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BackgroundChest radiographs are used for diagnosis and severity assessment in tuberculosis (TB). The extent of disease as determined by smear grade and cavitation as a binary measure can predict 2-month smear results, but little has been done to determine whether radiological severity reflects the bacterial burden at diagnosis.MethodsPre-treatment chest x-rays from 1837 participants with smear-positive pulmonary TB enrolled into the REMoxTB trial (Gillespie et al., N Engl J Med 371:1577-87, 2014) were retrospectively reviewed. Two clinicians blinded to clinical details using the Ralph scoring system performed separate readings. An independent reader reviewed discrepant results for quality assessment and cavity presence. Cavitation presence was plotted against time to positivity (TTP) of sputum liquid cultures (MGIT 960). The Wilcoxon rank sum test was performed to calculate the difference in average TTP for these groups. The average lung field affected was compared to log 10 TTP by linear regression. Baseline markers of disease severity and patient characteristics were added in univariable regression analysis against radiological severity and a multivariable regression model was created to explore their relationship.ResultsFor 1354 participants, the median TTP was 117 h (4.88 days), being 26 h longer (95% CI 16-30, p

Nearly every modern Olympic Games has brought astonished comments and criticism of the body sizes of female gymnasts. The comments from laypersons, scientists, journalists, and physicians too often imply that these diminutive athletes are unusually small and possibly unhealthy. Purpose: An extended and updated analysis of the sizes of U.S. female Olympic gymnasts including the 2012 and 2016 Olympic Games. Methods: Official public records from the US Olympic Committee and USA Gymnastics of Olympic team members were assessed including height, mass, age, body-mass index (BMI) and team performance rankings. Sixteen Olympic teams with a total of 123 team positions including the alternates were assessed. Trend analyses were conducted using linear and polynomial models. Results: Analyses indicated that since 1956, height, mass, age, and BMI declined at first and then increased, with the exceptions of height and rank. Best regression fits were obtained via 2nd order polynomial equations. Height and rank showed a downward trend throughout the historical period. Conclusion: Female Olympic gymnasts were getting smaller through approximately the 1980s and early 1990s. An upward trend in size variables was then observed through 2008. The addition of the 2012 and 2016 Olympic Games data showed that height shifted to a decline from a slight upward trend, and rank continued to decline throughout the historical period.

Discovery learning is problem-based learning with minimal guidance. Critical thinking and life-long learning skills can be developed through discovery learning. [ABSTRACT FROM AUTHOR]

Tarsal navicular fractures require an accurate and timely diagnosis to prevent costly and disabling complications. Diagnosis requires a thorough clinical evaluation that focuses on the patient's history, particularly his or her training regimen, and diet--as was the case with these 17-year-old girls. Plain radiography, ultrasound, bone scintigraphy, MRI, and CT help make a definitive diagnosis. Treatment of low-risk fractures involves relative rest and cessation of the precipitating activity. High-risk fractures often require non--weigt-bearing immobilization, coupled with therapy, and may require surgery. [ABSTRACT FROM AUTHOR]

The J-motion squat--J refers to the trajectory of the hip during the squat--is a dynamic action combining the benefits of front and parallel squatting. The J-motion squat accentuates pelvic movement and enables the lifter to better utilize the hamstrings for further strength and power development. We describe the J-motion squat and provide a review of the practical benefits of teaching it as an ancillary lift within training programs for power athletes. [ABSTRACT FROM AUTHOR]

The Health Insurance Portability and Accountability Act (HIPAA) was enacted on August 21, 1996. Its fundamental purpose was to improve both the portability and the continuity of health insurance coverage. Title II of the act, intended to reduce paperwork, contained a clause called the Privacy Rule. The Privacy Rule is responsible for much confusion and controversy, particularly in collegiate sport settings. This paper identifies issues with the HIPAA Privacy Rule and suggests methods with which collegiate sport professionals can deal with those issues. [ABSTRACT FROM AUTHOR]

Rowing has a long, storied history. It is a popular competitive and recreational sport around the world. Whether on the water, in a boat, or on a rowing machine in a fitness center, rowing has long been championed by physicians and fitness experts as an excellent means of developing physical conditioning. Many sport scholars and fitness experts are knowledgeable about the physiological benefits of rowing and about how to design effective exercise programs, but they lack general historical knowledge about the sport. The purpose of this paper is to provide a useful pathfinder for resources on rowing, with an aim toward providing greater awareness of the sport. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To evaluate the reliability and variability of repeated measurements of dynamic and static lumbar muscle endurance. DESIGN AND SETTING: Participants performed an isometric lumbar-extension strength test followed by 2 trials of 4 separate lumbar muscular-endurance tests (with a 24-hour rest period between tests). Data were collected at a university musculoskeletal research laboratory. SUBJECTS: Eight healthy, physically active volunteers (5 men, 3 women; age = 25.9 +/- 4.3 years; height = 169.0 +/- 4.6 cm; mass = 73.9 +/- 33.1 kg) participated in this investigation. MEASUREMENTS: We initially tested each participant's isometric lumbar-extension peak torque on a lumbar-extension dynamometer. Static (holding time) and dynamic (repetitions) lumbar-endurance tests were subsequently performed on the lumbar-extension dynamometer and a horizontal roman chair. RESULTS: Interclass reliability was high for all endurance tests completed (r = 0.91 to 0.96, P

Objective: To present the unique case of a collegiate swimmer who experienced nearly 9 months of unresolved rib pain.Background: A 20-year-old collegiate swimmer was jumping up and down, warming up before a race, when she experienced pain in the area of her left lower rib cage. She completed the event and 2 additional events that day with moderate discomfort. The athlete was evaluated by a certified athletic trainer 3 days postinjury and followed up over the next 9 months with the team physician, a chiropractor, a nonsurgical sports medicine physician, and a thoracic surgeon.Differential Diagnosis: Intercostal strain, oblique strain, fractured rib, somatic dysfunction, hepatosplenic conditions, pleuritic chest pain, slipping rib syndrome.Treatment: The athlete underwent 4 months of conservative treatment (eg, activity modification, ice, ultrasound, hot packs, nonsteroidal anti-inflammatory drugs) after the injury, independently sought chiropractic intervention (12 treatments) 4 to 6 months postinjury, was referred to physical therapy (10 visits) by a nonsurgical sports medicine physician 6 to 8 months postinjury, and finally underwent surgical intervention 9 months after the onset of the initial symptoms.Uniqueness: Slipping rib syndrome was first described in 1919. However, many health care professionals who are involved with diagnosing and treating athletes and active individuals (eg, athletic trainers, physicians) are relatively unfamiliar with this musculoskeletal condition.Conclusions: It is important for clinicians and team physicians to familiarize themselves with and consider the diagnosis of slipping rib syndrome when assessing and managing individuals with persistent abdominal and/or thoracic pain. [ABSTRACT FROM AUTHOR]

Pregnancy in women with monogenic diabetes is potentially complex, with significant implications for both maternal and fetal health. Among these, maturity-onset diabetes of the young (MODY) stands out as a prevalent monogenic diabetes subtype frequently encountered in clinical practice. Each subtype of MODY requires a distinct approach tailored to the pregnancy, diverging from management strategies in non-pregnant individuals. Glucokinase MODY (GCK-MODY) typically does not require treatment outside of pregnancy, but special considerations arise when a woman with GCK-MODY becomes pregnant. The glycemic targets in GCK-MODY pregnancies are not exclusively dictated by the maternal/paternal MODY genotype but are also influenced by the genotype of the developing fetus. During pregnancy, the choice between sulfonylurea or insulin for treating hepatocyte nuclear factor 1-alpha (HNF1A)-MODY and HNF4A-MODY depends on the mother's specific circumstances and the available expertise. Management of other rarer MODY subtypes is individualized, with decisions made on a case-by-case basis. Therefore, a collaborative approach involving expert diabetes and obstetric teams is crucial for the comprehensive management of MODY pregnancies., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Antenatal corticosteroids (ACS) are widely prescribed to improve outcomes following preterm birth. Significant knowledge gaps surround their safety, long-term effects, optimal timing and dosage. Almost half of women given ACS give birth outside the "therapeutic window" and have not delivered over 7 days later. Overtreatment with ACS is a concern, as evidence accumulates of risks of unnecessary ACS exposure., Methods: The Consortium for the Study of Pregnancy Treatments (Co-OPT) was established to address research questions surrounding safety of medications in pregnancy. We created an international birth cohort containing information on ACS exposure and pregnancy and neonatal outcomes by combining data from four national/provincial birth registers and one hospital database, and follow-up through linked population-level data from death registers and electronic health records., Results and Discussion: The Co-OPT ACS cohort contains 2.28 million pregnancies and babies, born in Finland, Iceland, Israel, Canada and Scotland, between 1990 and 2019. Births from 22 to 45 weeks' gestation were included; 92.9% were at term (≥ 37 completed weeks). 3.6% of babies were exposed to ACS (67.0% and 77.9% of singleton and multiple births before 34 weeks, respectively). Rates of ACS exposure increased across the study period. Of all ACS-exposed babies, 26.8% were born at term. Longitudinal childhood data were available for 1.64 million live births. Follow-up includes diagnoses of a range of physical and mental disorders from the Finnish Hospital Register, diagnoses of mental, behavioural, and neurodevelopmental disorders from the Icelandic Patient Registers, and preschool reviews from the Scottish Child Health Surveillance Programme. The Co-OPT ACS cohort is the largest international birth cohort to date with data on ACS exposure and maternal, perinatal and childhood outcomes. Its large scale will enable assessment of important rare outcomes such as perinatal mortality, and comprehensive evaluation of the short- and long-term safety and efficacy of ACS., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Frier et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Reducing preterm birth and stillbirth and improving outcomes for babies born too soon is essential to reduce under-5 mortality globally. In the context of a rapidly evolving evidence base and problems with extrapolating efficacy data from high- to low-income settings, an assessment of the evidence for maternal and newborn interventions specific to low- and middle-income countries (LMICs) is required., Methods: A systematic review of the literature was done. We included all studies performed in LMICs since the Every Newborn Action Plan, between 2013 - 2018, which reported on interventions where the outcome assessed was reduction in preterm birth or stillbirth incidence and/or a reduction in preterm infant neonatal mortality. Evidence was categorised according to maternal or neonatal intervention groups and a narrative synthesis conducted., Results: 179 studies (147 primary evidence studies and 32 systematic reviews) were identified in 82 LMICs. 81 studies reported on maternal interventions and 98 reported on neonatal interventions. Interventions in pregnant mothers which resulted in significant reductions in preterm birth and stillbirth were (i) multiple micronutrient supplementation and (ii) enhanced quality of antenatal care. Routine antenatal ultrasound in LMICs increased identification of fetal antenatal conditions but did not reduce stillbirth or preterm birth due to the absence of services to manage these diagnoses. Interventions in pre-term neonates which improved their survival included (i) feeding support including probiotics and (ii) thermal regulation. Improved provision of neonatal resuscitation did not improve pre-term mortality rates, highlighting the importance of post-resuscitation care. Community mobilisation, for example through community education packages, was found to be an effective way of delivering interventions., Conclusions: Evidence supports the implementation of several low-cost interventions with the potential to deliver reductions in preterm birth and stillbirth and improve outcomes for preterm babies in LMICs. These, however, must be complemented by overall health systems strengthening to be effective. Quality improvement methodology and learning health systems approaches can provide important means of understanding and tackling implementation challenges within local contexts. Further pragmatic efficacy trials of interventions in LMICs are essential, particularly for interventions not previously tested in these contexts., Competing Interests: Competing interests: The authors completed the ICMJE Unified Competing Interest form (available upon request from the corresponding author), and declare no conflicts of interest., (Copyright © 2021 by the Journal of Global Health. All rights reserved.)

This protocol determines the fraction of a bacterial population that is viable and culturable, viable and non-culturable, or non-viable (dead). Each population is detected by isolating colonies on agar plates, performing direct counts, and staining for live or dead cells. Its application is limited to bacteria that are stainable and when permissible growth conditions are known. The quantitative data extracted allow for the detection of a viable but non-culturable (alive and non-dividing) population from a liquid culture. For complete details on the use and execution of this protocol, please refer to Stott et al. (2015)., Competing Interests: The authors declare no competing interests., (© 2021 The Authors.)

Background: Occasional smoking is defined as any smoking occurring on a less than daily basis. Social smoking, i.e. smoking primarily in social contexts, is a sub-group of occasional smoking. Data on occasional cigarette smoking and the subset of social smoking among third level students are limited., Objectives: (1) To determine prevalence of occasional/social smoking among third level students in an Irish university; (2) to evaluate students' attitudes to occasional/social smoking, including perceived benefits and harm; (3) to explore when students commenced occasional/social smoking, their reasons and continued smoking habits; and (4) to determine any influence of other factors, e.g. alcohol consumption, on occasional/social smoking., Methods: An anonymous online survey was distributed to undergraduates and postgraduates, using SurveyMonkey. Data were analysed in Microsoft Excel., Results: Of 18,407 students surveyed, 1310 (7.1%) responded;1267 (96.7%) provided adequate data for analysis. Of the 1267 students, 423 (33.4%) self-reported as current smokers of whom 106/1267 (8.4%) self-classified as daily smokers and 317/1267 (25%) as occasional smokers. The 25% of occasional smokers comprised 266/1267 (21%) social smokers and 51/1267 (4%) non-social smokers. Occasional smokers tended to start smoking earlier and think less about quitting than daily smokers. Of 423 current smokers, 386 (97.2%) reported that alcohol increased their smoking habits., Conclusion: Prevalence of self-reported occasional smoking among university students was higher than daily smoking. Most occasional smokers primarily smoked in social contexts. All current smokers reported that alcohol increased cigarette intake. Effective intervention campaigns tailored to determinants of occasional/social smoking are needed as part of induction to third level., (© 2020. Royal Academy of Medicine in Ireland.)

Globally the prevalence of gestational diabetes mellitus (GDM) is rising mainly due to the increase in maternal obesity. A number of different methods to screen for and diagnose GDM have been described although consensus on the preferred methods does not yet exist. GDM has significant short- and long-term health risks for the mother, developing fetus and the children born to mothers with GDM. Short-term risks for the fetus include macrosomia (excessive birthweight), shoulder dystocia, birth trauma, and hypoglycaemia in the immediate postpartum period. Long-term risks for offspring born to mothers with GDM include increased rates of childhood and adulthood obesity and an increased cardiometabolic risk. A number of pharmacological treatments for GDM have been identified, these include insulin and oral glucose-lowering drugs metformin and glibenclamide. Whilst these oral glucose-lowering drugs show similar short-term childhood outcomes to insulin there is increasing evidence that these drugs may have adverse long-term outcomes on children and adults exposed to the drugs in utero. Future research on treatments for GDM should include long-term follow- up of children exposed to glucose lowering medication in utero to determine the long-term cardiometabolic risk in the offspring born to mothers with GDM., (© 2020 The Authors. Prenatal Diagnosis published by John Wiley & Sons Ltd.)

Background: Twin pregnancy is associated with a threefold increase in perinatal death compared to singletons.  The objective of this study was to determine the risk of perinatal death in twins by week of gestation and to quantify the effect of known risk factors. Methods: A cohort analysis was performed using data from the Aberdeen Maternity and Neonatal Databank (AMND).  The exposure was gestational age at delivery and the primary outcome was perinatal death.  Adjusted hazard ratios (aHRs) for perinatal death according to gestational age at delivery were determined by multivariate Cox proportional hazards regression modelling with robust standard errors to account for clustering in the twin infants.  Confounders and risk factors quantified and adjusted for in the model included maternal age, smoking, parity, marital status and year of birth.  Kaplan-Meier time to event analysis was used to determine the differences in survival according to chorionicity and assisted reproduction technologies (ART) conception status. Results: The population comprised of 7,420 twin babies born between 1950 and 2013 in the Grampian area of Northern Scotland.  There were 272 stillbirths in the cohort (3.67%) and 273 neonatal deaths (3.68%). Compared to delivery at 37-38 weeks, delivery before 37 weeks was associated with a 2-fold increase in perinatal death. Monochorionic twins had a 2-fold increase in perinatal death compared to dichorionic twins (aHR 2.15, 95% CI 1.60-2.90). Twins conceived by ART did not have a greater risk of perinatal death compared to those naturally conceived (aHR 1.21, 95% CI 0.87-1.68) Conclusion:  This study suggests that delivery of twins at 37-38 weeks is associated with the lowest risk of perinatal death., Competing Interests: No competing interests were disclosed.

Objective: To inform feasibility and design of a future randomised controlled trial (RCT) using brain functional MRI (fMRI) to determine the mechanism of action of gabapentin in managing chronic pelvic pain (CPP) in women., Design: Mechanistic study embedded in pilot RCT., Setting: University Hospital., Participants: Twelve women (18-50 years) with CPP and no pelvic pathology (follow-up completed March 2014)., Intervention: Oral gabapentin (300-2700 mg) or matched placebo., Outcome Measures: After 12 weeks of treatment, participants underwent fMRI of the brain (Verio Siemens 3T MRI) during which noxious heat and punctate stimuli were delivered to the pelvis and arm. Outcome measures included pain (visual analogue scale), blood oxygen level dependent signal change and a semi-structured acceptability questionnaire at study completion prior to unblinding., Results: Full datasets were obtained for 11 participants. Following noxious heat to the abdomen, the gabapentin group (GG) had lower pain scores (Mean: 3.8 [SD 2.2]) than the placebo group (PG) (Mean: 5.8 [SD 0.9]). This was also the case for noxious heat to the arm with the GG having lower pain scores (Mean: 2.6 [SD 2.5]) than the PG (Mean: 6.2 [SD 1.1]). Seven out of 12 participants completed the acceptability questionnaire. 71% (five out of seven) described their participation in the fMRI study as positive; the remaining two rated it as a negative experience., Conclusions: Incorporating brain fMRI in a future RCT to determine the mechanism of action of gabapentin in managing CPP in women was feasible and acceptable to most women., Trial Registration Number: ISRCTN70960777., Competing Interests: Competing interests: The funders did not have any influence on the study design, data collection, analysis or interpretation of results., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. Published by BMJ.)

Background: International research has focused on screening and mass media campaigns to promote earlier patient presentation and detect lung cancer earlier. This trial tested the effect of a behavioural intervention in people at increased risk of lung cancer on help-seeking for respiratory symptoms., Methods: Parallel, individually randomised controlled trial. Eligible participants were long-term smokers with at least 20 pack-years, aged 55 and above. The CHEST intervention entailed a consultation to discuss and implement a self-help manual, followed by self-monitoring reminders to encourage help-seeking for respiratory symptoms. The control group received a brief discussion about lung health. Both groups had baseline spirometry. Telephone randomisation was conducted, 1:1, stratified Medical Research Council (MRC) dyspnoea score and general practice. Participants could not be blinded; data extraction and statistical analyses were performed blinded to group assignment. The primary outcome was respiratory consultation rates., Results: We randomised 551 participants (274 intervention, 277 control) from whom the primary outcome was determined for 542 (269 intervention, 273 control). There was a 40% relative increase in respiratory consultations in the intervention group: (adjusted rates (95% CI) intervention 0.57 (0.47 to 0.70), control 0.41 (0.32 to 0.52), relative rate 1.40 (1.08 to 1.82); p=0.0123). There were no significant differences in time to first respiratory consultation, total consultation rates or measures of psychological harm. The incremental cost-effectiveness ratio was $A1289 per additional respiratory consultation., Conclusions: A behavioural intervention can significantly increase consulting for respiratory symptoms in patients at increased risk of lung cancer. This intervention could have an important role in primary care as part of a broader approach to improve respiratory health in patients at higher risk., Trial Registration Number: Australian New Zealand Clinical Trial Registry (1261300039 3752). This was registered pre-results., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Preterm delivery is a major global public health challenge. The objective of this study was to determine how preterm delivery rates differ in a country with a very high human development index and to explore rural vs urban environmental and socioeconomic factors that may be responsible for this variation., Material and Methods: A population-based study was performed using data from the Swedish Medical Birth Register from 1998 to 2013. Sweden was chosen as a model because of its validated, routinely collected data and availability of individual social data. The total population comprised 1 335 802 singleton births. A multiple linear regression was used to adjust gestational age for known risk factors (maternal smoking, ethnicity, maternal education, maternal age, height, fetal sex, maternal diabetes, maternal hypertension, and parity). A second and a third model were subsequently fitted allowing separate intercepts for each municipality (as fixed or random effects). Adjusted gestational ages were converted to preterm delivery rates and mapped onto maternal residential municipalities. Additionally, the effects of six rural vs urban environmental and socioeconomic factors on gestational age were tested using a simple weighted linear regression., Results: The study population preterm delivery rate was 4.12%. Marked differences from the overall preterm delivery rate were observed (rate estimates ranged from 1.73% to 6.31%). The statistical significance of this heterogeneity across municipalities was confirmed by a chi-squared test (P < 0.001). Around 20% of the gestational age variance explained by the full model (after adjustment for known variables described above) could be attributed to municipality-level effects. In addition, gestational age was found to be longer in areas with a higher fraction of built-upon land and other urban features., Conclusions: After adjusting for known risk factors, large geographical differences in rates of preterm delivery remain. Additional analyses to look at the effect of environmental and socioeconomic factors on gestational age found an increased gestational age in urban areas. Future research strategies could focus on investigating the urbanity effect to try to explain preterm delivery variation across countries with a very high human development index., (© 2018 The Authors. Acta Obstetricia et Gynecologica Scandinavica published by John Wiley & Sons Ltd on behalf of Nordic Federation of Societies of Obstetrics and Gynecology (NFOG).)

Key Content: Twin pregnancies are associated with a three-fold greater perinatal mortality than singleton pregnancies. Prematurity is a main contributor, with 50% of twin pregnancies delivering before 37 weeks and 10% delivering before 32 weeks of gestation.The aetiology of preterm delivery in twin pregnancies is likely multifactorial and different from that of singletons.Cervical cerclage reduces preterm birth rates in singletons but has mixed results in twins with some studies showing harm.The use of progesterone to prevent preterm birth in singletons has conflicting results and has not been proven to prevent preterm birth in twins. Studies continue to determine whether the cervical pessary is effective in preventing preterm birth in multiple pregnancies.There is a paucity of data available on the prevention of preterm birth in triplets/higher order multiples but similar principles to twin pregnancy apply., Learning Objectives: To review the burden of preterm birth in multiple pregnancy.To understand the methods available for preventing preterm birth in multiple pregnancies and the evidence surrounding the use of each one.To be aware of the use of the Arabin pessary.

Globally, preterm birth rates are rising and have a significant impact on neonatal morbidity and mortality. Preterm birth remains difficult to prevent and a number of strategies for preterm birth prevention (progesterone, cervical pessaries, cervical cerclage, tocolytics, and antibiotics) have been identified. While some of these show more promise, there is a paucity of evidence regarding the long-term effects of these strategies on childhood outcomes. Strategies used to improve the health of babies if born preterm, such as antenatal magnesium sulfate for fetal neuroprotection and antenatal corticosteroids for fetal lung maturation, show evidence of short-term benefit but lack large-scale follow-up data of long-term childhood outcomes. Future research on preterm birth interventions should include long-term follow-up of the children, ideally with similar outcome measures to allow for future meta-analyses., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Lung cancer has one of the lowest survival outcomes of any cancer because over two-thirds of patients are diagnosed when curative treatment is no longer possible, partly due to later presentation with symptoms to a healthcare provider., Objective: To explore the theoretical underpinning of the Scottish CHEST intervention in participants randomized to the intervention group within the CHEST Australia trial., Methods: A purposive maximum variation sample of participants who received the intervention in the CHEST trial in Perth, Western Australia (N = 13) and Melbourne, Victoria, (N = 7) were interviewed. Patients were asked about their experience of the CHEST consultation, their recall of the main messages, their symptom appraisal and issues relating to help seeking when they develop symptoms. Thematic analysis was conducted to draw common themes between the participants., Results: We identified themes consistent with the theoretical basis of the CHEST intervention. Barriers to consultation identified in the CHEST Australia trial participants were smoker stigmatization, guilt, fatalism and symptom normalization. We identified a general perceived mistrust of GPs based on previous negative experiences of visiting their GP in relation to their smoking. The intervention tackled barriers around lecturing and feelings of guilt and stigma related to smoking. We identified expected effects on salience and personal relevance of symptoms. Participants reported a clearer understanding of what to look out for and when to take action after the CHEST intervention., Conclusions: These findings suggest that the CHEST Australia intervention is achieving the desired objectives at the qualitative level through the proposed theoretical mechanisms., (© The Author 2017. Published by Oxford University Press.)

Background: There is a paucity of evidence regarding long-term outcomes of late preterm (34-36 weeks) and early term (37-38 weeks) delivery.  The objective of this systematic review was to assess long-term cognitive outcomes of children born at these gestations. Methods: Four electronic databases (Medline, Embase, clinicaltrials.gov and PsycINFO) were searched.  Last search was 5 th August 2016.   Studies were included if they reported gestational age, IQ measure and the ages assessed.  The protocol was registered with the International prospective register of systematic reviews (PROSPERO Record CRD42015015472).  Two independent reviewers assessed the studies.  Data were abstracted and critical appraisal performed of eligible papers. Results: Of 11,905 potential articles, seven studies reporting on 41,344 children were included.  For early term births, four studies (n = 35,711) consistently showed an increase in cognitive scores for infants born at full term (39-41 weeks) compared to those born at early term (37-38 weeks) with increases for each week of term (difference between 37 and 40 weeks of around 3 IQ points), despite differences in age of testing and method of IQ/cognitive testing.  Four studies (n = 5644) reporting childhood cognitive outcomes of late preterm births (34 - 36 weeks) also differed in study design (cohort and case control); age of testing; and method of IQ testing, and found no differences in outcomes between late preterm and term births, although risk of bias was high in included studies. Conclusion:  Children born at 39-41 weeks have higher cognitive outcome scores compared to those born at early term (37-38 weeks).  This should be considered when discussing timing of delivery.  For children born late preterm, the data is scarce and when compared to full term (37-42 weeks) did not show any difference in IQ scores., Competing Interests: Competing interests: No competing interests were disclosed.

Background: Although starch consists of large macromolecules composed of glucose units linked by α-1,4-glycosidic linkages with α-1,6-glycosidic branchpoints, variation in starch structural and functional properties is found both within and between species. Interest in starch genetics is based on the importance of starch in food and industrial processes, with the potential of genetics to provide novel starches. The starch metabolic pathway is complex but has been characterized in diverse plant species, including pea., Results: To understand how allelic variation in the pea starch metabolic pathway affects starch structure and percent amylose, partial sequences of 25 candidate genes were characterized for polymorphisms using a panel of 92 diverse pea lines. Variation in the percent amylose composition of extracted seed starch and (amylopectin) chain length distribution, one measure of starch structure, were characterized for these lines. Association mapping was undertaken to identify polymorphisms associated with the variation in starch chain length distribution and percent amylose, using a mixed linear model that incorporated population structure and kinship. Associations were found for polymorphisms in seven candidate genes plus Mendel's r locus (which conditions the round versus wrinkled seed phenotype). The genes with associated polymorphisms are involved in the substrate supply, chain elongation and branching stages of the pea carbohydrate and starch metabolic pathways., Conclusions: The association of polymorphisms in carbohydrate and starch metabolic genes with variation in amylopectin chain length distribution and percent amylose may help to guide manipulation of pea seed starch structural and functional properties through plant breeding.

The Gram-positive pathogen Clostridium perfringens possesses type IV pili (TFP), which are extracellular fibers that are polymerized from a pool of pilin monomers in the cytoplasmic membrane. Two proteins that are essential for pilus functions are an assembly ATPase (PilB) and an inner membrane core protein (PilC). Two homologues each of PilB and PilC are present in C. perfringens , called PilB1/PilB2 and PilC1/PilC2, respectively, along with four pilin proteins, PilA1 to PilA4. The gene encoding PilA2, which is considered the major pilin based on previous studies, is immediately downstream of the pilB2 and pilC2 genes. Purified PilB2 had ATPase activity, bound zinc, formed hexamers even in the absence of ATP, and bound the second messenger molecule cyclic di-GMP (c-di-GMP). Circular dichroism spectroscopy of purified PilC2 indicated that it retained its predicted degree of alpha-helical secondary structure. Even though no direct interactions between PilB2 and PilC2 could be detected in vivo or in vitro even in the presence of c-di-GMP, high levels of expression of a diguanylate cyclase from C. perfringens (CPE1788) stimulated polymerization of PilA2 in a PilB2- and PilC2-dependent manner. These results suggest that PilB2 activity is controlled by c-di-GMP levels in vivo but that PilB2-PilC2 interactions are either transitory or of low affinity, in contrast to results reported previously from in vivo studies of the PilB1/PilC1 pair in which PilC1 was needed for polar localization of PilB1. This is the first biochemical characterization of a c-di-GMP-dependent assembly ATPase from a Gram-positive bacterium. IMPORTANCE Type IV pili (TFP) are protein fibers involved in important bacterial functions, including motility, adherence to surfaces and host cells, and natural transformation. All clostridia whose genomes have been sequenced show evidence of the presence of TFP. The genetically tractable species Clostridium perfringens was used to study proteins involved in polymerizing the pilin, PilA2, into a pilus. The assembly ATPase PilB2 and its cognate membrane protein partner, PilC2, were purified. PilB2 bound the intracellular signal molecule c-di-GMP. Increased levels of intracellular c-di-GMP led to increased polymerization of PilA2, indicating that Gram-positive bacteria use this molecule to regulate pilus synthesis. These findings provide valuable information for understanding how pathogenic clostridia regulate TFP to cause human diseases., (Copyright © 2017 American Society for Microbiology.)

Athlete preparation and performance continue to increase in complexity and costs. Modern coaches are shifting from reliance on personal memory, experience, and opinion to evidence from collected training-load data. Training-load monitoring may hold vital information for developing systems of monitoring that follow the training process with such precision that both performance prediction and day-to-day management of training become adjuncts to preparation and performance. Time-series data collection and analyses in sport are still in their infancy, with considerable efforts being applied in "big data" analytics, models of the appropriate variables to monitor, and methods for doing so. Training monitoring has already garnered important applications but lacks a theoretical framework from which to develop further. As such, we propose a framework involving the following: analyses of individuals, trend analyses, rules-based analysis, and statistical process control.

Key Message: Advances have been made in our understanding of Ascochyta blight resistance genetics through mapping candidate genes associated with QTL regions and demonstrating the importance of epistatic interactions in determining resistance. Ascochyta blight disease of pea (Pisum sativum L.) is economically significant with worldwide distribution. The causal pathogens are Didymella pinodes, Phoma medicaginis var pinodella and, in South Australia, P. koolunga. This study aimed to identify candidate genes that map to quantitative trait loci (QTL) for Ascochyta blight field disease resistance and to explore the role of epistatic interactions. Candidate genes associated with QTL were identified beginning with 101 defence-related genes from the published literature. Synteny between pea and Medicago truncatula was used to narrow down the candidates for mapping. Fourteen pea candidate sequences were mapped in two QTL mapping populations, A26 × Rovar and A88 × Rovar. QTL peaks, or the intervals containing QTL peaks, for the Asc2.1, Asc4.2, Asc4.3 and Asc7.1 QTL were defined by four of these candidate genes, while another three candidate genes occurred within 1.0 LOD confidence intervals. Epistasis involving QTL × background marker and background marker × background marker interactions contributed to the disease response phenotypes observed in the two mapping populations. For each population, five pairwise interactions exceeded the 5% false discovery rate threshold. Two candidate genes were involved in significant pairwise interactions. Markers in three genomic regions were involved in two or more epistatic interactions. Therefore, this study has identified pea defence-related sequences that are candidates for resistance determination, and that may be useful for marker-assisted selection. The demonstration of epistasis informs breeders that the architecture of this complex quantitative resistance includes epistatic interactions with non-additive effects.

Gymnastics is noted for involving highly specialized strength, power, agility and flexibility. Flexibility is perhaps the single greatest discriminator of gymnastics from other sports. The extreme ranges of motion achieved by gymnasts require long periods of training, often occupying more than a decade. Gymnasts also start training at an early age (particularly female gymnasts), and the effect of gymnastics training on these young athletes is poorly understood. One of the concerns of many gymnastics professionals is the training of the spine in hyperextension-the ubiquitous 'arch' seen in many gymnastics positions and movements. Training in spine hyperextension usually begins in early childhood through performance of a skill known as a back-bend. Does practising a back-bend and other hyperextension exercises harm young gymnasts? Current information on spine stretching among gymnasts indicates that, within reason, spine stretching does not appear to be an unusual threat to gymnasts' health. However, the paucity of information demands that further study be undertaken.

Purpose: To investigate a new power-to-body-mass (BM) ratio 3-min all-out cycling test (3MT(%BM)) for determining critical power (CP) and finite work capacity above CP (W')., Methods: The gas-exchange threshold (GET), maximal oxygen uptake (VO2max), and power output evoking VO2max (W(peak)) and GET (W(GET)) for cycle ergometry were determined in 12 participants. CP and W' were determined using the original "linear factor" 3MT (3MT(rpm^2)) and compared with CP and W' derived from a procedure, the 3MT(%BM), using the subject's body mass and self-reported physical activity rating (PA-R), with values derived from linear regression of the work-time model and power-inverse-time model (1/time) data from 3 separate exhaustive square-wave bouts., Results: The VO2max, VO(2GET), W(peak), and W(GET) values estimated from PA-R and a non-exercise-regression equation did not differ (P > .05) from actual measurements. Estimates of CP derived from the 3MT(%BM) (235 ± 56 W), 3MT(rpm^2) (234 ± 62 W), work-time (231 ± 57 W), and 1/time models (230 ± 57 W) did not differ (F = 0.46, P = .72). Similarly, estimates of W' between all methods did not differ (F = 3.58, P = .07). There were strong comparisons of the 3MT(%BM) to 1/time and work-time models with the average correlation, standard error of the measurement, and CV% for critical power being .96, 8.74 W, and 4.64%, respectively., Conclusion: The 3MT(%BM) is a valid, single-visit protocol for determining CP and W'.

Tumor-targeted Salmonella offers a promising approach to the delivery of therapeutics for the treatment of cancer. The Salmonella strains used, however, must be stably attenuated in order to provide sufficient safety for administration. Approaches to the generation of attenuated Salmonella strains have included deletion of the msbB gene that is responsible for addition of the terminal myristol group to lipid A. In the absence of myristoylation, lipid A is no longer capable of inducing septic shock, resulting in a significant enhancement in safety. However, msbB Salmonella strains also exhibit an unusual set of additional physiological characteristics, including sensitivities to NaCl, EGTA, deoxycholate, polymyxin, and CO2. Suppressor mutations that compensate for these sensitivities include somA, Suwwan, pmrA (C), and zwf. We describe here methods for isolation of strains with compensatory mutations that suppress these types of sensitivities and techniques for determining their underlying genetic changes and analysis of their effects in murine tumor models.

Unlabelled: The ubiquitous aquatic bacterium Caulobacter crescentus is highly resistant to uranium (U) and facilitates U biomineralization and thus holds promise as an agent of U bioremediation. To gain an understanding of how C. crescentus tolerates U, we employed transposon (Tn) mutagenesis paired with deep sequencing (Tn-seq) in a global screen for genomic elements required for U resistance. Of the 3,879 annotated genes in the C. crescentus genome, 37 were found to be specifically associated with fitness under U stress, 15 of which were subsequently tested through mutational analysis. Systematic deletion analysis revealed that mutants lacking outer membrane transporters (rsaFa and rsaFb), a stress-responsive transcription factor (cztR), or a ppGpp synthetase/hydrolase (spoT) exhibited a significantly lower survival rate under U stress. RsaFa and RsaFb, which are homologues of TolC in Escherichia coli, have previously been shown to mediate S-layer export. Transcriptional analysis revealed upregulation of rsaFa and rsaFb by 4- and 10-fold, respectively, in the presence of U. We additionally show that rsaFa mutants accumulated higher levels of U than the wild type, with no significant increase in oxidative stress levels. Our results suggest a function for RsaFa and RsaFb in U efflux and/or maintenance of membrane integrity during U stress. In addition, we present data implicating CztR and SpoT in resistance to U stress. Together, our findings reveal novel gene targets that are key to understanding the molecular mechanisms of U resistance in C. crescentus., Importance: Caulobacter crescentus is an aerobic bacterium that is highly resistant to uranium (U) and has great potential to be used in U bioremediation, but its mechanisms of U resistance are poorly understood. We conducted a Tn-seq screen to identify genes specifically required for U resistance in C. crescentus. The genes that we identified have previously remained elusive using other omics approaches and thus provide significant insight into the mechanisms of U resistance by C. crescentus. In particular, we show that outer membrane transporters RsaFa and RsaFb, previously known as part of the S-layer export machinery, may confer U resistance by U efflux and/or by maintaining membrane integrity during U stress., (Copyright © 2015, American Society for Microbiology. All Rights Reserved.)

Introduction: Lung cancer is the most common cancer worldwide, with 1.3 million new cases diagnosed every year. It has one of the lowest survival outcomes of any cancer because over two-thirds of patients are diagnosed when curative treatment is not possible. International research has focused on screening and community interventions to promote earlier presentation to a healthcare provider to improve early lung cancer detection. This paper describes the protocol for a phase II, multisite, randomised controlled trial, for patients at increased risk of lung cancer in the primary care setting, to facilitate early presentation with symptoms of lung cancer., Methods/analysis: The intervention is based on a previous Scottish CHEST Trial that comprised of a primary-care nurse consultation to discuss and implement a self-help manual, followed by self-monitoring reminders to improve symptom appraisal and encourage help-seeking in patients at increased risk of lung cancer. We aim to recruit 550 patients from two Australian states: Western Australia and Victoria. Patients will be randomised to the Intervention (a health consultation involving a self-help manual, monthly prompts and spirometry) or Control (spirometry followed by usual care). Eligible participants are long-term smokers with at least 20 pack years, aged 55 and over, including ex-smokers if their cessation date was less than 15 years ago. The primary outcome is consultation rate for respiratory symptoms., Ethics and Dissemination: Ethical approval has been obtained from The University of Western Australia's Human Research Ethics Committee (RA/4/1/6018) and The University of Melbourne Human Research Committee (1 441 433). A summary of the results will be disseminated to participants and we plan to publish the main trial outcomes in a single paper. Further publications are anticipated after further data analysis. Findings will be presented at national and international conferences from late 2016., Trial Registration Number: Australian New Zealand Clinical Trial Registry ACTRN 1261300039 3752., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Athlete recovery-adaptation is crucial to the progress and performance of highly trained athletes. The purpose of this study was to assess peristaltic pulse dynamic compression (PPDC) in reducing short-term pressure-to-pain threshold (PPT) among Olympic Training Center athletes after morning training. Muscular tenderness and stiffness are common symptoms of fatigue and exercise-induced muscle microtrauma and edema. Twenty-four highly trained athletes (men = 12 and women = 12) volunteered to participate in this study. The athletes were randomly assigned to experimental (n = 12) and control (n = 12) groups. Pressure-to-pain threshold measurements were conducted with a manual algometer on 3 lower extremity muscles. Experimental group athletes underwent PPDC on both legs through computer-controlled circumferential inflated leggings that used a peristaltic-like pressure pattern from feet to groin. Pressures in each cell were set to factory defaults. Treatment time was 15 minutes. The control group performed the same procedures except that the inflation pump to the leggings was off. The experimental timeline included a morning training session, followed by a PPT pretest, treatment application (PPDC or control), an immediate post-test (PPT), and a delayed post-test (PPT) after the afternoon practice session. Difference score results showed that the experimental group's PPT threshold improved after PPDC treatment immediately and persisted the remainder of the day after afternoon practice. The control group showed no statistical change. We conclude that PPDC is a promising means of accelerating and enhancing recovery after the normal aggressive training that occurs in Olympic and aspiring Olympic athletes.

Starch phosphorylation is an important aspect of plant metabolism due to its role in starch degradation. Moreover, the degree of phosphorylation of starch determines its physicochemical properties and is therefore relevant for industrial uses of starch. Currently, starch is chemically phosphorylated to increase viscosity and paste stability. Potato cultivars with elevated starch phosphorylation would make this process unnecessary, thereby bestowing economic and environmental benefits. Starch phosphorylation is a complex trait which has been previously shown by antisense gene repression to be influenced by a number of genes including those involved in starch synthesis and degradation. We have used an association mapping approach to discover genetic markers associated with the degree of starch phosphorylation. A diverse collection of 193 potato lines was grown in replicated field trials, and the levels of starch phosphorylation at the C6 and C3 positions of the glucosyl residues were determined by mass spectrometry of hydrolyzed starch from tubers. In addition, the potato lines were genotyped by amplicon sequencing and microsatellite analysis, focusing on candidate genes known to be involved in starch synthesis. As potato is an autotetraploid, genotyping included determination of allele dosage. Significant associations (p < 0.001) were found with SNPs in the glucan water dikinase (GWD), starch branching enzyme I (SBEI) and the starch synthase III (SSIII) genes, and with a SSR allele in the SBEII gene. SNPs in the GWD gene were associated with C6 phosphorylation, whereas polymorphisms in the SBEI and SBEII genes were associated with both C6 and C3 phosphorylation and the SNP in the SSIII gene was associated with C3 phosphorylation. These allelic variants have potential as genetic markers for starch phosphorylation in potato.

Stress conditions, such as a block in fatty acid synthesis, signal bacterial cells to exit the cell cycle. Caulobacter crescentus FabH is a cell-cycle-regulated β-ketoacyl-acyl carrier protein synthase that initiates lipid biosynthesis and is essential for growth in rich media. To explore how C. crescentus responds to a block in lipid biosynthesis, we created a FabH-depletion strain. We found that FabH depletion blocks lipid biosynthesis in rich media and causes a cell cycle arrest that requires the alarmone (p)ppGpp for adaptation. Notably, basal levels of (p)ppGpp coordinate both a reduction in cell volume and a block in the over-initiation of DNA replication in response to FabH depletion. The gene ctrA encodes a master transcription factor that directly regulates 95 cell-cycle-controlled genes while also functioning to inhibit the initiation of DNA replication. Here, we demonstrate that ctrA transcription is (p)ppGpp-dependent during fatty acid starvation. CtrA fails to accumulate when FabH is depleted in the absence of (p)ppGpp due to a substantial reduction in ctrA transcription. The (p)ppGpp-dependent maintenance of ctrA transcription during fatty acid starvation initiated from only one of the two ctrA promoters. In the absence of (p)ppGpp, the majority of FabH-depleted cells enter a viable but non-culturable state, with multiple chromosomes, and are unable to recover from the miscoordination of cell cycle events. Thus, basal levels of (p)ppGpp facilitate C. crescentus' re-entry into the cell cycle after termination of fatty acid starvation., (© 2015 The Authors.)

Recent data indicate that cell cycle transcription in many alpha-Proteobacteria is executed by at least three conserved functional modules in which pairs of antagonistic regulators act jointly, rather than in isolation, to control transcription in S-, G2- or G1-phase. Inactivation of module components often results in pleiotropic defects, ranging from cell death and impaired cell division to fairly benign deficiencies in motility. Expression of module components can follow systemic (cell cycle) or external (nutritional/cell density) cues and may be implemented by auto-regulation, ancillary regulators or other (unknown) mechanisms. Here, we highlight the recent progress in understanding the molecular events and the genetic relationships of the module components in environmental, pathogenic and/or symbiotic alpha-proteobacterial genera. Additionally, we take advantage of the recent genome-wide transcriptional analyses performed in the model alpha-Proteobacterium Caulobacter crescentus to illustrate the complexity of the interactions of the global regulators at selected cell cycle-regulated promoters and we detail the consequences of (mis-)expression when the regulators are absent. This review thus provides the first detailed mechanistic framework for understanding orthologous operational principles acting on cell cycle-regulated promoters in other alpha-Proteobacteria., (© FEMS 2015. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Early-phase and preclinical studies suggest that moxifloxacin-containing regimens could allow for effective 4-month treatment of uncomplicated, smear-positive pulmonary tuberculosis., Methods: We conducted a randomized, double-blind, placebo-controlled, phase 3 trial to test the noninferiority of two moxifloxacin-containing regimens as compared with a control regimen. One group of patients received isoniazid, rifampin, pyrazinamide, and ethambutol for 8 weeks, followed by 18 weeks of isoniazid and rifampin (control group). In the second group, we replaced ethambutol with moxifloxacin for 17 weeks, followed by 9 weeks of placebo (isoniazid group), and in the third group, we replaced isoniazid with moxifloxacin for 17 weeks, followed by 9 weeks of placebo (ethambutol group). The primary end point was treatment failure or relapse within 18 months after randomization., Results: Of the 1931 patients who underwent randomization, in the per-protocol analysis, a favorable outcome was reported in fewer patients in the isoniazid group (85%) and the ethambutol group (80%) than in the control group (92%), for a difference favoring the control group of 6.1 percentage points (97.5% confidence interval [CI], 1.7 to 10.5) versus the isoniazid group and 11.4 percentage points (97.5% CI, 6.7 to 16.1) versus the ethambutol group. Results were consistent in the modified intention-to-treat analysis and all sensitivity analyses. The hazard ratios for the time to culture negativity in both solid and liquid mediums for the isoniazid and ethambutol groups, as compared with the control group, ranged from 1.17 to 1.25, indicating a shorter duration, with the lower bounds of the 95% confidence intervals exceeding 1.00 in all cases. There was no significant difference in the incidence of grade 3 or 4 adverse events, with events reported in 127 patients (19%) in the isoniazid group, 111 (17%) in the ethambutol group, and 123 (19%) in the control group., Conclusions: The two moxifloxacin-containing regimens produced a more rapid initial decline in bacterial load, as compared with the control group. However, noninferiority for these regimens was not shown, which indicates that shortening treatment to 4 months was not effective in this setting. (Funded by the Global Alliance for TB Drug Development and others; REMoxTB ClinicalTrials.gov number, NCT00864383.).

The association between assisted reproduction technologies (ART) and multiple pregnancy is well-established, with a multiple birth rate of 24% in ART pregnancies. Multiple pregnancy is associated with significantly increased maternal and perinatal morbidity and mortality, as well as increased costs to the National Health Service. Evidence relating to the obstetric outcomes of ART twins versus naturally conceived twins is discussed in this review. Methods to reduce the risk of multiple births including elective single embryo transfer and multifetal pregnancy reduction are also discussed., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

This study investigated the effects of peristaltic pulse dynamic compression (PPDC) on range-of-motion (ROM) changes in forward splits. Serious stretching usually involves discomfort and large time investments. Tissue structural changes and stretch tolerance have heretofore been considered the primary mechanisms of enhanced ROM. The PPDC treatment was computer controlled. Circumferential and segmented inflation pressures were induced by feet to hip leggings. Nine subjects, experienced in stretching and a forward split position, volunteered. The subjects were familiarized with the protocol and randomly assigned to an initial condition: experimental (PPDC), or control (CONT). The study involved a crossover design. Second conditions were tested within 1-5 days. All tests were 2 trials of right and left forward splits. Split flexibility was assessed by measuring the height of the anterior superior iliac spine of the rear leg from the floor. Pelvic posture was controlled by rear leg position. The PPDC treatment was 15 minutes of seated PPDC. The control condition was the same except that leggings were not inflated. Pressures of 5 cells in the leggings were set at factory defaults, 70 mm Hg sequentially. Difference score results indicated statistically significant (p ≤ 0.05) differences by condition and the condition by leg interaction. The rapid acute changes in ROM (PPDC: right 25.3%, left 33.3%; CONT: right 12.2%, left 1.0%) support the premise that changes in ROM were dependent on mechanisms other than tissue structural changes and/or stretch tolerance. PPDC provides a means of rapidly enhancing acute ROM requiring less discomfort and time.