly distributed through relevant organizations and social networks. Responses were analyzed using descriptive analysis. RESULTS: Responses from 24 unique US sites that have implemented pre-treatment DPYD testing or have a detailed implementation plan in place were analyzed. Only 33% of sites ordered DPYD testing for all FP-treated patients; at the remaining sites, patients were tested depending on disease characteristics or clinician preference. Almost 50% of sites depend on individual clinicians to remember to order testing without the assistance of electronic alerts or workflow reminders. DPYD testing was most often conducted by commercial laboratories that tested for at least the four or five DPYD variants considered clinically actionable. Approximately 90% of sites reported receiving results within 10 days of ordering. CONCLUSION: Implementing DPYD testing into routine clinical practice is feasible and requires a coordinated effort among the healthcare team. These results will be used to develop best practices for the clinical adoption of DPYD testing to prevent severe and fatal toxicity in cancer patients receiving FP chemotherapy.

Proposing a new history of grief's medicalisation: A critical discourse analysis.

Conceptualisations of grief have transformed significantly in recent decades, from an experience accepted and expressed in community spaces to a diagnosable clinical phenomenon. Narratives of this transformation tend to focus on grief's relationship to major depression, or on recent nosological changes. This paper examines the possibility of a new narrative for medicalisation by grounding in the networks of language and power created around 'grief' through a critical discourse analysis of psy-discipline articles (n = 70) published between 1975 and 1995. Focusing on shifts in definitions of, methods used to approach, and rationales motivating study of the experience, it posits that the psy-disciplines exerted exclusive expertise over grief decades before its creation as a diagnosis. By reconceptualising grief in the terms of psy-specific symptoms and functional performance and by approaching it with the decontextualising and interventionist methods of an increasingly scientific psy-discipline, the psy-community medicalised grief between 1975 and 1995. Identifying neoliberal and other cultural influences shaping this process of medical construction and reconsidering narratives of grief's history mindful of the powers exerted in medicalisation, this paper establishes that these moments played a critical role in the development of the present's grief.

Evidence Regarding Pharmacogenetics in Pain Management and Cancer.

Patients experience interindividual variation in response to analgesics, which may be partially explained by genetics. This commentary discusses a recently published trial on COMT genotype and opioid dose requirements and describes the potential role for COMT and other genes (eg, CYP2D6) on opioid therapy and the current evidence for germline pharmacogenetics and resources for opioid pharmacogenetics.

Parents' experiences of life after medicalised conception: a thematic meta-synthesis of the qualitative literature.

BACKGROUND: Medicalised Conception (MAC) assists many couples to achieve pregnancy worldwide. As the impact of MAC has been linked to increased pregnancy-specific anxiety and parenting difficulties, this review aimed to explore parental experiences of pregnancy and early parenting following MAC, identifying parents' psychological, social and health needs. METHOD: Five databases were searched systematically from inception to March 2023. Identified articles were screened for eligibility against the inclusion criteria and the results were analysed using thematic synthesis. The Critical Appraisal Skills checklist was employed to appraise methodological quality. RESULTS: Twenty qualitative studies, drawing on a total of 19 participant samples, were included in this review, most with samples with history of subfertility. The findings were synthesised into three main themes (consisting of seven subthemes): 1) The vulnerable parent: fear, doubt, uncertainty, 2) the stark realisation of the parental dream, 3) psychosocial needs and support. Parents lacked a sense of safety during pregnancy and reported acting protectively both antenatally and postnatally. Furthermore, their identity transition was complex and non-linear, influenced by sociocultural context. CONCLUSIONS: Considerable unmet psychosocial needs were identified including the potential for anxiety in pregnancy, the possibility of feeling excluded and marginalised, and a reluctance to share distress and experiences with healthcare professionals. These findings suggest a need for consistent, holistic care, integrating psychological services.

Automated Identification of Patent Ductus Arteriosus Using a Computer Vision Model.

OBJECTIVES: Patent ductus arteriosus (PDA) is a vascular defect common in preterm infants and often requires treatment to avoid associated long-term morbidities. Echocardiography is the primary tool used to diagnose and monitor PDA. We trained a deep learning model to identify PDA presence in relevant echocardiographic images. METHODS: Echocardiography video clips (n = 2527) in preterm infants were reviewed by a pediatric cardiologist and those relevant to PDA diagnosis were selected and labeled (PDA present/absent/indeterminate). We trained a convolutional neural network to classify each echocardiography frame of a clip as belonging to clips with or without PDA. A novel attention mechanism that aggregated predictions for all frames in each clip to obtain a clip-level prediction by weighting relevant frames. RESULTS: In early model iterations, we discovered training with color Doppler echocardiography clips produced the best performing classifier. For model training and validation, 1145 such clips from 66 patients (661 PDA+ clips, 484 PDA- clips) were used. Our best classifier for clip level performance obtained sensitivity of 0.80 (0.83-0.90), specificity of 0.77 (0.62-0.92) and AUC of 0.86 (0.83-0.90). Study level performance obtained sensitivity of 0.83 (0.72-0.94), specificity of 0.89 (0.79-1.0) and AUC of 0.93 (0.89-0.98). CONCLUSIONS: Our novel deep learning model demonstrated strong performance in classifying echocardiography clips with and without PDA. Further model development and external validation are warranted. Ultimately, integration of such a classifier into auto detection software could streamline PDA imaging workflow. This work is the first step toward semi-automated, bedside detection of PDA in preterm infants.

Spatial patterns of prostate-specific antigen testing in asymptomatic men across Australia: a population-based cohort study, 2017-2018.

OBJECTIVES: In Australia, while prostate-specific antigen (PSA) testing rates vary by broad area-based categories of remoteness and socio-economic status, little is known about the extent of variation within them. This study aims to describe the small-area variation in PSA testing across Australia. STUDY DESIGN: This was a retrospective population-based cohort study. METHODS: We received data for PSA testing from the Australian Medicare Benefits Schedule. The cohort included men (n = 925,079) aged 50-79 years who had at least one PSA test during 2017-2018. A probability-based concordance was applied across multiple iterations (n = 50) to map each postcode to small areas (Statistical Areas 2; n = 2,129). For each iteration, a Bayesian spatial Leroux model was used to generate smoothed indirectly standardized incidence ratios across each small area, with estimates combined using model averaging. RESULTS: About a quarter (26%) of the male population aged 50-79 years had a PSA test during 2017-2018. Testing rates among small areas varied 20-fold. Rates were higher (exceedance probability>0.8) compared with the Australian average in the majority of small areas in southern Victoria and South Australia, south-west Queensland, and some coastal regions of Western Australia but lower (exceedance probability<0.2) in Tasmania and Northern Territory. CONCLUSIONS: The substantial geographical variation in PSA testing rates across small areas of Australia may be influenced by differences in access to and guidance provided by clinicians and attitudes and preferences of men. Greater understanding of PSA testing patterns by subregions and how these patterns relate to health outcomes could inform evidence-based approaches to identifying and managing prostate cancer risk.

Evaluation of food security status, psychological well-being, and stress on BMI and diet-related behaviors among a sample of college students.

OBJECTIVES: The purpose of this study was to evaluate food insecurity on body mass index (BMI) and diet-related behaviors among college students and whether psychological well-being (PWB) and stress levels mediate this relationship. STUDY DESIGN: This was a cross-sectional study. METHODS: Data from 1439 students from the American College Health Association National College Health Assessment III (Fall 2020) were used. Food security status was evaluated by the USDA Six-Item Short Form. PWB was measured using the Diener Flourishing Scale. Diet-related behaviors included the average servings of fruits, vegetables, and sugar-sweetened beverages consumed per day. Stress was measured by self-reported levels. Regression model analysis evaluated the influence of food security status, PWB, and stress levels on BMI. PWB and stress were also tested as mediators in the relationship between food insecurity and BMI. RESULTS: Among our sample of college students, 44.54% (n = 641) were food insecure, and 55.46% (n = 798) were food secure. Multiple regression analysis showed that higher food insecurity, older age, full-time enrollment status, and fifth-year student status were positively associated with a higher BMI score (P < 0.05). Results from mediation models revealed that PWB, but not stress, mediated the relationship between food security and BMI among Black/African American students. Regarding diet-related behaviors, high stress levels mediated the relationship between food insecurity and sugar-sweetened beverage intake among students. CONCLUSIONS: Food insecurity appears to influence BMI in college students. This relationship seems to be mediated by disrupted PWB and a higher intake of sugar-sweetened beverages due to stress.

Anxiety, attitudes, and education about fertility among medical students in the United States.

BACKGROUND: As delayed family building is common among physicians, the goal of this study was to evaluate childbearing plans, anxiety related to future fertility, and interest in fertility education among medical students. METHODS: Using convenience and snowball sampling methods, an electronic REDCap survey was distributed via social media and group messaging applications to medical students enrolled in medical schools across the United States. Answers were collected, and analysis of the descriptive statistics was performed. RESULTS: The survey was completed by 175 participants, 72% of which were female (assigned at birth). The mean (± SD) age of participants was 24.9 ± 1.9 years. Of all participants, 78.3% desire to have children and 65.1% of these individuals plan to delay childbearing. On average, the planned age of first pregnancy is 31.0 ± 2.3 years. "Lack of time" was the greatest influence on decision regarding timing of childbearing. Of all respondents, 58.9% reported at least some anxiety related to future fertility. When females and males were compared, significantly more females (73.8%) versus males (20.4%) reported worrying about future fertility (p < 0.001). Participants reported that greater knowledge about infertility and potential treatments would help ease fertility related anxiety, and 66.9% of respondents showed interest in learning about how things such as age and lifestyle can impact fertility, preferably through medical curricula, videos, and podcasts. CONCLUSION: A majority of the medical students in this cohort intend to have children and most plan to delay childbearing. A large percentage of female medical students reported anxiety related to future fertility, but many students showed interest in receiving fertility education. This study highlights an opportunity for medical school educators to incorporate targeted fertility education into their curriculum with the intention of decreasing anxiety and improving future reproductive success.

Prevalence of pest nematodes associated with soybean (Glycine max) in Wisconsin from 1998 to 2021.

The prevalence of Heterodera glycines and other cyst and vermiform genera was determined from 8,009 soil samples over two decades. Prevalence of cyst nematodes for farms increased from 16% in 1998 to 1999, reaching a peak of 40%, with marked differences among Wisconsin's nine agricultural districts in how much the odds of a positive test increased. Estimates at the sample scale also increased over time but peaked at 29%. Assay of all nematodes beginning in 2012 showed Pratylenchus, Helicotylenchus, and Xiphinema to be more prevalent in Wisconsin soybean fields than cyst nematodes. Prevalence estimates for Pratylenchus and Helicotylenchus for soybean and rotation crops ranged from 76 to 89% and 58 to 83%, respectively. Species identification of Pratylenchus from a subset of the samples revealed six species. The majority of cyst-positive samples were infested with Pratylenchus, and count data showed that the number of cyst eggs and juveniles per 100 cm3 soil was 60% lower in samples positive for Pratylenchus. The influence was reciprocal, as Pratylenchus population densities were 41% lower in samples positive for cyst nematodes, suggesting a competitive interaction. The Wisconsin soybean nematode testing program provides a useful model for estimating nematode prevalence using citizen-based surveys.

FIGHT-101, a first-in-human study of potent and selective FGFR 1-3 inhibitor pemigatinib in pan-cancer patients with FGF/FGFR alterations and advanced malignancies.

BACKGROUND: The phase I/II FIGHT-101 study (NCT02393248) evaluated safety, pharmacokinetics, pharmacodynamics, and preliminary efficacy of pemigatinib, a potent and selective fibroblast growth factor receptor (FGFR) 1-3 inhibitor, as monotherapy or in combination therapy, for refractory advanced malignancies, with and without fibroblast growth factor (FGF) and receptor (FGFR) gene alterations. PATIENTS AND METHODS: Eligible, molecularly unselected patients with advanced malignancies were included in part 1 (dose escalation; 3 + 3 design) to determine the maximum tolerated dose. Part 2 (dose expansion) evaluated the recommended phase II dose in tumors with or where FGF/FGFR activity is relevant. RESULTS: Patients (N = 128) received pemigatinib 1-20 mg once daily intermittently (2 weeks on/1 week off; n = 70) or continuously (n = 58). No dose-limiting toxicities were reported. Doses ≥4 mg were pharmacologically active (maximum tolerated dose not reached; recommended phase II dose 13.5 mg once daily). The most common treatment-emergent adverse event (TEAE) was hyperphosphatemia (75.0%; grade ≥3, 2.3%); the most common grade ≥3 TEAE was fatigue (10.2%). Dose interruption, dose reduction, and TEAE-related treatment discontinuation occurred in 66 (51.6%), 14 (10.9%), and 13 (10.2%) patients, respectively. Overall, 12 partial responses were achieved, most commonly in cholangiocarcinoma (n = 5) as well as in a broad spectrum of tumors including head and neck, pancreatic, gallbladder, uterine, urothelial carcinoma, recurrent pilocytic astrocytoma, and non-small-cell lung cancer (each n = 1); median duration of response was 7.3 months [95% confidence interval (CI) 3.3-14.5 months]. Overall response rate was highest for patients with FGFR fusions/rearrangements [n = 5; 25.0% (95% CI 8.7% to 49.1%)], followed by those with FGFR mutations [n = 3; 23.1% (95% CI 5.0% to 53.8%)]. CONCLUSIONS: Pemigatinib was associated with a manageable safety profile and pharmacodynamic and clinical activity, with responses seen across tumors and driven by FGFR fusions/rearrangements and mutations. These results prompted a registrational study in cholangiocarcinoma and phase II/III trials in multiple tumor types demonstrating the benefit of precision therapy, even in early phase trials.

Genetic variation within the human papillomavirus type 16 genome is associated with oropharyngeal cancer prognosis.

PURPOSE: A significant barrier to adoption of de-escalated treatment protocols for human papillomavirus-driven oropharyngeal cancer (HPV-OPC) is that few predictors of poor prognosis exist. We conducted the first large whole-genome sequencing (WGS) study to characterize the genetic variation of the HPV type 16 (HPV16) genome and to evaluate its association with HPV-OPC patient survival. PATIENTS AND METHODS: A total of 460 OPC tumor specimens from two large United States medical centers (1980-2017) underwent HPV16 whole-genome sequencing. Site-specific variable positions [single nucleotide polymorphisms (SNPs)] across the HPV16 genome were identified. Cox proportional hazards model estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for overall survival by HPV16 SNPs. Harrell C-index and time-dependent positive predictive value (PPV) curves and areas under the PPV curves were used to evaluate the predictive accuracy of HPV16 SNPs for overall survival. RESULTS: A total of 384 OPC tumor specimens (83.48%) passed quality control filters with sufficient depth and coverage of HPV16 genome sequencing to be analyzed. Some 284 HPV16 SNPs with a minor allele frequency ≥1% were identified. Eight HPV16 SNPs were significantly associated with worse survival after false discovery rate correction (individual prevalence: 1.0%-5.5%; combined prevalence: 15.10%); E1 gene position 1053 [HR for overall survival (HRos): 3.75, 95% CI 1.77-7.95; Pfdr = 0.0099]; L2 gene positions 4410 (HRos: 5.32, 95% CI 1.91-14.81; Pfdr = 0.0120), 4539 (HRos: 6.54, 95% CI 2.03-21.08; Pfdr = 0.0117); 5050 (HRos: 6.53, 95% CI 2.34-18.24; Pfdr = 0.0030), and 5254 (HRos: 7.76, 95% CI 2.41-24.98; Pfdr = 0.0030); and L1 gene positions 5962 (HRos: 4.40, 95% CI 1.88-10.31; Pfdr = 0.0110) and 6025 (HRos: 5.71, 95% CI 2.43-13.41; Pfdr = 0.0008) and position 7173 within the upstream regulatory region (HRos: 9.90, 95% CI 3.05-32.12; Pfdr = 0.0007). Median survival time for patients with ≥1 high-risk HPV16 SNPs was 3.96 years compared with 18.67 years for patients without a high-risk SNP; log-rank test P < 0.001. HPV16 SNPs significantly improved the predictive accuracy for overall survival above traditional factors (age, smoking, stage, treatment); increase in C-index was 0.069 (95% CI 0.019-0.119, P < 0.001); increase in area under the PPV curve for predicting 5-year survival was 0.068 (95% CI 0.015-0.111, P = 0.008). CONCLUSIONS: HPV16 genetic variation is associated with HPV-OPC prognosis and can improve prognostic accuracy.

First Leptophobic Dark Matter Search from the Coherent-CAPTAIN-Mills Liquid Argon Detector.

We report the first results of a search for leptophobic dark matter (DM) from the Coherent-CAPTAIN-Mills (CCM) liquid argon (LAr) detector. An engineering run with 120 photomultiplier tubes (PMTs) and 17.9×10^{20} protons on target (POT) was performed in fall 2019 to study the characteristics of the CCM detector. The operation of this 10-ton detector was strictly light based with a threshold of 50 keV and used coherent elastic scattering off argon nuclei to detect DM. Despite only 1.5 months of accumulated luminosity, contaminated LAr, and nonoptimized shielding, CCM's first engineering run has already achieved sensitivity to previously unexplored parameter space of light dark matter models with a baryonic vector portal. With an expected background of 115 005 events, we observe 115 005+16.5 events which is compatible with background expectations. For a benchmark mediator-to-DM mass ratio of m_{V_{B}}/m_{χ}=2.1, DM masses within the range 9 MeV≲m_{χ}≲50 MeV are excluded at 90% C. L. in the leptophobic model after applying the Feldman-Cousins test statistic. CCM's upgraded run with 200 PMTs, filtered LAr, improved shielding, and 10 times more POT will be able to exclude the remaining thermal relic density parameter space of this model, as well as probe new parameter space of other leptophobic DM models.

Adherence to Daily Oral TDF/FTC for PrEP in Community Health Center Populations: The Sustainable Health Center Implementation PrEP Pilot (SHIPP) Study.

The prevention effectiveness of oral preexposure prophylaxis (PrEP) is highly dependent on medication adherence but no validated longer term PrEP adherence measures are readily available for use by primary care clinicians caring for diverse populations. We compared two self-report measures (number of doses missed in past 7 days and day-by-day past week pill taking) to results of tenofovir concentrations in dried blood spot (DBS) samples at quarterly visits over the first 12 months of PrEP use. 1420 men and women in five US community health centers enrolled in a medication adherence substudy. For 3, 6, 9 and 12 months, the respective percentages of persons with self-report vs DBS levels consistent having taken all 7 doses in the week prior were 71% (51%), 70% (47%), 71% (46%) and 69% (44%). Conversely, the percentage of participants reporting taking 0-1 doses in the week prior by self-report vs DBS drug levels at 3, 6, 9 and 12 months consistent with this level of nonadherence of 6% (9%), 5% (10%), 8% (9%), and 9% (15%). The estimated risk of low adherence (estimated 0-1 doses in the week prior) was higher for participants of Black (RR 1.60, CI 1.09-2.34) or "Other" race (RR 1.62, CI 0.99-2.65) compared with participants of White race; being a transgender female (RR 2.31, CI 1.33-4.02) compared to men who have sex with men; or enrollment at a study site with less experience in the provision of PrEP. The estimated risk of low adherence by DBS was lower for participants with a higher number of sex partners in the past 3 months and those having a bachelor's degree or higher. More work is needed to provide clinicians with measures to assess medication adherence in diverse US populations being prescribed PrEP to support its effective use in reducing HIV acquisition in individuals and at the community level.

Profile of reticulated platelets in the early, subacute and late phases after transient ischemic attack or ischemic stroke.

Information regarding the profile of reticulated platelets (RP) in ischemic cerebrovascular disease (CVD) patients is limited. Data from two prospective, observational, case-control studies were combined to compare the %RP using whole blood flow cytometry in patients ≤ 4 weeks of TIA/stroke onset (baseline, N = 210), and 14 ±7 days (14d, N = 182) and ≥ 90 days (90d, N = 145) after starting or changing antiplatelet therapy with healthy controls (N = 34). There were no differences in median %RP between the overall CVD patient population at baseline or 14d vs. controls (P ≥ 0.2). However, the median %RP was significantly higher in CVD patients overall at 90d (P = .036), and in the subgroup of patients with "lacunar" TIA/ischemic stroke at baseline (P = .04) and at 90d (P = .01), but not at 14d (P = .06) vs. controls. There were no significant differences in the median %RP between other TIA/stroke subgroups and controls (P ≥ 0.05). Elevated circulating reticulated platelets, as a marker of increased platelet production/turnover, may occur following an ischemic event in a well-phenotyped TIA/ischemic stroke population overall, but may precede symptom onset at least in the subgroup with small vessel occlusion. These data improve our understanding of the profile of reticulated platelets in CVD patients.

Managing organic dairy herd health: Current roles and possible future roles for veterinarians with organic dairy clientele.

This study aimed to understand the veterinary-client relationship and perspectives in organic dairy production systems. Twenty-three organic dairy producers and 12 veterinarians were interviewed using semi-structured, one-on-one interviews. Consultation with local veterinarians was typically infrequent, as there was greater reliance on other producers and organic industry professionals for advice on dairy herd health management, perhaps due to a shared focus on organic farming principles. Organic producers generally consulted local veterinarians most frequently to develop vaccine protocols, address animal health emergencies, and gain reproductive services. Common reasons organic producers cited for not regularly consulting a local veterinarian included the cost of veterinary services and a perception that local veterinarians have limited experience with organic systems and products. Some producers also expressed the idea that infrequent veterinarian usage is indicative of a healthy herd. Meanwhile, local veterinarians reported that organic dairy producers often delayed consulting them about individual cases until animal health problems were severe. Local veterinarians also identified challenges in servicing organic herds, such as the lack of standardized regulations between different organic certifiers and limited safety and efficacy data for many herd health products used by organic producers. In addition, their formal training generally did not include organic herd health strategies. Organic dairy clients were typically a small fraction of the overall workload for local veterinarians, which precluded their ability to accumulate experience. In contrast, a handful of specialized veterinarians in the organic milk processing industry work more frequently with organic producers and have published most of the available resource materials on organic dairy herd health. Veterinary-client partnerships could be improved through more open communication and discussion of the challenges identified in this study and through participatory research and outreach engagement that includes local veterinarians, organic certifiers, organic industry veterinarians, and producers.

Combining bio-telemetry and underwater imagery to elucidate the reproductive behaviour of a large, long-lived Australian freshwater teleost.

Murray cod Maccullochella peelii (Mitchell) have a key ecological role in ensuring the health of Australia's largest inland waterway, but many aspects surrounding its reproductive strategies in the wild are unknown. From 2015 to 2019 within the Northern Murray-Darling Basin, Australia, we used a combination of bio-telemetry and underwater imagery to quantify the behaviour of Murray cod across their breeding cycle in a natural riverine environment. In most years, breeding behaviour including nest site selection was observed from early-August and spawning from late-August through to late-October, which is considerably earlier than previously reported. There was a positive correlation between the onset of breeding behaviour and week-of-year, and spawning was correlated with moon-phase. Whilst some nesting sites were amongst woody debris and in hollow logs, the majority were located in shallow water on hard substrate underneath undercuts along the riverbank edge. Nests were frequently established in isolated and disconnected pools with little or no measurable flow, suggesting that river hydraulics is not a key component driving spawning of Murray cod across at least some areas of its range. Larvae were observed actively swimming and controlling their position within and near nests and used a scatter tactic when dispersing. We also established that disturbing nesting Murray cod had a negative impact on egg and larval survival. We suggest a review of current regulations to safeguard the long-term conservation of the species across all sections of its range.

High frequency UV-Vis sensors estimate error in riverine dissolved organic carbon load estimates from grab sampling.

High frequency ultraviolet - visible (UV-VIS) sensors offer a way of improving dissolved organic carbon (DOC) load estimates in rivers as they can be calibrated to DOC concentration. This is an improvement on periodic grab sampling, or the use of pumped sampling systems which store samples in-field before collection. We hypothesised that the move to high frequency measurements would increase the load estimate based on grab sampling due to systemic under-sampling of high flows. To test our hypotheses, we calibrated two sensors in contrasting catchments (Exe and Bow Brook, UK) against weekly grab sampled DOC measurements and then created an hourly time series of DOC for the two sites. Taking this measurement as a 'true' value of DOC load, we simulated 1,000 grab sampling campaigns at weekly, fortnightly and monthly frequency to understand the likely distribution of load and error estimates. We also performed an analysis of daily grab samples collected using a pumped storage sampling system with weekly collection. Our results show that: a) grab sampling systemically underestimates DOC loads and gives positively skewed distributions of results, b) this under-estimation and positive skew decreases with increasing sampling frequency, c) commonly used estimates of error in the load value are also systemically lowered by the oversampling of low, stable flows due to their dependence on the variance in the flow-weighted mean concentration, and d) that pumped storage systems may lead to under-estimation of DOC and over estimation of specific ultra-violet absorbance (SUVA), a proxy for aromaticity, due to biodegradation during storage.

Phylogenetic Analyses of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) B.1.1.7 Lineage Suggest a Single Origin Followed by Multiple Exportation Events Versus Convergent Evolution.

The emergence of new variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) herald a new phase of the pandemic. This study used state-of-the-art phylodynamic methods to ascertain that the rapid rise of B.1.1.7 "Variant of Concern" most likely occurred by global dispersal rather than convergent evolution from multiple sources.