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Fish were kept for six weeks at three different initial stocking densities and water O2 concentrations (low-LD, 8.5 kg/m3 and 95–70% O2 saturation; medium-MD, 17 kg/m3 and 55–75% O2 saturation; high-HD, 25 kg/m3 and 60–45% O2 saturation), with water temperature increasing from 19 °C to 26–27 °C. The improvement in growth performance with the decrease in stocking density was related to changes in skin and intestinal mucosal microbiomes. Changes in microbiome composition were higher in skin, with an increased abundance of Alteromonas and Massilia in HD fish. However, these bacteria genera were mutually exclusive, and Alteromonas abundance was related to a reactive behavior and systemic growth regulation via the liver Gh/Igf system, while Massilia was correlated to a proactive behavior and a growth regulatory transition towards muscle rather than liver. At the intestinal level, microbial abundance showed an opposite trend for two bacteria taxa, rendering in a low abundance of Reyranella and a high abundance of Prauserella in HD fish. This trend was correlated with up-regulated host gene expression, affecting the immune response, epithelial cell turnover, and abiotic stress response. Most of the observed responses are adaptive in nature, and they would serve to infer new welfare indicators for increased stress resilience.

Scottish Vision Group has become a yearly event for vision scientists based in Scotland since its inception in 2001. Each year, the conference is hosted at a different location and organised by a different team. The 2023 SVG meeting was hosted in the city of Dundee by Abertay University. Delegates travelled from the United Kingdom, Europe and beyond. The meeting started with a roundtable panel discussion sponsored by Meta Reality Labs. The roundtable, titled The Past, Present and Future of Visual Search, was organised and presented by Árni Kristjánsson (Iceland), Ioan Smart (Abertay) and Ian Thornton (Malta). The MDPI Keynote lecture was introduced by Professor Andrew Parker (Oxford University and Otto-von-Guericke University in Magdeburg, Germany) and presented by Prof. Timothy Ledgeway (Nottingham) on sensory eye dominance and plasticity in adult binocular vision. The remaining two days of the conference hosted a wide range of talks on topics ranging from insect navigation to visual illusions, facial recognition and binocular coding. The Saturday evening saw a special event where delegates explored the sensory properties of a range of single-malt whiskies. Here, we present a selection of abstracts for the various talks and posters.

Feed conversion ratio (FCR) is an important trait to target in fish breeding programs, and the aim of the present study is to underline how the genetic improvement of FCR in gilthead sea bream (Sparus aurata) drives to changes in transcriptional and behavioural patterns. Groups of fish with high (FCR+) and low (FCR-) individual FCR were established at the juvenile stage (161–315 dph) by rearing isolated fish on a restricted ration. Fish were then grouped on the basis of their individual FCR and they grew up until behavioural monitoring and gene expression analyses were done at 420 dph. The AEFishBIT datalogger (externally attached to operculum) was used for simultaneous measurements of physical activity and ventilation rates. This allowed discrimination of FCR+ and FCR- groups according to their different behaviour and energy partitioning for growth and locomotor activity. Gene expression profiling of liver and white muscle was made using customized PCR-arrays of 44 and 29 genes, respectively. Up to 15 genes were differentially expressed in liver and muscle tissues highlighting a different metabolic scope of FCR+ and FCR- fish. Hepatic gene expression profile of FCR- fish displayed a lower lipogenic activity that was concurrent with a down-regulation of markers of mitochondrial activity and oxidative stress, as well as a reallocation of body fat depots with an enhanced flux of lipids towards skeletal muscle. Muscle gene expression profile of FCR- fish matched with stimulatory and inhibitory growth signals, and an activation of energy sensors and antioxidant defence as part of the operating mechanisms for a more efficient muscle growth. These new insights contribute to phenotype the genetically mediated differences in fish FCR thanks to the combination of transcriptomic and behavioural approaches that contribute to better understand the mechanisms involved in a reliable FCR improvement of farmed gilthead sea bream.

Patent foramen ovale closure (PFO) is an underutilized therapy, and our study explored the challenges and feasibility of PFO closure in the Indian setting.Eighty patients with Embolic Stroke of Undetermined Source (ESUS) were screened by transcranial Doppler (TCD) for PFO. Twenty-nine patients underwent successful closure.High-risk features of a long tunnel, inter-atrial septal aneurysm, and large defect were present in 31%, 28%, and 59%. Transcranial Doppler had a sensitivity and specificity of 78% and 53% (p = 0.02) to detect PFO. Anticoagulation was withdrawn in 85% of patients post closure. Two patients had residual shunts at follow-up of 19 (9,34) months.

Investigations to understand the function and control of the globin genes have led to some of the most exciting molecular discoveries and biomedical breakthroughs of the 20th and 21st centuries. Extensive characterization of the globin gene locus, accompanied by pioneering work on the utilization of viruses as human gene delivery tools in human hematopoietic stem and progenitor cells (HPSCs), has led to transformative and successful therapies via autologous hematopoietic stem-cell transplant with gene therapy (HSCT-GT). Due to the advanced understanding of the β-globin gene cluster, the first diseases considered for autologous HSCT-GT were two prevalent β-hemoglobinopathies: sickle cell disease and β-thalassemia, both affecting functional β-globin chains and leading to substantial morbidity. Both conditions are suitable for allogeneic HSCT; however, this therapy comes with serious risks and is most effective using an HLA-matched family donor (which is not available for most patients) to obtain optimal therapeutic and safe benefits. Transplants from unrelated or haplo-identical donors carry higher risks, although they are progressively improving. Conversely, HSCT-GT utilizes the patient’s own HSPCs, broadening access to more patients. Several gene therapy clinical trials have been reported to have achieved significant disease improvement, and more are underway. Based on the safety and the therapeutic success of autologous HSCT-GT, the U.S. Food and Drug Administration (FDA) in 2022 approved an HSCT-GT for β-thalassemia (Zynteglo™). This review illuminates the β-globin gene research journey, adversities faced, and achievements reached; it highlights important molecular and genetic findings of the β-globin locus, describes the predominant globin vectors, and concludes by describing promising results from clinical trials for both sickle cell disease and β-thalassemia.

Abstract Following a request from the European Commission, the EFSA Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) was asked to deliver a scientific opinion on the assessment of the application for the renewal of authorisation of naringin as a sensory additive for all animal species. The applicant provided data demonstrating that the additive currently in the market complies with the conditions of authorisation. The FEEDAP Panel confirms that the use of naringin under the current authorised conditions of use is safe for the target species, the consumers and the environment. Naringin does not cause severe irritation or corrosion to eyes, is not irritant to the skin and is not classified as a dermal sensitiser. The FEEDAP Panel cannot conclude on the possible respiratory sensitisation of the additive, due to the lack of data. There was no need for assessing the efficacy of the additive in the context of the renewal of the authorisation.

Behavioral parameters are reliable and useful operational welfare indicators that yield information on fish health and welfare status in aquaculture. However, aquatic environment is still constraining for some solutions based on underwater cameras or echo sounder transmitters. Thus, the use of bio-loggers internally or externally attached to sentinel fish emerges as a solution for fish welfare monitoring in tanks- and sea cages-rearing systems. This review is focused on the recently developed AEFishBIT, a small and light data storage tag designed to be externally attached to fish operculum for individual and simultaneous monitoring of swimming activity and ventilation rates under steady and unsteady swimming conditions for short-term periods. AEFishBIT is a tri-axial accelerometer with a frequency sampling of 50–100 Hz that is able to provide proxy measurements of physical and metabolic activities validated by video recording, exercise tests in swim tunnel respirometers, and differential operculum and body tail movements across fish species with differences in swimming capabilities. Tagging procedures based on tag piercing and surgery procedures are adapted to species anatomical head and operculum features, which allowed trained operators to quickly complete the tagging procedure with a fast post-tagging recovery of just 2.5–7 h in both salmonid (rainbow trout, Atlantic salmon) and non-salmonid (gilthead sea bream, European sea bass) farmed fish. Dual recorded data are processed by on-board algorithms, providing valuable information on adaptive behavior through the productive cycle with the changing environment and genetics. Such biosensing approach also provides valuable information on social behavior in terms of adaptive capacities or changes in daily or seasonal activity, linking respiratory rates with changes in metabolic rates and energy partitioning between growth and physical activity. At short-term, upcoming improvements in device design and accompanying software are envisaged, including energy-harvesting techniques aimed to prolong the battery life and the addition of a gyroscope for the estimation of the spatial distribution of fish movements. Altogether, the measured features of AEFishBIT will assist researchers, fish farmers and breeders to establish stricter welfare criteria, suitable feeding strategies, and to produce more robust and efficient fish in a changing environment, helping to improve fish management and aquaculture profitability.

Hematopoietic stem cell gene therapy is a promising approach for treating disorders of the hematopoietic system. Identifying combinations of cis-regulatory elements that do not impede packaging or transduction efficiency when included in lentiviral vectors has proven challenging. In this study, we deploy LV-MPRA (lentiviral vector-based, massively parallel reporter assay), an approach that simultaneously analyzes thousands of synthetic DNA fragments in parallel to identify sequence-intrinsic and lineage-specific enhancer function at near-base-pair resolution. We demonstrate the power of LV-MPRA in elucidating the boundaries of previously unknown intrinsic enhancer sequences of the human β-globin locus control region. Our approach facilitated the rapid assembly of novel therapeutic βAS3-globin lentiviral vectors harboring strong lineage-specific recombinant control elements capable of correcting a mouse model of sickle cell disease. LV-MPRA can be used to map any genomic locus for enhancer activity and facilitates the rapid development of therapeutic vectors for treating disorders of the hematopoietic system or other specific tissues and cell types.

Abstract Following a request from the European Commission, EFSA was asked to deliver a scientific opinion on the safety and efficacy of Bovaer® 10 as a zootechnical additive for ruminants for milk production and reproduction. Systemic exposure or site of contact toxicity for the active substance 3‐nitrooxypropanol (3‐NOP), for which genotoxicity has not been fully clarified, in the target species, is unlikely based on ADME data available. Consequently, the FEEDAP Panel concluded that Bovaer® 10 was safe for dairy cows at the maximum recommended level. However, as a margin of safety could not be established, the FEEDAP Panel could not conclude on the safety of the additive for other animal species/categories. The FEEDAP Panel considered that the consumer was exposed to 3‐nitrooxypropionic acid (NOPA), which is one of the 3‐NOP metabolites. NOPA was not genotoxic based on the studies provided. The FEEDAP Panel concluded that the use of Bovaer® 10 in animal nutrition under the conditions of use proposed was of no concern for consumer safety and for the environment. The FEEDAP Panel concluded that the active substance 3‐NOP may be harmful if inhaled. It is irritant (but not corrosive) to skin, irritant to the eyes but it is not a skin sensitiser. As the genotoxicity of 3‐NOP is not completely elucidated, the exposure through inhalation of the additive may represent an additional risk for the user. The Panel concluded that the additive has a potential to be efficacious in dairy cows to reduce enteric methane production under the proposed conditions of use. This conclusion was extrapolated to all other ruminants for milk production and reproduction.

Easy to use, but difficult to understand and master, technology leaves its mark in almost every field of our contemporary society. Commerce is one of the most widespread concepts in history, being the bedrock of human evolution through its various forms and practices. Combining the two will help humanity reach new heights in terms of online trading and understanding customer needs. The need for face to face interaction between the buyer and the supplier has been completely removed with the emergence of e-commerce and the development of e-commerce platforms. Influenced by both external and internal factors, to gain success, an online platform captures the attention of buyers, analyzing their behavior through data processing algorithms in order to obtain business information needed for the company’s business strategy. With Big Data and Data Mining, the profile of any consumer is projected directly into the platform, thus communicating the necessary information to predict the behavior in future platform visits.

Introduction Medical students may graduate with limited experience in managing acutely decompensating patients independently. As interns they often assume that mantle of responsibility. This first call simulation-based training provided fourth-year medical students with a guided experience in creating differential diagnoses and initiating diagnostic plans while resuscitating patients. Methods This simulation session was designed as a 3-hour session as part of a larger internship preparatory course for fourth-year medical students. The session contained three high-fidelity simulation scenarios involving a decompensating patient with a focus on developing a broad differential diagnosis and initiating treatment. The medical student leader for each patient encounter rotated with the remaining medical students actively involved in the peri-scenario debriefing process. The simulation effectiveness tool (SET-M), a published instrument to measure a learner's perception of how effective the simulation met their learning needs, was completed at the end of the session. Results Twenty students participated in the session and completed the SET-M. Ninety-five percent of students strongly agreed they were better prepared to respond to changes in a patient's condition and felt empowered to make clinical decisions. Of students, 100% strongly agreed that the debriefing was valuable in helping to improve their clinical judgment and contributed to their learning. Discussion Simulation-based training with facilitated, peri-scenario debriefing may be an effective method to develop confidence and clinical reasoning skills. This may help fourth-year medical students prepare for the impending responsibility to evaluate and initiate care for acutely decompensating patients.

Abstract The feed additive ‘dry grape extract 60‐20’ is a mixture of two extracts, one from the seed and the other from the skin of Vitis vinifera subsp. vinifera. It is intended to be used as a sensory additive (functional group: flavouring compound) in dogs. The additive ‘dry grape extract 60‐20’ is specified to contain ■■■■■ The applicant proposes a maximum use level of 100 mg ‘dry grape extract 60‐20’/kg of complete feedingstuffs for dogs without a withdrawal period. The FEEDAP Panel was aware of case reports indicating acute toxicity for some dogs consuming grapes or raisins at exposure levels relevant to the use of ‘dry grape extract 60‐20’. The FEEDAP Panel considered that rare idiosyncratic effects could be possibly responsible for the reported cases of fatality in dogs due to acute renal failure following exposure to different types of grapes. The FEEDAP Panel considered that the additive is poorly characterised. Based on the data available, the FEEDAP Panel was not able to conclude on the safety of ‘dry grape extract 60‐20’ when used as a feed additive for dogs. In the absence of studies to assess the safety for the user, the FEEDAP Panel could not conclude on the safety for the user when handling the additives. Since grape seed extract is used in food as flavouring, and its function in feed is essentially the same as that in food no further demonstration of efficacy was necessary.

Abstract Background The success of initiatives intended to increase the value of health care depends, in part, on the degree to which cost-conscious care is endorsed by current and future physicians. This study aimed to first analyze attitudes of U.S. physicians by age and then compare the attitudes of physicians and medical students. Methods A paper survey was mailed in mid-2012 to 3897 practicing physicians randomly selected from the American Medical Association Masterfile. An electronic survey was sent in early 2015 to all 5,992 students at 10 U.S. medical schools. Survey items measured attitudes toward cost-conscious care and perceived responsibility for reducing healthcare costs. Physician responses were first compared across age groups (30–40 years, 41–50 years, 51–60 years, and > 60 years) and then compared to student responses using Chi square tests and logistic regression analyses (controlling for sex). Results A total of 2,556 physicians (65%) and 3395 students (57%) responded. Physician attitudes generally did not differ by age, but differed significantly from those of students. Specifically, students were more likely than physicians to agree that cost to society should be important in treatment decisions (p

Abstract Background Maturity-onset diabetes of the young (MODY) is an early-onset, autosomal dominant form of non-insulin dependent diabetes. Genetic diagnosis of MODY can transform patient management. Earlier data on the genetic predisposition to MODY have come primarily from familial studies in populations of European origin. Methods In this study, we carried out a comprehensive genomic analysis of 289 individuals from India that included 152 clinically diagnosed MODY cases to identify variants in known MODY genes. Further, we have analyzed exome data to identify putative MODY relevant variants in genes previously not implicated in MODY. Functional validation of MODY relevant variants was also performed. Results We found MODY 3 (HNF1A; 7.2%) to be most frequently mutated followed by MODY 12 (ABCC8; 3.3%). They together account for ~ 11% of the cases. In addition to known MODY genes, we report the identification of variants in RFX6, WFS1, AKT2, NKX6–1 that may contribute to development of MODY. Functional assessment of the NKX6–1 variants showed that they are functionally impaired. Conclusions Our findings showed HNF1A and ABCC8 to be the most frequently mutated MODY genes in south India. Further we provide evidence for additional MODY relevant genes, such as NKX6–1, and these require further validation.

Introduction: Ruptured Sinus of Valsalva (RSOV) is a rare congenital heart disease. Indian data regarding trans-catheter device closure of RSOV is limited. In the current study we aim to look at the feasibility of using a Patent Ductus Arteriosus (PDA) occluder device for this purpose as it is a much economical alternative to the conventional devices. Aim: To study the immediate and intermediate term follow-up after RSOV device closure using PDA device. Materials and Methods: This retrospective analysis, from a large tertiary care hospital in South India, included 24 patients who underwent trans-catheter device closure of RSOV between December 2004 and December 2017, mostly using PDA occluders devices. Patient demographics, clinical characteristics, procedural and device related variables; immediate outcomes during hospital stay were collected from medical records. Follow-up data for residual shunt and complications were also collected. For the descriptive analysis, all continuous variables are expressed as mean values and standard deviation or median with range as appropriate, and discrete variables are presented as percentages. Results: Of the 24 patients 75% were males; the mean age was 35 years (range: 12-61 years). Twenty three PDA occluders (Lifetech, Cardi-O-Fix) and 1-vascular plug were used in total. Successful device closure was achieved in 21 patients (87.5%) and the result was sustained at 6 months follow-up (median follow-up was 8 months). There was one procedure related mortality (immediate) due to aneurysm rupture, one patient was referred for surgical closure (one week after percutaneous procedure) due to persistent shunt across the defect and another referred for surgery due to device embolization (after 24 hours of the procedure). No other procedure related complications such as significant aortic regurgitation or coronary artery occlusion occurred. Conclusion: Trans-catheter device closure of RSOV using PDA device occluder is a safe, feasible, effective and economical modality of treatment with good short-term and intermediate outcomes. In carefully selected patients this provides an attractive alternative to surgical closure, thereby avoiding the inherent morbidity of sternotomy and cardiopulmonary bypass.

Introduction There is a call to incorporate quality improvement and patient safety (QI/PS) content into undergraduate medical education, though limited literature exists on optimal teaching strategies. We designed a required, interactive workshop for first-year medical students to introduce principles of QI/PS, specifically focusing on student attitudes, knowledge, and skills. Methods We used active learning principles from existing literature and included the application of QI/PS concepts, engaging in PDSA (plan, do, study, act) cycles, conducting root cause analyses, and creating a fishbone diagram. Evaluation of student knowledge included pre/post assessments with locally designed multiple-choice items and a case scenario from the Quality Improvement Knowledge Application Tool. Additional students' self-assessments included perceived knowledge and problem-solving skills. We also evaluated student satisfaction with the workshop. Results Results on the direct assessment total score (n = 136) indicated significant growth from pretest (65%) to posttest (89%). Indirect assessments (n = 138) targeting perceived ability to define QI/PS principles, identify key components in a QI case scenario, explain the purpose of a fishbone diagram, apply a PDSA cycle, and create a fishbone diagram for a QI case scenario all significantly increased from pre- to postworkshop. The mean overall rating across the 2 years the workshop was administered (ns = 134, 137) was 75% (i.e., good to very good). Discussion First-year medical students' knowledge and perceived skills significantly increased from start to end of the workshop. The workshop was placed in an appropriate stage of the curriculum and contained relevant information for our learners.

Problem: Programs that encourage scholarly activities beyond the core curriculum and traditional biomedical research are now commonplace among US medical schools. Few studies have generated outcome data for these programs. The goal of the present study was to address this gap. Intervention: The Scholarly Concentration (SC) Program, established in 2006 at the Warren Alpert Medical School of Brown University, is a 4-year elective program that not only encourages students to pursue scholarly work that may include traditional biomedical research but also seeks to broaden students’ focus to include less traditional areas. We compared characteristics and academic performance of SC students and non-SC students for the graduating classes of 2010–2014. Context: Approximately one-third of our students opt to complete an SC during their 4-year undergraduate medical education. Because this program is additional to the regular MD curriculum, we sought to investigate whether SC students sustained the academic achievement of non-SC students while at the same time producing scholarly work as part of the program. Outcome: Over 5 years, 35% of students elected to enter the program and approximately 81% of these students completed the program. The parameters that were similar for both SC and non-SC students were age at matriculation, admission route, proportion of undergraduate science majors, and number of undergraduate science courses. Most academic indicators, including United States Medical Licensing Examinations scores, were similar for the two groups; however, SC students achieved more honors in the six core clerkships and were more likely to be inducted into the medical school's two honor societies. Residency specialties selected by graduates in the two groups were similar. SC students published an average of 1.3 peer-reviewed manuscripts per student, higher than the 0.8 manuscripts per non-SC student (p=0.013). Conclusions: An elective, interdisciplinary scholarly program with a focus beyond traditional biomedical research offers students the opportunity to expand the scope of their medical education without an untoward effect on academic performance or residency placement.

Introduction Rates of substance use disorders, including opioid misuse, continue to rise despite national initiatives. Because of this, health professional schools from Rhode Island joined together to design and implement a single-day interprofessional education workshop on substance use disorder training. Methods This workshop consists of four sessions. The first is a patient panel featuring both patients recovering from substance use disorders and their health care providers. Next is a naloxone administration training session. This is followed by a standardized patient session featuring an individual who requires nonopioid options for chronic pain treatment and in which health professional students work together to take a history, perform a physical examination, and develop a treatment plan. Finally, the last session is a complex paper-based case study focusing on a homeless individual with diverse medical problems requiring multifaceted care. Results A total of 540 students from a variety of health care professions participated in the workshop. Students were asked to evaluate each component of the workshop, as well as the workshop overall, on a 6-point Likert scale (1 = poor, 6 = outstanding). Students rated the overall workshop at 76% (4.54 out of 6), and the sessions received ratings ranging from 67% (4.01 out of 6 for the case study) to 83% (4.96 out of 6 for the patient/provider panel). Discussion This curriculum can be adapted and implemented at other medical schools to provide opportunities for future health care professionals to learn how to work effectively in interprofessional teams to manage substance use disorders.

Abstract Introduction There is a growing body of literature illustrating the negative impact of racial bias on clinical care. Despite the growing evidence, medical schools have been slow to make necessary curricular changes. Most attempts to educate on racial health disparities focus on transferring knowledge and do not foster the development of skills to understand one's own bias or address bias and racism in the clinical setting. To address this, we developed a small-group, case-based curriculum for rising third-year medical students. Methods This session was designed to be delivered in concurrently run, 1-hour small-group sessions, with each small group ideally comprising no more than 10 students and one facilitator. The curriculum was integrated into an existing 3-week clerkship preparation course for 122 students during the 2015–2016 academic year. The session materials include a facilitator's guide and three cases for discussion. Results The session was evaluated using a 6-point Likert scale (1 = poor, 6 = exceptional). Students rated this session overall a 4.28 out of 6 (N = 79). Qualitative feedback varied, with the most common theme focusing on the need for more time to discuss this topic. Discussion Though one session before starting clinical clerkships is not enough to maintain the practice of sustained critical thinking regarding bias and racism in clinical medicine, this session is a starting point for curriculum developers looking to use an evidence-based approach to racial bias in clinical care.

Large volumes of biomedical data are being produced every day. Leveraging such voluminous amount of patient data using data science approaches help to uncover hidden patterns, unknown correlations, and other insights of the disease. Integration of diverse genomic data with comprehensive electronic health records (EHRs) exhibit challenges, but essentially, they provide a feasible opportunity to better understand the underlying diseases, treatment patterns and develop an efficient and effective approach to identify biomarkers for diagnosis and improve therapy. Here, we describe a big data solution for diabetes, providing an efficient and responsive scientific discovery platform for researchers. Clinical phenotype data was collected from EHR of a tertiary care diabetes centre across 20 locations in India. It encompasses >20 million data points on 323,145 patients registered over 25 years. The biomedical data includes diverse collection of information such as well characterized clinical phenotypes, biochemical investigations, drug prescriptions, genotype mapping, micro- macrovascular complications of diabetes, pedigree charts. Additionally, more than 3 million genomic variants from high-throughput next generation sequencing (NGS) were analyzed, annotated and integrated into the respective patient phenotype data. Statistical methods such as t-test, ANOVA were used to describe the significance of clinical variables between subject groups. Time based visualization methods for showing temporal patterns in key clinical variables such fasting glucose, HbA1c, Albuminuria, etc. are provided. It provides a novel clinical database of information on 323,145 patients with type 2 diabetes (n=294,371), type 1 diabetes (n=1,945), gestational diabetes (n=645), prediabetes (n=7,363), patients with miscellaneous forms of diabetes including monogenic forms of diabetes (n=4,601) and normal glucose tolerance (n=12,579). It has about 144,926 diabetes patients (44.8% of total) with microvascular complications and 15,008 (4.6%) patients with macrovascular complications. It offers analytical tools to compute descriptive statistics of clinical variables for cohorts as well as visualizations to understand the disease progression of diabetes, uncover key event patterns such as episodes of high glucose levels, or drug treatments and their association with progression of disease over time. Thus, the database portal promotes practice of precision medicine and therefore useful to researchers, clinicians and pharmaceutical industry.

Abstract The Association of American Medical Colleges' Entrustable Professional Activity (EPA) 6 states that “the day 1 resident should be able to concisely present a summary of a clinical encounter to one or more members of the health care team (including patients and families) in order to achieve a shared understanding of the patient's current condition.” It further notes that the entrustable student should be able to “provide an accurate, concise, and well-organized oral presentation” and to “adjust the oral presentation to meet the needs of the receiver of the information.” This curriculum focuses specifically on how to adjust the oral presentation according to the needs of the specialty and provides a foundation upon which students can further refine their skills during clerkships. This curriculum is designed to teach second-year medical students the fundamentals of specialty-specific oral presentations just prior to the start of their clinical rotations. The curriculum covers the most common core clerkships at US medical schools: internal medicine, family medicine, pediatrics, surgery, obstetrics and gynecology, psychiatry, neurology, and emergency medicine. The curriculum serves as an extension of the MedEdPORTAL publication “Teaching Oral Presentation Skills to Second-Year Medical Students.” This curriculum was successfully deployed during Brown's Clinical Skills Clerkship (CSC) in 2015. Although there has been a session on specialty-specific OPs for the past 3 years, the current iteration of the curriculum has only been in use for 1 year. In 2015, 121 students completed the CSC. Students ranked the effectiveness of instruction on specialty-specific OPs by the senior medical students on a 1-6 Likert scale (1 = Poor, 6 = Outstanding). The mean of these scores was 4.72 (SD = 0.99). Qualitative comments suggested that students appreciated the opportunity to focus on what they would need to do in the specialty of their first clerkship, while simultaneously gaining a broad perspective of how oral presentation requirements would change during each core rotation. Students appreciated having the resources organized by specialty to access them easily both during the CSC and for future reference.

Investigations to understand the function and control of the globin genes have led to some of the most exciting molecular discoveries and biomedical breakthroughs of the 20th and 21st centuries. Extensive characterization of the globin gene locus, accompanied by pioneering work on the utilization of viruses as human gene delivery tools in human hematopoietic stem and progenitor cells (HPSCs), has led to transformative and successful therapies via autologous hematopoietic stem-cell transplant with gene therapy (HSCT-GT). Due to the advanced understanding of the β-globin gene cluster, the first diseases considered for autologous HSCT-GT were two prevalent β-hemoglobinopathies: sickle cell disease and β-thalassemia, both affecting functional β-globin chains and leading to substantial morbidity. Both conditions are suitable for allogeneic HSCT; however, this therapy comes with serious risks and is most effective using an HLA-matched family donor (which is not available for most patients) to obtain optimal therapeutic and safe benefits. Transplants from unrelated or haplo-identical donors carry higher risks, although they are progressively improving. Conversely, HSCT-GT utilizes the patient's own HSPCs, broadening access to more patients. Several gene therapy clinical trials have been reported to have achieved significant disease improvement, and more are underway. Based on the safety and the therapeutic success of autologous HSCT-GT, the U.S. Food and Drug Administration (FDA) in 2022 approved an HSCT-GT for β-thalassemia (Zynteglo™). This review illuminates the β-globin gene research journey, adversities faced, and achievements reached; it highlights important molecular and genetic findings of the β-globin locus, describes the predominant globin vectors, and concludes by describing promising results from clinical trials for both sickle cell disease and β-thalassemia.

Screening and brief interventions head the list of effective evidence-based interventions for the prevention and treatment of alcohol use disorders in healthcare settings. However, healthcare professionals have been reluctant to engage with this kind of activity both because of the sensitive nature of the subject and because delivery is potentially time-consuming. Digital technologies for behavioural change are becoming increasingly widespread and their low delivery costs make them highly attractive. Internet and mobile technologies have been shown to be effective for the treatment of depression, anxiety and smoking cessation in healthcare settings, and have the potential to add substantial value to the delivery of brief intervention for alcohol. Online alcohol questionnaires have been shown to elicit reliable responses on alcohol consumption and compared with conventional prevention techniques, digital alcohol interventions delivered in various settings have been found to be as effective in preventing alcohol-related harms. The last decade has seen the emergence of a range of approaches to the implementation in health care settings of referral to Internet based applications for screening and brief interventions (eSBI) for alcohol. Research in this area is in its infancy, but there is a small body of evidence providing early indications about implementation and sustainability, and a number of studies are currently underway. This paper examines some of the evidence emerging from these and other studies and assesses the implications for the future of eSBI delivery in primary care settings.

Lightness constancy refers to the ability to estimate an object's lightness (ie, surface reflectance), regardless of variations in the light being reflected from the object—for example, when the illumination changes or the object moves. Buckley et al (1994) observed that binocular cues improve lightness constancy. Here we explored how training improved lightness constancy under binocular, bi-ocular (identical images to each eye), and monocular viewing. Stimuli consisted of a diffusely illuminated Lambertian grey box, containing a single target: a faceted rectangular block that could be presented at a range of depths within the box. Stimuli were presented stereoscopically (to provide full binocular cues), monocularly, and bi-ocularly. In the experiment, participants were asked to select one of a number of blocks, presented below the box, that was of the same material as the target block. Four groups of participants received differing training regimes. Active training involved moving a block of fixed reflectance within the box along a user-defined path (by pressing keyboard buttons). Passive training was the same as active, except block movements were pre-recorded. One group received both active and passive training. No-training used a static presentation of blocks to indicate depth. We found that stereoscopic presentation produced the best lightness constancy. Training regimes delivered a performance difference for stereoscopic, monocular, and bi-ocular presentations, with passive and active training being equally effective. With some training regimes participants took longer to achieve their best performance.

Hematopoietic stem cell gene therapy is a promising approach for treating disorders of the hematopoietic system. Identifying combinations of cis-regulatory elements that do not impede packaging or transduction efficiency when included in lentiviral vectors has proven challenging. In this study, we deploy LV-MPRA (lentiviral vector-based, massively parallel reporter assay), an approach that simultaneously analyzes thousands of synthetic DNA fragments in parallel to identify sequence-intrinsic and lineage-specific enhancer function at near-base-pair resolution. We demonstrate the power of LV-MPRA in elucidating the boundaries of previously unknown intrinsic enhancer sequences of the human β-globin locus control region. Our approach facilitated the rapid assembly of novel therapeutic βAS3-globin lentiviral vectors harboring strong lineage-specific recombinant control elements capable of correcting a mouse model of sickle cell disease. LV-MPRA can be used to map any genomic locus for enhancer activity and facilitates the rapid development of therapeutic vectors for treating disorders of the hematopoietic system or other specific tissues and cell types.

In this study, free‐standing composites consisting of 90 wt% nanoenergetic mesoparticles are fabricated and their combustion characteristics are investigated. The findings reveal that the integrity of the mesoparticles remains intact during the printing process and a reduction in sintering is observed for the composite of mesoparticles compared to the physical mixture. However, the composite of mesoparticles exhibits noncontinuous and oscillating propagation behavior at a steady frequency of ≈5 Hz. This is attributed to insufficient heat feedback from the flame to the unburnt material. To address this issue, carbon fiber (C.F.) is introduced into the composite to enhance heat feedback to the reaction front by intercepting hot agglomerates near the burning surface. Incorporating C.F. leads to steady propagation of the composite. Agglomerate residence time and characteristic heat transfer time analysis near the burning surface indicate that while the composite without C.F. has agglomerate residence time on the same order of magnitude as the characteristic heat transfer time, the composite with C.F. has significantly increased overall agglomerate residence time compared to the characteristic heat transfer time. This confirms the enhanced heat feedback through C.F. inclusion. This study demonstrates the crucial role of heat feedback in the combustion behavior of energetic composites. [ABSTRACT FROM AUTHOR]

Fish were kept for six weeks at three different initial stocking densities and water O2 concentrations (low-LD, 8.5 kg/m3 and 95–70% O2 saturation; medium-MD, 17 kg/m3 and 55–75% O2 saturation; high-HD, 25 kg/m3 and 60–45% O2 saturation), with water temperature increasing from 19 °C to 26–27 °C. The improvement in growth performance with the decrease in stocking density was related to changes in skin and intestinal mucosal microbiomes. Changes in microbiome composition were higher in skin, with an increased abundance of Alteromonas and Massilia in HD fish. However, these bacteria genera were mutually exclusive, and Alteromonas abundance was related to a reactive behavior and systemic growth regulation via the liver Gh/Igf system, while Massilia was correlated to a proactive behavior and a growth regulatory transition towards muscle rather than liver. At the intestinal level, microbial abundance showed an opposite trend for two bacteria taxa, rendering in a low abundance of Reyranella and a high abundance of Prauserella in HD fish. This trend was correlated with up-regulated host gene expression, affecting the immune response, epithelial cell turnover, and abiotic stress response. Most of the observed responses are adaptive in nature, and they would serve to infer new welfare indicators for increased stress resilience. [ABSTRACT FROM AUTHOR]