Evaluating the publication practices of medical students: A mixed-methods study.

PURPOSE: Engagement in research and publication helps medical students develop the skills to improve healthcare through evidence-based medicine. The qualitative evidence-base for the medical student experience of publishing is limited. This study aims to explore medical students' publication practices and understand their experiences of research and publication. METHODS: The study is based on a mixed-methods convergent design. A survey questionnaire was distributed to medical students in UK medical schools by social media and email communication. We recruited volunteer participants through the survey and interviewed a sample whilst the survey was open. We purposively selected the sample to ensure representation from research-intensive and other universities. RESULTS: Survey results indicated that 21.3% (27/127) of respondents had a publication. The most common publication type was a conference abstract. The main motivation to publish was career progression and the main barriers were lack of opportunity or support to submit an article. There was no significant association between attending a research-intensive university and submitting an article. The interviews revealed that contributing to academic advancement was also a motivation to publish. Participants expressed receiving differing levels of support from supervisors and their institutions. CONCLUSIONS: Data from the interviews suggested that the most commonly perceived barriers identified in the survey (lack of opportunity and support to conduct and publish research) may vary in prevalence between different medical schools. Further research is required to explore how different types of support offered by medical schools affect student engagement in publishing research.

Fertility in seasonal-calving pasture-based lactating dairy cows following timed artificial insemination or timed embryo transfer with fresh or frozen in vitro-produced embryos.

The objective was to compare pregnancy per service event (P/S) in lactating dairy cows following timed artificial insemination (AI) or timed embryo transfer (ET) using either fresh or frozen in vitro-produced embryos. Oocytes were collected once per week for up to 9 wk using transvaginal ovum pick-up from elite dairy donors (ET-DAIRY; n = 40; Holstein-Friesian and Jersey) and elite beef donors (ET-ELITE-BEEF; n = 21; Angus). Both ET-DAIRY and ET-ELITE-BEEF donors consisted of heifers and cows. In addition, oocytes were collected from the ovaries of beef heifers of known pedigree following slaughter at a commercial abattoir (ET-COMM-BEEF; n = 119). Following in vitro maturation and fertilization, presumptive zygotes were cultured in vitro to the blastocyst stage. Grade 1 blastocysts were either transferred fresh or frozen for on-farm thawing and direct transfer. A total of 1,106 recipient cows (all lactating, predominantly Holstein-Friesian) located on 16 herdlets were blocked based on parity, calving date, and Economic Breeding Index, and randomly assigned to receive AI (n = 243) or ET (n = 863) after estrous synchronization with a 10-d Progesterone-synch protocol. Cows assigned to ET were further randomized to receive fresh (n = 187) or frozen (n = 178) ET-ELITE-BEEF embryos, fresh (n = 169) or frozen (n = 162) ET-DAIRY embryos, or fresh (n = 80) or frozen (n = 87) ET-COMM-BEEF embryos. Pregnancy was diagnosed using transrectal ultrasound on d 32 to 35 after synchronized ovulation and confirmed on d 62 to 65, at which time fetal sex was determined. Pregnancy per service event at d 32 was not different between AI (48.8%) and ET (48.9%) and did not differ between dairy and beef embryos (50.3% vs. 48.1%, respectively). However, P/S was less on d 32 following transfer of frozen embryos (41.6%) compared with fresh embryos (56.1%). Pregnancy loss between d 32 and 62 was greater for ET (15.1%) compared with AI (4.7%), with greater losses observed for frozen beef (18.5%), fresh beef (17.3%), and frozen dairy (19.2%) compared with fresh dairy (6.0%) embryos. Serum progesterone (P4) concentration on d 7 was associated with P/S at d 32 and 62. Cows in the quartile with the least serum P4 concentrations (quartile 1) had less probability of being pregnant on d 32 (33.4%) compared with cows in the 3 upper quartiles for serum P4 (45.7%, 55.6%, and 61.2% for quartile 2, quartile 3, and quartile 4, respectively). Sex ratio (male:female) at d 62 was skewed toward more male fetuses following ET (61.1:38.9) compared with AI (43.2:56.8) and was consistent with the sex ratio among in vitro blastocysts (61.2:38.8). In conclusion, P/S was similar for AI and ET, although pregnancy loss between d 32 and 62 was greater for ET than for AI.

Dose- and time-dependent effects of interferon tau on bovine endometrial gene expression.

Failure by the developing conceptus to secrete sufficient interferon tau (IFNT), required for maternal recognition of pregnancy (MRP), at the appropriate time is related to early pregnancy loss in cattle. We aimed to test the hypothesis that there is a dose- and time-dependent relationship between IFNT and the endometrial expression of key interferon-stimulated genes (ISGs) involved in the signalling cascade leading to MRP in cattle. Candidate genes were identified first through a bioinformatic approach, where integrated transcriptomic data from two previous studies were analyzed to identify endometrial genes induced by IFNT. Next, expression of selected candidate genes was investigated in vitro in endometrial explants. Endometrial explants collected from cows (n = 8) in the late luteal phase of the estrous cycle were cultured in medium without (control) or with recombinant ovine IFNT (1, 10, 100 ng/mL) for 6 h. Simultaneously, endometrial explants were cultured in medium containing 100 ng/mL IFNT for different time periods (15 min, 30 min, 1 h, 3 h, 6 h). Gene expression was analyzed by RT-qPCR. We identified 54 endometrial genes responding to IFNT and to some degree to the conceptus, from which five ISGs (CMPK2, BPNT1, IFI35, TNFSF10 and TRIM38) were further selected for the dose- and time-dependent experiments. Classical ISGs (ISG15, OAS1, MX1 and MX2) were up-regulated (P < 0.05) in endometrium by 1 ng/mL IFNT. However, other selected ISGs (CMPK2, BPNT1, IFI35, TNFSF10 and TRIM38) were induced only by higher concentrations (10 and 100 ng/mL) of IFNT (P < 0.05). In terms of duration of exposure, IFNT at 100 ng/mL induced a significant (P < 0.05) increase in ISG15 and CMPK2 expression after 1 h incubation, while all other studied ISGs in the endometrium were upregulated when cultured for 3 or 6 h, but did not affect expression when the duration of culture was for 1 h or less. These results suggest that IFNT acts on the uterus in both a dose- and time-dependent manner in cattle and that timely exposure of the endometrium to sufficient IFNT is essential for appropriate signalling to ensure successful pregnancy establishment.

Y-Chromosome-Linked Genes Are Associated With Sex-Related Head-Neck Squamous Cell Carcinoma Survival.

OBJECTIVE: To define novel gene biomarkers for prognosis of head and neck squamous cell carcinoma (HNSCC) patients' survival. STUDY DESIGN: Retrospective study. SETTING: The Cancer Genome Atlas (TCGA) HNSCC RNA-Seq dataset. METHODS: Coexpressed gene clusters were extracted from TCGA RNA-seq data using our previously published method (EPIG). Kaplan-Meier estimator was then used for overall survival-relevant analysis, with patients partitioned into 3 groups based on gene expression levels: female, male_low, and male_high. RESULTS: Male had better overall survival than female and male with higher expression level of Y-chromosome-linked (Y-linked) genes had significantly better survival than those with lower expression levels. In addition, male with a higher expression level of Y-linked genes showed even better survival when they have a higher level of coexpressed cluster of genes related to B or T cell immune response. Other clinical conditions related to immune responses also consistently showed favorable effects on the Y-linked genes for survival estimation. Male patients with higher expression level of Y-linked genes also have significantly higher tumor/normal tissue (T/N) ratio of those genes and higher level of several immune responses related clinical measurements (eg, lymphocyte and TCR related). Male patients with lower expression level of Y-linked genes benefited from radiation-only treatment. CONCLUSIONS: The favorable role of a cluster of coexpressed Y-linked genes in HNSCC patients' survival is potentially associated with elevated level of immune responses. These Y-linked genes could serve as useful prognostic biomarkers for HNSCC patients' survival estimation and treatment.

First Direct Measurement Constraining the

The rate of the final step in the astrophysical αp process, the ^{34}Ar(α,p)^{37}K reaction, suffers from large uncertainties due to a lack of experimental data, despite having a considerable impact on the observable light curves of x-ray bursts and the composition of the ashes of hydrogen and helium burning on accreting neutron stars. We present the first direct measurement constraining the ^{34}Ar(α,p)^{37}K reaction cross section, using the Jet Experiments in Nuclear Structure and Astrophysics gas jet target. The combined cross section for the ^{34}Ar,Cl(α,p)^{37}K,Ar reaction is found to agree well with Hauser-Feshbach predictions. The ^{34}Ar(α,2p)^{36}Ar cross section, which can be exclusively attributed to the ^{34}Ar beam component, also agrees to within the typical uncertainties quoted for statistical models. This indicates the applicability of the statistical model for predicting astrophysical (α,p) reaction rates in this part of the αp process, in contrast to earlier findings from indirect reaction studies indicating orders-of-magnitude discrepancies. This removes a significant uncertainty in models of hydrogen and helium burning on accreting neutron stars.

Concordant palliative care delivery in advanced head and neck cancer.

OBJECTIVES: To describe the palliative care consultation practices in an academic head and neck surgery practice. METHODS: This is a retrospective review of a palliative care database and the health record for all palliative care consultations of patients suffering from advanced stage head and neck cancer within a 21-month period. RESULTS: Ten head and neck cancer patients received palliative care consults while on the otolaryngology service. One consultation occurred preoperatively; nine occurred postoperatively, on a median of hospital day 9. At the time of referral, seven patients were in the ICU and three were on a surgical floor. Code status de-escalation occurred in six patients and psycho-socio-spiritual suffering was supported in all consultations. Nine patients died within six months, with a median post-consultation survival of 35 days. Of these, two died in an ICU, five were discharged to hospice, one to a SNF, and one to a LTACH. CONCLUSION: Palliative care consultation in this advanced head and neck cancer cohort was commonly late, however, significant suffering was mitigated following most consults. Palliative care specialists are experts at eliciting patient values, determining acceptable tradeoffs and suffering limitations by employing a shared decision-making process that ends with a patient-centered value-congruent treatment recommendation. Oftentimes, this embraces curative-intent or palliative surgery, along with contingency plans for unacceptable value-incongruent postoperative outcomes. Enhanced awareness of the benefits of embracing concordant palliative care in advanced head and neck cancer patients may help overcome the significant barriers to involving palliative care experts earlier.

The association between iron deficiency and outcomes: a secondary analysis of the intravenous iron therapy to treat iron deficiency anaemia in patients undergoing major abdominal surgery (PREVENTT) trial.

In the intravenous iron therapy to treat iron deficiency anaemia in patients undergoing major abdominal surgery (PREVENTT) trial, the use of intravenous iron did not reduce the need for blood transfusion or reduce patient complications or length of hospital stay. As part of the trial protocol, serum was collected at randomisation and on the day of surgery. These samples were analysed in a central laboratory for markers of iron deficiency. We performed a secondary analysis to explore the potential interactions between pre-operative markers of iron deficiency and intervention status on the trial outcome measures. Absolute iron deficiency was defined as ferritin <30 µg.l-1 ; functional iron deficiency as ferritin 30-100 µg.l-1 or transferrin saturation < 20%; and the remainder as non-iron deficient. Interactions were estimated using generalised linear models that included different subgroup indicators of baseline iron status. Co-primary endpoints were blood transfusion or death and number of blood transfusions, from randomisation to 30 days postoperatively. Secondary endpoints included peri-operative change in haemoglobin, postoperative complications and length of hospital stay. Most patients had iron deficiency (369/452 [82%]) at randomisation; one-third had absolute iron deficiency (144/452 [32%]) and half had functional iron deficiency (225/452 [50%]). The change in pre-operative haemoglobin with intravenous iron compared with placebo was greatest in patients with absolute iron deficiency, mean difference 8.9 g.l-1 , 95%CI 5.3-12.5; moderate in functional iron deficiency, mean difference 2.8 g.l-1 , 95%CI -0.1 to 5.7; and with little change seen in those patients who were non-iron deficient. Subgroup analyses did not suggest that intravenous iron compared with placebo reduced the likelihood of death or blood transfusion at 30 days differentially across subgroups according to baseline ferritin (p = 0.33 for interaction), transferrin saturation (p = 0.13) or in combination (p = 0.45), or for the number of blood transfusions (p = 0.06, 0.29, and 0.39, respectively). There was no beneficial effect of the use of intravenous iron compared with placebo, regardless of the metrics to diagnose iron deficiency, on postoperative complications or length of hospital stay.

Early [18]FDG PET/CT scan predicts tumor response in head and neck squamous cell cancer patients treated with erlotinib adjusted per smoking status.

Translational Relevance: Evaluation of targeted therapies is urgently needed for the majority of patients with metastatic/recurrent head and neck squamous cell carcinoma (HNSCC) who progress after immunochemotherapy. Erlotinib, a targeted inhibitor of epidermal growth factor receptor pathway, lacks FDA approval in HNSCC due to inadequate tumor response. This study identifies two potential avenues to improve tumor response to erlotinib among patients with HNSCC. For the first time, this study shows that an increased erlotinib dose of 300 mg in smokers is well-tolerated and produces similar plasma drug concentration as the regular dose of 150 mg in non-smokers, with increased study-specific defined tumor response. The study also highlights the opportunity for improved patient selection for erlotinib treatment by demonstrating that early in-treatment [18]FDG PET/CT is a potential predictor of tumor response, with robust statistical correlations between metabolic changes on early in-treatment PET (4-7 days through treatment) and anatomic response measured by end-of-treatment CT. Purpose: Patients with advanced HNSCC failing immunochemotherapy have no standard treatment options. Accelerating the investigation of targeted drug therapies is imperative. Treatment with erlotinib produced low response rates in HNSCC. This study investigates the possibility of improved treatment response through patient smoking status-based erlotinib dose optimization, and through early in-treatment [18]FDG PET evaluation to differentiate responders from non-responders. Experimental design: In this window-of-opportunity study, patients with operable HNSCC received neoadjuvant erlotinib with dose determined by smoking status: 150 mg (E150) for non-smokers and 300 mg (E300) for active smokers. Plasma erlotinib levels were measured using mass spectrometry. Patients underwent PET/CT before treatment, between days 4-7 of treatment, and before surgery (post-treatment). Response was measured by diagnostic CT and was defined as decrease in maximum tumor diameter by ≥ 20% (responders), 10-19% (minimum-responders), and < 10% (non-responders). Results: Nineteen patients completed treatment, ten of whom were smokers. There were eleven responders, five minimum-responders, and three non-responders. Tumor response and plasma erlotinib levels were similar between the E150 and E300 patient groups. The percentage change on early PET/CT and post-treatment PET/CT compared to pre-treatment PET/CT were significantly correlated with the radiologic response on post-treatment CTs: R=0.63, p=0.0041 and R=0.71, p=0.00094, respectively. Conclusion: This pilot study suggests that early in-treatment PET/CT can predict response to erlotinib, and treatment with erlotinib dose adjusted according to smoking status is well-tolerated and may improve treatment response in HNSCC. These findings could help optimize erlotinib treatment in HNSCC and should be further investigated. Clinical Trial Registration: https://clinicaltrials.gov/ct2/show/NCT00601913, identifier NCT00601913.

Constructing evidence-based clinical intrapartum care algorithms for decision-support tools.

AIM: To describe standardised iterative methods used by a multidisciplinary group to develop evidence-based clinical intrapartum care algorithms for the management of uneventful and complicated labours. POPULATION: Singleton, term pregnancies considered to be at low risk of developing complications at admission to the birthing facility. SETTING: Health facilities in low- and middle-income countries. SEARCH STRATEGY: Literature reviews were conducted to identify standardised methods for algorithm development and examples from other fields, and evidence and guidelines for intrapartum care. Searches for different algorithm topics were last updated between January and October 2020 and included a combination of terms such as 'labour', 'intrapartum', 'algorithms' and specific topic terms, using Cochrane Library and MEDLINE/PubMED, CINAHL, National Guidelines Clearinghouse and Google. CASE SCENARIOS: Nine algorithm topics were identified for monitoring and management of uncomplicated labour and childbirth, identification and management of abnormalities of fetal heart rate, liquor, uterine contractions, labour progress, maternal pulse and blood pressure, temperature, urine and complicated third stage of labour. Each topic included between two and four case scenarios covering most common deviations, severity of related complications or critical clinical outcomes. CONCLUSIONS: Intrapartum care algorithms provide a framework for monitoring women, and identifying and managing complications during labour and childbirth. These algorithms will support implementation of WHO recommendations and facilitate the development by stakeholders of evidence-based, up to date, paper-based or digital reminders and decision-support tools. The algorithms need to be field tested and may need to be adapted to specific contexts. TWEETABLE ABSTRACT: Evidence-based intrapartum care clinical algorithms for a safe and positive childbirth experience.

The prevalence and distribution of Anaplasma phagocytophilum genotypes in Ixodes ricinus nymphs collected from farm- and woodland sites in Ireland.

Despite the economic importance of grass-based livestock production in Ireland and the fact that many veterinarians and farmers regard tickborne fever (TBF) as an increasingly important disease, especially in sheep, little is currently known about the prevalence and genetic diversity of its causative agent, Anaplasma phagocytophilum. In the present study, 1376 nymphal Ixodes ricinus ticks collected from woodland, farmland, bog and limestone pavement habitats were screened for A. phagocytophilum using TaqMan PCR. Positive samples were further analysed by conventional nested PCR targeting the 16S rRNA, msp4 and groEL loci. Overall 4.5% I. ricinus nymphs were found to be infected. The genetic heterogeneity was comparable to that reported elsewhere in Europe, with greater genetic diversity of 16S variants in ticks collected from farmland than from woodland. All isolates belonged to groEL ecotype I indicating that rodents and birds do not contribute to the epidemiology of tickborne fever in Ireland. In the 16S and groEL loci, a number of the Irish isolates matched European sequences from humans, horses and dogs. The 16S sequences that were identical to human isolates from Europe also matched Ap-ha, the most common human pathogenic strain in the USA. Three isolates also matched published sequences from horses in the msp4 locus. No isolate matched human, equine and canine sequences in all 3 loci. Our results represent the first molecular characterization of Irish A. phagocytophilum isolates.

Development of a focal lesion phantom with clinically relevant lesion characteristics for image quality evaluation of breast ultrasound scanners.

PURPOSE: Contrast-detail (C-D) and anechoic-target (A-T) detectability are measures of an ultrasound scanner's ability to image lesions of varying contrast and size from background tissue and, as such, they are important tools for grading the imaging capabilities of ultrasound scanners. The objective of this study was to develop a range of contrast- and anechoic-detail phantoms with clinically relevant lesions, of various contrast and sizes, for performance testing of breast ultrasound equipment. METHODS: Tissue mimicking materials that represent the acoustic properties of breast fibroglandular tissue were produced and moulded to construct a range of C-D and A-T phantoms. Two phantom designs were produced, containing cylindrical and spherical targets. Both phantom types were constructed with contrast targets covering the range anechoic, -1, -2, -3 and -4 dB, with lesion diameters of 1-4 mm, positioned at four clinically relevant depths (10, 25, 40 and 55 mm). An image analysis program was developed to objectively analyse the lesion images and to determine the lesion-signal-noise-ratio (LSNR). RESULTS: Both phantoms were used to evaluate the performance of a breast ultrasound scanner. The use of cylindrical phantoms led to an artificially higher image quality performance compared with the more clinically relevant spherical lesion phantom, thus indicating the importance of using the appropriate targets in ultrasound phantoms. CONCLUSION: The spherical lesion phantoms, coupled with the quantitative metric of LSNR, provides a comprehensive approach for performance and quality control testing, as well as the evaluation of advanced ultrasound imaging modes and technologies.

Exploiting Isospin Symmetry to Study the Role of Isomers in Stellar Environments.

Proton capture on the excited isomeric state of ^{26}Al strongly influences the abundance of ^{26}Mg ejected in explosive astronomical events and, as such, plays a critical role in determining the initial content of radiogenic ^{26}Al in presolar grains. This reaction also affects the temperature range for thermal equilibrium between the ground and isomeric levels. We present a novel technique, which exploits the isospin symmetry of the nuclear force, to address the long-standing challenge of determining proton-capture rates on excited nuclear levels. Such a technique has in-built tests that strongly support its veracity and, for the first time, we have experimentally constrained the strengths of resonances that dominate the astrophysical ^{26m}Al(p,γ)^{27}Si reaction. These constraints demonstrate that the rate is at least a factor ∼8 lower than previously expected, indicating an increase in the stellar production of ^{26}Mg and a possible need to reinvestigate sensitivity studies involving the thermal equilibration of ^{26}Al.