Prevalence of endocrine and genetic abnormalities in boys evaluated systematically for a disorder of sex development.

STUDY QUESTION: What is the likelihood of identifying genetic or endocrine abnormalities in a group of boys with 46, XY who present to a specialist clinic with a suspected disorder of sex development (DSD)? SUMMARY ANSWER: An endocrine abnormality of the gonadal axis may be present in a quarter of cases and copy number variants (CNVs) or single gene variants may be present in about half of the cases. WHAT IS KNOWN ALREADY: Evaluation of 46, XY DSD requires a combination of endocrine and genetic tests but the prevalence of these abnormalities in a sufficiently large group of boys presenting to one specialist multidisciplinary service is unclear. STUDY, DESIGN, SIZE, DURATION: This study was a retrospective review of investigations performed on 122 boys. PARTICIPANTS/MATERIALS, SETTING, METHODS: All boys who attended the Glasgow DSD clinic, between 2010 and 2015 were included in the study. The median external masculinization score (EMS) of this group was 9 (range 1-11). Details of phenotype, endocrine and genetic investigations were obtained from case records. MAIN RESULTS AND THE ROLE OF CHANCE: An endocrine abnormality of gonadal function was present in 28 (23%) with a median EMS of 8.3 (1-10.5) whilst the median EMS of boys with normal endocrine investigations was 9 (1.5-11) (P = 0.03). Endocrine abnormalities included a disorder of gonadal development in 19 (16%), LH deficiency in 5 (4%) and a disorder of androgen synthesis in 4 (3%) boys. Of 43 cases who had array-comparative genomic hybridization (array-CGH), CNVs were reported in 13 (30%) with a median EMS of 8.5 (1.5-11). Candidate gene analysis using a limited seven-gene panel in 64 boys identified variants in 9 (14%) with a median EMS of 8 (1-9). Of the 21 boys with a genetic abnormality, 11 (52%) had normal endocrine investigations. LIMITATIONS, REASONS FOR CAUTION: A selection bias for performing array-CGH in cases with multiple congenital malformations may have led to a high yield of CNVs. It is also possible that the yield of single gene variants may have been higher than reported if the investigators had used a more extended gene panel. WIDER IMPLICATIONS OF THE FINDINGS: The lack of a clear association between the extent of under-masculinization and presence of endocrine and genetic abnormalities suggests a role for parallel endocrine and genetic investigations in cases of suspected XY DSD. STUDY FUNDING/COMPETING INTEREST(S): RN was supported by the James Paterson Bursary and the Glasgow Children's Hospital Charity Summer Scholarship. SFA, RM and EST are supported by a Scottish Executive Health Department grant 74250/1 for the Scottish Genomes Partnership. EST is also supported by MRC/EPSRC Molecular Pathology Node and Wellcome Trust ISSF funding. There are no conflicts of interest. TRIAL REGISTRATION NUMBER: None.

Neurobiological and psychological evidence of chronic stress in prostate cancer patients.

To measure the prevalence and severity of Generalised Anxiety Disorder (GAD), hypo- and hypercortisolaemia, and their association in a sample of prostate cancer (PCa) patients, 97 Australian PCa patients completed a background questionnaire and the GAD-7, and provided a sample of saliva collected 30-45 min after waking. The mean GAD7 score was 9.67 (SD = 3.09), and prevalence rates for current anxiety were higher than those reported for non-PCa males of a similar age. Mean salivary cortisol concentrations (30.78 nmol/L, SD = 13.97 nmol/L) were also higher than for age-comparative non-PCa men. There was a significant inverse correlation between GAD and cortisol (r = -. 209, p < .05), and four subgroups of GAD-cortisol patients were able to be identified, with evidence of both hyper- and hypocortisolaemia. These findings provide initial neurobiological evidence of the chronic and profound nature of stress experienced by PCa patients, and also suggest a possible measure that might be used to identify most at-risk PCa patients.

Elements and elasmobranchs: hypotheses, assumptions and limitations of elemental analysis.

Quantifying the elemental composition of elasmobranch calcified cartilage (hard parts) has the potential to answer a range of ecological and biological questions, at both the individual and population level. Few studies, however, have employed elemental analyses of elasmobranch hard parts. This paper provides an overview of the range of applications of elemental analysis in elasmobranchs, discussing the assumptions and potential limitations in cartilaginous fishes. It also reviews the available information on biotic and abiotic factors influencing patterns of elemental incorporation into hard parts of elasmobranchs and provides some comparative elemental assays and mapping in an attempt to fill knowledge gaps. Directions for future experimental research are highlighted to better understand fundamental elemental dynamics in elasmobranch hard parts.

Preoperative radiotherapy in the management of retroperitoneal liposarcoma.

BACKGROUND: Histological subtype influences both prognosis and patterns of treatment failure in retroperitoneal sarcoma. Previous studies on the efficacy of neoadjuvant radiotherapy (NRT) have incorporated multiple histological types with heterogeneous tumour biology. The survival impact of NRT specifically for patients with retroperitoneal liposarcoma is poorly defined. METHODS: Patients who underwent resection with curative intent for retroperitoneal liposarcoma and who received NRT or surgery alone were identified in the US National Cancer Data Base (2004-2013). Cox regression was used to identify co-variables associated with overall survival. NRT and surgery-alone cohorts were matched 1 : 1 by propensity scores based on the survival hazard on Cox modelling. Overall survival was compared by Kaplan-Meier estimates. RESULTS: A total of 2082 patients with retroperitoneal liposarcoma were identified; 1908 underwent surgery alone and 174 received NRT before surgical resection. Median tumour size was 22·0 cm and 34·9 per cent of tumours were high grade. In the unmatched cohort, NRT was not associated with improved overall survival (χ2 = 3·49, P = 0·062). In the propensity score-matched cohort, NRT was associated with an improvement in survival (median overall survival 129·2 versus 84·3 months; P = 0·046; hazard ratio (HR) 1·54, 95 per cent c.i. 1·01 to 2·36). This effect appeared most pronounced for tumours with adjacent organ invasion (median overall survival not reached versus 63·8 months; P = 0·044; HR 1·79, 1·01 to 3·19). CONCLUSION: NRT improved survival in patients undergoing surgery for retroperitoneal liposarcoma, particularly those with high-risk pathological features.

Expression of Bacterial Blight Resistance in Brassica Leafy Greens Under Field Conditions and Inheritance of Resistance in a Brassica juncea Source.

Brassica leafy greens are one of the most economically important vegetable commodity groups grown in the southeastern United States, and more than 28,000 metric tons of these crops are harvested in the United States annually. Collard and kale (Brassica oleracea Acephala group), mustard green (B. juncea), and turnip green (B. rapa) are the most commonly planted members of the brassica leafy greens group. In the last 10 years, numerous occurrences of bacterial blight on these leafy vegetables have been reported in several states. One of the pathogens responsible for this blight is designated Pseudomonas cannabina pv. alisalensis. Two B. rapa (G30710 and G30499) and two B. juncea (PI418956 and G30988) plant introductions (PIs) that exhibited moderate to high levels of resistance to this pathogen in greenhouse studies were tested for field resistance in comparison with eight commercial cultivar representatives of turnip green, mustard green, collard, and kale. The two B. juncea PIs and one of the B. rapa PIs (G30499) were found to have significantly less disease than all tested cultivars except 'Southern Curled Giant' mustard green (B. juncea) and 'Blue Knight' kale (B. oleracea). Inheritance of resistance studies performed with populations derived from the resistant G30988 and two susceptible PIs provided some evidence that resistance may be controlled by a single recessive gene.

Surgical time-out procedures: a single centre audit of standardised surgical communications.

OBJECTIVE: To assess deviation from a standardised structure of surgical time-out procedures in a multidisciplinary referral hospital. MATERIALS AND METHODS: An observational process audit was performed on a convenience sample of surgical cases. A fly-on-the-wall observer assessed surgical time-out procedures in real-time. Pre-induction and recovery checklists were not assessed. Observations were recorded on standardised reporting forms including a checklist and free text. Analysis was performed using a validated framework of four conceptual domains: the purpose, occasion, audience and content of the communication. Field notes were taken to allow retrospective verification of assessments. Observations were compared to a predefined standardised surgical time-out procedure structure. RESULTS: Twenty surgical time-out procedures were observed from a mixture of procedure types. Although all were performed at the specified time and place, only eight (40%) were considered to have fully achieved their purpose with potentially important sections of the communication being omitted in the others. Individuals were not ready for communication to begin in 14 (70%) and distractions occurred in 11 surgical time-out procedures (55%). In seven surgical time-out procedures (35%) superfluous information was communicated. CLINICAL SIGNIFICANCE: In a busy operating theatre environment, surgical time-out procedures may not be performed as they are intended. Communication during surgical time-out procedures should be audited to highlight opportunities for improvement.

A comparison of the effect of two types of vibration exercise on the endocrine and musculoskeletal system.

BACKGROUND: Whole body vibration (WBV) is a novel training intervention but a comparison of different methods of WBV has rarely been performed. AIM: To compare the short and medium term effects of two regimens of WBV on endocrine status, muscle function and markers of bone turnover. PATIENTS AND METHODS: Over a period of 16 weeks, 10 men with a median age of 33 yrs (range, 29,49), were randomised to stand on the Galileo platform (GP) or Juvent1000 platform (JP) 3 times/wk. The total study duration was 16 weeks with measurements performed in a 4 week period of run-in, 8 weeks of WBV and a 4 week period of washout. These measurements included an assessment of anthropometry, body composition, muscle function and biochemical markers of endocrine status and bone turnover. To assess immediate effects of WBV, measurements were also performed at 60 mins before and 5, 30 and 60 mins after WBV. To assess immediate effects of WBV, measurements were also performed at 60 mins before and 5, 30 and 60 mins after WBV. RESULTS: GP at 22 Hz was associated with an immediate increase in serum GH, rising from 0.07 µg/l (0.04,0.69) to 0.52 µg/l (0.06,2.4) (p=0.06), 0.63 µg/l (0.1,1.18) (p=0.03), 0.21 µg/l (0.07,0.65) (p=0.2) at 5 mins, 20 mins and 60 mins after WBV, respectively. An immediate effect was also observed in median serum cortisol which reduced from 316 nmol/l (247,442) before WBV to 173 nmol/l (123,245) (p=0.01),165 nmol/l (139,276) (p=0.02) and 198 nmol/l (106,294) (p=0.04) at 5 mins, 20 mins and 60 mins after WBV, respectively. Median serum CTX reduced significantly after 8 weeks of WBV training in the GP group from 0.42 ng/ml (0.29,0.90) pre-WBV to 0.29 ng/ml (0.18,0.44) at the end of WBV training (p=0.03). Over the 8 weeks, there was a reduction in median serum cortisol in the GP group from 333 nmol/l (242,445) (pre-WBV) to 270 nmol/l (115,323) (WBV) (p=0.04). None of the changes observed in the JP group reached statistical significance. Neither group showed any significant effect on muscle function, IGF-1, testosterone, leptin, CRP, creatine kinase, insulin or other markers of bone turnover. CONCLUSION: WBV can stimulate GH secretion, reduce circulating cortisol and reduce bone resorption. These effects are independent of clear changes in muscle function and depend on the type of WBV that is administered.

Diagnostic terminology in Placenta Accreta Spectrum: a scoping review.

BACKGROUND: Anaesthetic management strategies for Placenta Accreta Spectrum (PAS) remain diverse, and literature interpretation is complicated by a range of terminology. The International Federation for Gynaecology and Obstetrics (FIGO) published guidance in 2018 to improve PAS diagnosis and management by standardising definitions. We mapped the range, clarity and consistency of terminology in literature pertaining to both PAS and anaesthesia, and determined whether this changed followed FIGO guidance. METHODS: A literature search of four medical databases was performed. Papers included had PAS (or any 'synonym') in the title, and mode of anaesthesia in the title or abstract. Narrative reviews, and papers not containing original data, were excluded. Diagnostic terms, and evidence supporting their use, were described. RESULTS: Among 680 abstracts identified, 62 papers were included. Thirty distinct terms were used to describe PAS and subtypes. Terminology was clearly defined 46% of the time and used consistently within a paper 47% of the time. Nine papers (15%) provided no diagnostic evidence to support the terminology used. In 14 (23%) papers published after FIGO guidelines, 14 terms were used to describe PAS. Two papers (14%) specified the diagnostic criteria used. Six (43%) confirmed diagnoses using pathology. Four (29%) were consistent in use of terminology throughout the paper. CONCLUSIONS: Despite international consensus criteria for reporting PAS, the language pertaining to PAS and anaesthesia remains heterogeneous, inconsistent and variably defined. Reporting of PAS should adhere to FIGO criteria to allow unambiguous interpretation of work, and generation of evidence that is transferrable into clinical practice.

Defective post-thymic tolerance mechanisms during the chronic progressive stage of multiple sclerosis.

We have recently isolated a panel of T-cell clones from chronic progressive multiple sclerosis (MS) patients that are capable of functioning as antigen-presenting cells and of expressing the costimulatory molecules B7-1 and B7-2. In this report we show that these T-cell clones are resistant to inhibitory regulation, including the induction of anergy and sensitivity to tumor growth factor-beta (TGF-beta)-induced growth inhibition. The resistance to anergy induction was associated with expression of B7 costimulatory molecules. These data suggest that lack of responsiveness to peripheral inhibitory signals may account for the entry of autoimmune diseases into a chronic progressive phase.

Sustainable veterinary anaesthesia: single centre audit of oxygen and inhaled anaesthetic consumption and comparisons to a hypothetical model.

OBJECTIVES: Single centre carbon footprint audit of oxygen and inhaled anaesthetic agent consumption. STUDY DESIGN: Retrospective audit with hypothetical intervention. MATERIALS AND METHODS: Records of 100 consecutive anaesthetics were examined. Consumption of oxygen and inhaled anaesthetic agent were estimated from oxygen flowmeter and vaporiser settings. Carbon dioxide equivalents (kg CO2 e) were calculated. Records were reassessed to identify potential reductions in oxygen flow. Animals >5 kg were assigned to use circle systems set at a maintenance flow of 1 L/min following a short transitional period of higher flow. Animals <5 kg were assigned to Mapleson-A breathing systems at a flow of 1 L/min. Potential reductions in oxygen and inhaled anaesthetic agent consumption and CO2 e were calculated. RESULTS: A total of 14,370 minutes of anaesthesia were audited. Median bodyweight of the animals was 12.1 (interquartile range 5 to 25.8) kg. Median anaesthetic time was 110 (interquartile range 73.8 to 205) minutes. It was estimated 43,132 L of oxygen were used to vaporise 2605 mL of liquid sevoflurane and 1654 mL of liquid isoflurane. Potential oxygen consumption was 16,798 L, lowering sevoflurane consumption to 1123 mL and isoflurane to 589 mL. Using the suggested technique, oxygen and inhaled anaesthetic agent could have been reduced in 97% of anaesthetics with a median inhaled anaesthetic agent reduction of 59% (interquartile range 43 to 71%). Carbon footprint of the inhaled anaesthetic agent used was calculated as 1.82 metric tonnes of CO2 e. This could have been lowered to 0.67 metric tonnes (63% reduction). CLINICAL SIGNIFICANCE: Large reductions in oxygen and inhaled anaesthetic agent consumption and therefore greenhouse gas emission and financial expenditure can be made if we audit and adapt our practices.

Grow or go? Energetic constraints on shark pup dispersal from pupping areas.

Many sharks and other marine taxa use natal areas to maximize survival of young, meaning such areas are often attributed conservation value. The use of natal areas is often linked to predator avoidance or food resources. However, energetic constraints that may influence dispersal of young and their use of natal areas are poorly understood. We combined swim-tunnel respirometry, calorimetry, lipid class analysis and a bioenergetics model to investigate how energy demands influence dispersal of young in a globally distributed shark. The school shark (a.k.a. soupfin, tope), Galeorhinus galeus, is Critically Endangered due to overfishing and is one of many sharks that use protected natal areas in Australia. Energy storage in neonate pups was limited by small livers, low overall lipid content and low levels of energy storage lipids (e.g. triacylglycerols) relative to adults, with energy stores sufficient to sustain routine demands for 1.3-4 days (mean ± SD: 2.4 ± 0.8 days). High levels of growth-associated structural lipids (e.g. phospholipids) and high energetic cost of growth suggested large investment in growth during residency in natal areas. Rapid growth (~40% in length) between birth in summer and dispersal in late autumn-winter likely increased survival by reducing predation and improving foraging ability. Delaying dispersal may allow prioritization of growth and may also provide energy savings through improved swimming efficiency and cooler ambient temperatures (daily ration was predicted to fall by around a third in winter). Neonate school sharks are therefore ill-equipped for large-scale dispersal and neonates recorded in the northwest of their Australian distribution are likely born locally, not at known south-eastern pupping areas. This suggests the existence of previously unrecorded school shark pupping areas. Integrated bioenergetic approaches as applied here may help to understand dispersal from natal areas in other taxa, such as teleost fishes, elasmobranchs and invertebrates.

Mass spectrometry measurement of a therapeutic peptide for use in multiple sclerosis.

Multiple sclerosis is an autoimmune disease of the central nervous system believed to be mediated by pathogenic T lymphocytes. We have developed a next-generation therapy in which cells secrete specific therapeutic molecules to silence these aberrant T cells. We have shown that fibroblasts, transduced to secrete a myelin basic protein-derived peptide, abrogate disease in the murine experimental autoimmune encephalomyelitis model of multiple sclerosis, which we hypothesized using a low-zone tolerance mechanism. To determine the efficacy (or not) of this therapy in humans, we must ensure that patients receive comparable doses of therapeutic peptide. To this end, we have used liquid chromatography coupled to tandem mass spectrometry to detect a tryptic peptide, derived from the secreted therapeutic product, at nanomolar concentrations. Success depended on growing the transduced fibroblasts in defined PC-1 medium in the presence of a cocktail of protease inhibitors.

Donor major histocompatibility complex (MHC) peptides are presented by recipient MHC molecules during graft rejection.

Peptides from donor major histocompatibility complex (MHC) molecules were examined for their activation of allogeneically primed T cells. After immunization with either allogeneic spleen cells or a skin allograft, primed T cells proliferate in response to peptides derived from polymorphic regions of alpha and beta chains of class II allo-MHC molecules. The results demonstrate that presentation of donor-MHC peptides by host-derived antigen-presenting cells is a common event in vivo. Thus, self-restricted T cell recognition of processed alloantigens may play a critical role in transplantation. An in-depth understanding of this response may result in the development of additional molecular therapies to combat allograft rejection.

Molecular characterization of the C3HfB/HeN H-2Kkm2 mutation. Implications for the molecular basis of alloreactivity.

The C3HfB/HeN (C3Hf) mouse strain expresses an H-2Kk molecule, previously denoted H-2Kkv1, that is structurally and functionally distinct from H-2Kk of the parental C3H strain. By molecular genetic analysis, we demonstrate that the C3Hf H-2K gene carries a homozygous coding region mutation relative to the C3H allele, revealing that C3Hf meets the requirements for assignment of a mutant haplotype, H-2km2. C3Hf H-2Kkm2 bears a single clustered substitution of four nucleotides within 14 contiguous nucleotides in exon 3. Since this sequence also is present intact at the homologous position in H-2Dk of both C3H and C3Hf, the origin of the H-2Kkm2 mutation is consistent with a nonreciprocal sequence transfer from the H-2Dk donor gene, analogous to the mechanism proposed for generation of the H-2Kb mutations. The H-2Kkm2 mutation encodes three clustered amino acid substitutions, at positions 95, 98, and 99, that map to one of the large beta strands at the bottom of the peptide antigen binding cleft of the H-2Kkm2 molecule. The nature and location of these amino acid substitutions are unique relative to any other known H-2 mutant or HLA variant, and underscore the importance of the beta-pleated sheet in influencing CTL recognition. These results indicate that H-2Kkm2 alloantigenicity may derive largely from altered presentation of self cellular peptides.

Expression and T cell recognition of hybrid antigens with amino-terminal domains encoded by Qa-2 region of major histocompatibility complex and carboxyl termini of transplantation antigens.

Coding potential of the Q6 gene from the Qa-2a region of BALB/c Crgl mice was analyzed by a combination of hybrid class I gene construction and DNA-mediated gene transfer. Recombinant genes were created by exon shuffling of the 5' coding region of the Q6 gene and the 3' coding region of a gene encoding a transplantation antigen (Kd, Dd, or Ld), or the inverse. Some of these hybrid class I genes were expressed in the transfected mouse fibroblasts (L cells). The hybrid class I molecules encoded by the 5' end of the Q6 gene and the 3' end of the Ld gene precipitated as 45,000 mol wt molecules associated with beta 2-microglobulin. The expression of the hybrid proteins indicates that 926 basepairs of the 5' flanking region upstream of the structural Q6 gene contain a promoter that functions as a transcription initiation site in L cells. The 3' portion of the Q6 gene appears to be responsible for the lack of cell surface expression of the intact Q6 and the hybrid Ld/Q6 genes in mouse fibroblasts. Accordingly, this portion of the Q6 class I gene may play a regulatory role in tissue-specific expression. Serological analyses of hybrid Q6 proteins suggested that Q6 may be a structural gene for CR (H-2 crossreactive) antigen found normally on subpopulations of lymphocytes. If this identification is correct, Q6 gene will define a new category of class I genes encoding approximately 40,000 mol wt molecules and carrying a characteristic truncated cytoplasmic tail. Analysis of L cells transfected with Q6 hybrid genes demonstrated also that the cytotoxic T cells specific for Qa-2a region-coded antigens recognize the amino-terminal alpha 1-alpha 2 domain of Q6 fusion products. This recognition can be blocked by anti-Qa-2a alloantiserum and monoclonal antibodies reactive with the alpha 3-beta 2-microglobulin portion of the Q6 hybrids. We propose that the structural requirements for the anti-Qa-2a cytotoxic T lymphocyte-specific epitopes on target molecules are the same as for anti-H-2-alloreactive cytotoxic T lymphocyte determinants on transplantation antigens and that the mechanism of target recognition is similar in both cases. This interpretation is consistent with the following structural similarities found in both categories of class I molecules: (a) Kd and Q6 alpha 1-alpha 2 domains share serologically defined epitopes.(ABSTRACT TRUNCATED AT 400 WORDS)

Structure of murine Ia antigens. Two dimensional electrophoretic analyses and high pressure liquid chromatography tryptic peptide maps of products of the I-A and I-E subregions and of an associated invariant polypeptide.

We demonstrate that an invariant polypeptide, first described by Jones et al. (21), co-immunoprecipitates with our Ia molecules, that its interaction with Ia polypeptides varies with haplotype, and that it is not a precursor of the Aalpha, Abeta, Ealpha, or Ebeta. polypeptides. We also show that the polypeptides that we have previously characterized are contaminated with very little, if any, invariant protein. Further, we have used our high-pressure liquid chromatography tryptic peptide map technique to formally map the genes encoding Aalpha, Abeta, and Ebeta to the I-A subregion using recombinant and F1 hybrid mice.

Immunogenicity and tolerogenicity of self-major histocompatibility complex peptides.

Mechanisms involved in self-antigen processing and presentation are crucial in understanding the induction of self-tolerance in the thymus. We examined the immunogenicity of determinants from major histocompatibility complex (MHC) molecules that are expressed in the thymus and have tested peptides derived from the polymorphic regions of class I and class II molecules. We found that two peptides corresponding to NH2 termini of the class II alpha and beta chains (Ak alpha 1-18 and Ak beta 1-16) could bind to self-Ak molecules with high affinity and, surprisingly, were immunogenic in that they could elicit strong proliferative T cell responses in B10.A mice (Ak, Ek). Neonatal injection of peptide Ak beta 1-16 resulted in complete unresponsiveness to this peptide at 8 wk of age showing that these T cells were susceptible to tolerance induction. We have also tested certain class I MHC peptides and showed that some can interact efficiently with class II MHC peptides to induce an autoreactive T cell proliferative response. Among these class I peptides is one (Dd 61-85) that has the capacity to bind to self-Ia without being immunogenic, and therefore represents an MHC determinant that had induced thymic self-tolerance. We conclude that some self-MHC molecules can be processed into peptides that can be presented in the context of intact class II molecules at the surface of antigen-presenting cells. Autoreactive T cells recognizing optimally processed self-peptide/MHC complexes are eliminated during development, whereas other potentially autoreactive T cells escape clonal inactivation or deletion. Incomplete tolerance to self-antigens enriches the T cell repertoire despite the fact that such T cells may eventually become involved in autoimmune disease.

High dives and parallel plans: Relationships between medical student elective strategies and residency match outcomes.

BACKGROUND: Medical students are anxious about not getting a preferred residency position. We described elective patterns of two recent cohorts and examined associated match outcomes. METHODS: We conducted a retrospective review of the final-year electives of all students who participated in the residency match (first iteration) at one school for 2017 and 2018. We categorized elective patterns and associated them with aggregated match outcomes. We examined high-demand/low-supply (HDLS) disciplines separately. RESULTS: We described three elective patterns: High Dive, Parallel Plan(s), and No Clear Pattern. Many students had High Dive and Parallel Plans patterns; only a few showed No Clear Pattern. Match rates for High Dive and Parallel Plan patterns were high but many students matched to Family and Internal Medicine. When we separated out HDLS predominance, the match rate remained high but a significant number matched to disciplines in which they did not have a majority of electives. Most High Dive and Parallel Plan students who went unmatched did so with HDLS discipline electives. CONCLUSION: Many students chose High Dive and Parallel Plan strategies to both high-capacity and HDLS disciplines. Match rates were high for both patterns but students also matched to non-primary disciplines. Back-up planning may reside in the entire application, and not just electives selection.

CONTEXTE: Les étudiants en médecine sont anxieux à l'idée de ne pas obtenir le poste de résidence souhaité. Nous avons décrit les profils de stages à optionde deux cohortes récentes et examiné les résultats des jumelages associés. MÉTHODES: Nous avons mené une évaluation rétrospective des stages à option d'externat senior effectués par l'ensemble des étudiants qui ont participé au jumelage de résidence (premier tour) dans un programme de médecine pour 2017 et 2018. Nous avons classé les profils de stage et les avons associés aux résultats de jumelage agrégés. Nous avons examiné les disciplines à demande élevée et à offre faible (DEOF) séparément. RÉSULTATS: Nous avons décrit trois profils de stages à option : le « grand saut ¼, le plan parallèle B et aucun schéma précis. De nombreux étudiants présentaient des profils de type « grand saut ¼ et plans parallèles. Seuls quelques-uns ne présentaient aucun profil précis. Les taux de jumelage pour les schémas grand saut et plan parallèle étaient élevés, mais de nombreux étudiants étaient jumelés à Médecine familiale et Médecine interne. Quand nous avons séparé la prédominance DEOF, le taux de jumelage restait élevé, mais un nombre important d'étudiants obtenaient un poste dans des disciplines pour lesquelles ils n'avaient pas fait une majorité de stages à option. La plupart des étudiants avec profils « grand saut ¼ et plan parallèle qui n'avaient pas été jumelés avaient fait des stages à option dans des disciplines DEOF. CONCLUSION: De nombreux étudiants avaient choisi des stratégies « grand saut ¼ et plan parallèle pour des disciplines à haute capacité ainsi que des disciplines DEOF. Les taux de jumelage étaient élevés pour les deux profils, mais les étudiants se jumelaient également à des disciplines autres que leur premier choix. Une solution de rechange peut se trouver dans l'ensemble du processus, et non pas seulement dans la sélection des stages à option.

A randomised controlled trial of SMS messaging and calendar reminders to improve vaccination timeliness in infants.

BACKGROUND: The effectiveness of SMS reminders in improving vaccination coverage has been assessed previously, with effectiveness varying between settings. However, there are very few studies on their effect on the timeliness of vaccination. DESIGN: Unblinded, randomised controlled trial with blocked sampling. METHODS: 1594 Australian infants and young children were recruited to assess the impact of (1) SMS reminders only, (2) a personalised calendar, (3) SMS reminder and personalised calendar and (4) no intervention, on receipt of vaccine within 30 days of the due date. Outcomes were measured for receipt of vaccines due at 2, 4, 6, 12 and 18 months of age. A post-hoc assessment was also conducted of the impact of a new national "No jab No Pay" policy introduced during the trial, which removed philosophical objections as an exemption for financial penalties for non-vaccination. RESULTS: There was a statistically significant improvement in on-time vaccination only at the 12 month schedule point amongst infants who received SMS reminders alone (RR 1.09, 95% CI 1.01-1.18) or in combination with a personalised calendar (1.11, CI 1.03-1.20) compared to controls. This impact was limited to participants who had received one or more previous doses late. No statistically significant impacts of calendar interventions alone were seen. There was a high rate of on-time compliance amongst control participants - 95%, 86%, 80%, 74% at the 4, 6, 12 and 18 month schedule points respectively, which increased more than 10 percentage points after implementation of the "No Jab, No Pay" policy. CONCLUSIONS: SMS reminders are more effective in improving timeliness where pre-existing compliance is lower, but the 18 month schedule point appeared to be less amenable to intervention. Australia and New Zealand Clinical Trial Registration No. ACTRN12614000970640.

Identification of a BALB/c H-2Ld gene by DNA-mediated gene transfer.

Gene transfer and immunoselection were used in the identification of a BALB/c genomic clone containing an H-2Ld gene (clone 27.5). Transformation of thymidine kinase-negative C3H mouse L cells with the cloned 27.5 DNA together with the herpes simplex virus tk gene produced transformants expressing Ld molecules detected by radioimmune assay with monoclonal hybridoma antibodies to Ld antigens. The foreign Ld gene products expressed by cloned mouse L cell transformants were shown to be virtually indistinguishable from BALB/c spleen Ld molecules by two-dimensional electrophoretic analysis of H-2Ld immunoprecipitates. These results indicate that the genomic clone 27.5 contains a functional BALB/c H-2Ld gene and demonstrate the usefulness of this approach for identifying the gene products encoded by cloned genes which are members of a multigene family. Furthermore, the ability to place cell-surface recognition molecules on the surfaces of foreign cells provides a powerful opportunity for functional analyses of these molecules.