Mainstreaming of genomic medicine in gastroenterology, present and future: a nationwide survey of UK gastroenterology trainees

Objective: Genomics and personalised medicine are increasingly relevant for patients with gastroenterological conditions. We aim to capture the current state of genomics training in gastroenterology to review current understanding, clinical experience and long-term educational needs of UK trainees. // Design and setting: A web-based nationwide survey of all UK gastroenterology specialty trainees was conducted in 2017. // Results: 100 trainees (14% of UK gastroenterology trainees) completed this survey. Only 9% and 16% of respondents believe that their local training programme adequately prepares them for the future clinical practice using genomic medicine and personalised medicine, respectively. Barriers identified include the need for greater trainee education (95%), inadequate clinical guidance to base interventions on the results of genomic testing (53%), concerns over misinterpretation by patients (43%) and overuse/misuse of testing by clinicians (34%). Survey respondents felt prepared to perform HFE genotyping (98%), assess TPMT status (97%) and interpret HLA subtyping for suspected coeliac disease (85%). However, only a minority felt prepared to perform the following investigations: polyposis screening (34%), hereditary pancreatitis screening (30%), testing for Lynch yndrome (33%) and KRAS testing for colorectal cancer (20%). Most respondents would support holding dedicated training days on genomic medicine (83%), formal training provisions for the mainstreaming of genomic testing (64%), an update to the UK gastroenterology specialty training curriculum and examinations (57%) and better-defined referral pathways for local genomic services (91%). // Conclusion: Most gastroenterology trainees in this survey feel ill equipped to practise genomic and personalised medicine as consultants. We propose specific revisions to the UK gastroenterology specialty curriculum that addresses trainees needs

How to … define clinical education research terminology: A glossary

Clinical education research (ClinEdR) utilises diverse terminology, which can lead to confusion. A common language is essential for enhancing impact. An expert panel drawn from various workstreams within the National Institute for Health and Care Research (NIHR) Incubator for Clinical Education Research was tasked with reviewing an initial list of terms for the development of a glossary of terms in the field of ClinEdR. The glossary was populated with terms, definitions and foundational papers by the authors and peer-reviewed for accuracy. The glossary of terms developed for ClinEdR should enable researchers to use a common language, promoting consistency and improving communication. We anticipate this will be useful for ClinEdR students and early career researchers. The glossary could be integrated into educational research methods courses in ClinEdR, and through critical and reflective use, enhance the quality and subsequent impact of ClinEdR

Reduced functional measure of cardiovascular reserve predicts admission to critical care unit following kidney transplantation

Background: There is currently no effective preoperative assessment for patients undergoing kidney transplantation that is able to identify those at high perioperative risk requiring admission to critical care unit (CCU). We sought to determine if functional measures of cardiovascular reserve, in particular the anaerobic threshold (VO2AT) could identify these patients. Methods: Adult patients were assessed within 4 weeks prior to kidney transplantation in a University hospital with a 37-bed CCU, between April 2010 and June 2012. Cardiopulmonary exercise testing (CPET), echocardiography and arterial applanation tonometry were performed. Results: There were 70 participants (age 41.7614.5 years, 60% male, 91.4% living donor kidney recipients, 23.4% were desensitized). 14 patients (20%) required escalation of care from the ward to CCU following transplantation. Reduced anaerobic threshold (VO2AT) was the most significant predictor, independently (OR = 0.43; 95% CI 0.27–0.68; p,0.001) and in the multivariate logistic regression analysis (adjusted OR = 0.26; 95% CI 0.12–0.59; p = 0.001). The area under the receiveroperating- characteristic curve was 0.93, based on a risk prediction model that incorporated VO2AT, body mass index and desensitization status. Neither echocardiographic nor measures of aortic compliance were significantly associated with CCU admission. Conclusions: To our knowledge, this is the first prospective observational study to demonstrate the usefulness of CPET as a preoperative risk stratification tool for patients undergoing kidney transplantation. The study suggests that VO2AT has the potential to predict perioperative morbidity in kidney transplant recipients

A gene-based SNP resource and linkage map for the copepod Tigriopus californicus

<p>Abstract</p> <p>Background</p> <p>As yet, few genomic resources have been developed in crustaceans. This lack is particularly evident in Copepoda, given the extraordinary numerical abundance, and taxonomic and ecological diversity of this group. <it>Tigriopus californicus </it>is ideally suited to serve as a genetic model copepod and has been the subject of extensive work in environmental stress and reproductive isolation. Accordingly, we set out to develop a broadly-useful panel of genetic markers and to construct a linkage map dense enough for quantitative trait locus detection in an interval mapping framework for <it>T. californicus--</it>a first for copepods.</p> <p>Results</p> <p>One hundred and ninety Single Nucleotide Polymorphisms (SNPs) were used to genotype our mapping population of 250 F₂larvae. We were able to construct a linkage map with an average intermarker distance of 1.8 cM, and a maximum intermarker distance of 10.3 cM. All markers were assembled into linkage groups, and the 12 linkage groups corresponded to the 12 known chromosomes of <it>T. californicus</it>. We estimate a total genome size of 401.0 cM, and a total coverage of 73.7%. Seventy five percent of the mapped markers were detected in 9 additional populations of <it>T. californicus</it>. Of available model arthropod genomes, we were able to show more colocalized pairs of homologues between <it>T. californicus </it>and the honeybee <it>Apis mellifera</it>, than expected by chance, suggesting preserved macrosynteny between Hymenoptera and Copepoda.</p> <p>Conclusions</p> <p>Our study provides an abundance of linked markers spanning all chromosomes. Many of these markers are also found in multiple populations of <it>T. californicus</it>, and in two other species in the genus. The genomic resource we have developed will enable mapping throughout the geographical range of this species and in closely related species. This linkage map will facilitate genome sequencing, mapping and assembly in an ecologically and taxonomically interesting group for which genomic resources are currently under development.</p

Antibody responses induced by SHIV infection are more focused than those induced by soluble native HIV-1 envelope trimers in non-human primates

The development of an effective human immunodeficiency virus (HIV-1) vaccine is a high global health priority. Soluble native-like HIV-1 envelope glycoprotein trimers (Env), including those based on the SOSIP design, have shown promise as vaccine candidates by inducing neutralizing antibody responses against the autologous virus in animal models. However, to overcome HIV-1’s extreme diversity a vaccine needs to induce broadly neutralizing antibodies (bNAbs). Such bNAbs can protect non-human primates (NHPs) and humans from infection. The prototypic BG505 SOSIP.664 immunogen is based on the BG505 env sequence isolated from an HIV-1-infected infant from Kenya who developed a bNAb response. Studying bNAb development during natural HIV-1 infection can inform vaccine design, however, it is unclear to what extent vaccine-induced antibody responses to Env are comparable to those induced by natural infection. Here, we compared Env antibody responses in BG505 SOSIP-immunized NHPs with those in BG505 SHIV-infected NHPs, by analyzing monoclonal antibodies (mAbs). We observed three major differences between BG505 SOSIP immunization and BG505 SHIV infection. First, SHIV infection resulted in more clonal expansion and less antibody diversity compared to SOSIP immunization, likely because of higher and/or prolonged antigenic stimulation and increased antigen diversity during infection. Second, while we retrieved comparatively fewer neutralizing mAbs (NAbs) from SOSIP-immunized animals, these NAbs targeted more diverse epitopes compared to NAbs from SHIV-infected animals. However, none of the NAbs, either elicited by vaccination or infection, showed any breadth. Finally, SOSIP immunization elicited antibodies against the base of the trimer, while infection did not, consistent with the base being placed onto the virus membrane in the latter setting. Together these data provide new insights into the antibody response against BG505 Env during infection and immunization and limitations that need to be overcome to induce better responses after vaccination

A review of bronchiolitis obliterans syndrome and therapeutic strategies

Lung transplantation is an important treatment option for patients with advanced lung disease. Survival rates for lung transplant recipients have improved; however, the major obstacle limiting better survival is bronchiolitis obliterans syndrome (BOS). In the last decade, survival after lung retransplantation has improved for transplant recipients with BOS. This manuscript reviews BOS along with the current therapeutic strategies, including recent outcomes for lung retransplantation

Adaptation of a Couple-Based HIV Intervention for Methamphetamine-Involved African American Men who have Sex with Men

In the U.S., incidence of HIV infection among men who have sex with men (MSM) has steadily increased since the 1990s. This points to a need for innovation to address both emerging trends as well as longer-standing disparities in HIV risk and transmission among MSM, such as the elevated rates of HIV/STIs among African American MSM and methamphetamine users. While couple-based sexual risk reduction interventions are a promising avenue to reduce HIV/STI transmission, prior research has been almost exclusively with heterosexual couples. We sought to adapt an existing, evidence-based intervention—originally developed and tested with heterosexual couples—for a new target population consisting of African American MSM in a longer-term same-sex relationship where at least one partner uses methamphetamine. The adaptation process primarily drew from data obtained from a series of focus groups with 8 couples from the target population. Attention is given to the methods used to overcome challenges faced in this adaptation process: limited time, a lead investigator who is phenotypically different from the target population, a dearth of descriptive information on the experiences and worldviews among the target population, and a concomitant lack of topical experts. We also describe a visualization tool used to ensure that the adaptation process promotes and maintains adherence to the theory that guides the intervention and behavior change. The process culminated with an intervention adapted for the new target population as well as preliminary indications that a couple-based sexual-risk reduction intervention for African American, methamphetamine-involved male couples is feasible and attractive

Postural effects of symmetrical and asymmetrical loads on the spines of schoolchildren

The school backpack constitutes a daily load for schoolchildren: we set out to analyse the postural effects of this load, considering trunk rotation, shoulder asymmetry, thoracic kyphosis, lumbar lordosis, and sagittal and frontal decompensation from the plumbline. A group of 43 subjects (mean age = 12.5 ± 0.5 years) were considered: average backpack loads and average time spent getting to/from home/school (7 min) had been determined in a previous study conducted on this population. Children were evaluated by means of an optoelectronic device in different conditions corresponding to their usual everyday school backpack activities: without load; bearing 12 (week maximum) and 8 (week average) kg symmetrical loads; bearing an 8 kg asymmetrical load; after fatigue due to backpack carrying (a 7-minute treadmill walking session bearing an 8 kg symmetrical load). Both types of load induce changes in posture: the symmetrical one in the sagittal plane, without statistical significant differences between 8 and 12 kg, and the asymmetrical one in all anatomical planes. Usual fatigue accentuates sagittal effects, but recovery of all parameters (except lumbar lordosis) follows removal of the load. The backpack load effect on schoolchildren posture should be more carefully evaluated in the future, even if we must bear in mind that laws protect workers to carry heavy loads but not children, and results in the literature support the hypothesis that back pain in youngsters is correlated with back pain in adulthoo

Tipping Point for Expansion of Layered Aluminosilicates in Weakly Polar Solvents: Supercritical CO2

Layered aluminosilicates play a dominant role in the mechanical and gas storage properties of the subsurface, are used in diverse industrial applications, and serve as model materials for understanding solvent-ion-support systems. Although expansion in the presence of H2O is well-known to be systematically correlated with the hydration free energy of the interlayer cation, particularly in environments dominated by nonpolar solvents (i.e., CO2), uptake into the interlayer is not well-understood. Using novel high-pressure capabilities, we investigated the interaction of dry supercritical CO2 with Na-, NH4-, and Cs-saturated montmorillonite, comparing results with predictions from molecular dynamics simulations. Despite the known trend in H2O and that cation solvation energies in CO2 suggest a stronger interaction with Na, both the NH4- and Cs-clays readily absorbed CO2 and expanded, while the Na-clay did not. The apparent inertness of the Na-clay was not due to kinetics, as experiments seeking a stable expanded state showed that none exists. Molecular dynamics simulations revealed a large endothermicity to CO2 intercalation in the Na-clay but little or no energy barrier for the NH4- and Cs-clays. Indeed, the combination of experiment and theory clearly demonstrate that CO2 intercalation of Na-montmorillonite clays is prohibited in the absence of H2O. Consequently, we have shown for the first time that in the presence of a low dielectric constant, gas swelling depends more on the strength of the interaction between the interlayer cation and aluminosilicate sheets and less on that with solvent. The finding suggests a distinct regime in layered aluminosilicate swelling behavior triggered by low solvent polarizability, with important implications in geomechanics, storage, and retention of volatile gases, and across industrial uses in gelling, decoloring, heterogeneous catalysis, and semipermeable reactive barriers