The importance of place-kicking in Women's International Rugby Union.

Despite the growing popularity of women's rugby, there is a lack of research understanding the contribution of place-kicking to match outcomes. This study aims to establish the characteristics and contribution of place-kicking to women's international Rugby Union and evaluate the performance of place-kickers while accounting for factors that contribute to kick difficulty. Data from 674 place-kicks across 80 matches were analysed. A binomial generalised linear mixed model (GLMM) was used to predict the probability of kick success. 60.5% of place-kicks were successful, and they contributed 23.9% of all points scored; conversions accounted for 16.8% and penalties 7.1%. Kick success percentages for conversions (56.9%) and penalties (78.3%) significantly differed (p < 0.01). Kick distance and angle were significant (p < 0.01) predictors of kick success and the GLMM had a prediction accuracy of 73.6%. The performance rankings of kickers changed when comparing observed and expected success, highlighting the need to consider contextual factors contributing to kick difficulty when evaluating performance. The GLMM results provide valuable insights for coaches and players to make informed decisions, for example, whether to attempt a place-kick when a penalty is awarded, by enabling predictions of place-kick success. This could enhance a team's chances of winning matches.

Plasma levels of mannan-binding lectin-associated serine proteases are increased in type 1 diabetes patients with insulin resistance.

Activation of the lectin pathway of the complement system, as demonstrated by elevated levels of mannan-binding lectin proteins (MBL), contributes to vascular pathology in type 1 diabetes (T1D). Vascular complications are greatest in T1D individuals with concomitant insulin resistance (IR), however, whether IR amplifies activiation of the lectin pathway in T1D is unknown. We pooled pretreatment data from two RCTs and performed a cross-sectional analysis on 46 T1D individuals. We employed estimated glucose disposal rate (eGDR), a validated IR surrogate with cut-points of: <5.1, 5.1-8.7, and > 8.7 mg/kg/min to determine IR status, with lower eGDR values conferring higher degrees of IR. Plasma levels of MBL-associated proteases (MASP-1, MASP-2, and MASP-3) and their regulatory protein MAp44 were compared among eGDR classifications. In a subset of 14 individuals, we assessed change in MASPs and MAp44 following improvement in IR. We found that MASP-1, MASP-2, MASP-3, and MAp44 levels increased in a stepwise fashion across eGDR thresholds with elevated MASPs and MAp44 levels conferring greater degrees of IR. In a subset of 14 patients, improvement in IR was associated with significant reductions in MASPs, but not MAp44, levels. In conclusion, IR in T1D amplifies levels of MASP-1/2/3 and their regulator MAp44, and improvement of IR normalizes MASP-1/2/3 levels. Given that elevated levels of these proteins contribute to vascular pathology, amplification of the lectin pathway of the complement system may offer mechanistic insight into the relationship between IR and vascular complications in T1D.

Risk factors for pre-eclampsia in clinical practice guidelines: Comparison with the evidence.

OBJECTIVE: To compare pre-eclampsia risk factors identified by clinical practice guidelines (CPGs) with risk factors from hierarchical evidence review, to guide pre-eclampsia prevention. DESIGN: Our search strategy provided hierarchical evidence of relationships between risk factors and pre-eclampsia using Medline (Ovid), searched from January 2010 to January 2021. SETTING: Published studies and CPGs. POPULATION: Pregnant women. METHODS: We evaluated the strength of association and quality of evidence (GRADE). CPGs (n = 15) were taken from a previous systematic review. MAIN OUTCOME MEASURE: Pre-eclampsia. RESULTS: Of 78 pre-eclampsia risk factors, 13 (16.5%) arise only during pregnancy. Strength of association was usually 'probable' (n = 40, 51.3%) and the quality of evidence was low (n = 35, 44.9%). The 'major' and 'moderate' risk factors proposed by 8/15 CPGs were not well aligned with the evidence; of the ten 'major' risk factors (alone warranting aspirin prophylaxis), associations with pre-eclampsia were definite (n = 4), probable (n = 5) or possible (n = 1), based on moderate (n = 4), low (n = 5) or very low (n = 1) quality evidence. Obesity ('moderate' risk factor) was definitely associated with pre-eclampsia (high-quality evidence). The other ten 'moderate' risk factors had probable (n = 8), possible (n = 1) or no (n = 1) association with pre-eclampsia, based on evidence of moderate (n = 1), low (n = 5) or very low (n = 4) quality. Three risk factors not identified by the CPGs had probable associations (high quality): being overweight; 'prehypertension' at booking; and blood pressure of 130-139/80-89 mmHg in early pregnancy. CONCLUSIONS: Pre-eclampsia risk factors in CPGs are poorly aligned with evidence, particularly for the strongest risk factor of obesity. There is a lack of distinction between risk factors identifiable in early pregnancy and those arising later. A refresh of the strategies advocated by CPGs is needed.

Classifying Winning Performances in International Women's Rugby Union.

PURPOSE: The efficacy of isolated and relative performance indicators (PIs) has been compared in rugby union; the latter more effective at discerning match outcomes. However, this methodology has not been applied in women's rugby. The aim of this study was to identify PIs that maximize prediction accuracy of match outcome, from isolated and relative data sets, in women's rugby union. METHODS: Twenty-six PIs were selected from 110 women's international rugby matches between 2017 and 2022 to form an isolated data set, with relative data sets determined by subtracting corresponding opposition PIs. Random forest classification was completed on both data sets, and feature selection and importance were used to simplify models and interpret key PIs. Models were used in prediction on the 2021 World Cup to evaluate performance on unseen data. RESULTS: The isolated full model correctly classified 75% of outcomes (CI, 65%-82%), whereas the relative full model correctly classified 78% (CI, 69%-86%). Reduced respective models correctly classified 74% (CI, 65%-82%) and 76% (CI, 67%-84%). Reduced models correctly predicted 100% and 96% of outcomes for isolated and relative test data sets, respectively. No significant difference in accuracy was found between data sets. In the relative reduced model, meters made, clean breaks, missed tackles, lineouts lost, carries, and kicks from hand were significant. CONCLUSIONS: Increased relative meters made, clean breaks, carries, and kicks from hand and decreased relative missed tackles and lineouts lost were associated with success. This information can be utilized to inform physical and tactical preparation and direct physiological studies in women's rugby.

Performance indicators associated with match outcome within the United Rugby Championship.

OBJECTIVES: The aims of this study were to: i) identify performance indicators associated with match outcomes in the United Rugby Championship; ii) compare the efficacy of isolated and relative datasets to predict match outcome; and iii) investigate whether reduced statistical models can reproduce predictive accuracy. DESIGN: Retrospective analysis of key performance indicators in the United Rugby Championship. METHODS: Twenty-seven performance indicators were selected from 96 matches (2020-21 United Rugby Championship). Random forest classification was completed on isolated and relative datasets, using a binary match outcome (win/lose). Maximum relevance and minimum redundancy performance indicator selection was utilised to reduce models. In addition, models were tested on 53 matches from the 2021-22 season to ascertain prediction accuracy. RESULTS: Within the 2020-21 datasets, the full models correctly classified 83% of match performances for the relative dataset and 64% for isolated data, the equivalent reduced models classified 85% and 66% respectively. The reduced relative model successfully predicted 90% of match performances in the 21-22 season, highlighting that five performance indicators were significant: kicks from hand, metres made, clean breaks, turnovers conceded and scrum penalties. CONCLUSIONS: Relative performance indicators were more effective in predicting match outcomes than isolated data. Reducing features used in random forest classification did not degrade prediction accuracy, whilst also simplifying interpretation for practitioners. Increased kicks from hand, metres made, and clean breaks compared to the opposition, as well as fewer scrum penalties and turnovers conceded were all indicators of winning match outcomes within the United Rugby Championship.

Factors contributing to the change in thermoneutral maximal oxygen consumption after iso-intensity heat acclimation programmes.

The factors explaining variance in thermoneutral maximal oxygen uptake (V˙O2max) adaptation to heat acclimation (HA) were evaluated, with consideration of HA programme parameters, biophysical variables and thermo-physiological responses. Seventy-one participants consented to perform iso-intensity training (range: 45%-55% V˙O2max) in the heat (range: 30°C-38°C; 20%-60% relative humidity) on consecutive days (range: 5-days-14-days) for between 50-min and-90 min. The participants were evaluated for their thermoneutral V˙O2max change pre-to-post HA. Participants' whole-body sweat rate, heart rate, core temperature, perceived exertion and thermal sensation and plasma volume were measured, and changes in these responses across the programme determined. Partial least squares regression was used to explain variance in the change in V˙O2max across the programme using 24 variables. Sixty-three percent of the participants increased V˙O2max more than the test error, with a mean ± SD improvement of 2.6 ± 7.9%. A two-component model minimised the root mean squared error and explained the greatest variance (R2; 65%) in V˙O2max change. Eight variables positively contributed (P < 0.05) to the model: exercise intensity (%V˙O2max), ambient temperature, HA training days, total exposure time, baseline body mass, thermal sensation, whole-body mass losses and the number of days between the final day of HA and the post-testing day. Within the ranges evaluated, iso-intensity HA improved V˙O2max 63% of the time, with intensity - and volume-based parameters, alongside sufficient delays in post-testing being important considerations for V˙O2max maximisation. Monitoring of thermal sensation and body mass losses during the programme offers an accessible way to gauge the degree of potential adaptation.

Topical Negative Pressure Wound Dressing and Its Applications in the Hand-A Review of the Literature.

The use of topical negative pressure wound therapy (NPWT) has become increasingly popular in the management of complex wounds. There are many theories as to the mechanism of action of NPWT, but the essential components of the various systems remain consistent. There are many attractive potential properties of negative pressure dressings that lend themselves to the management of upper limb injuries. This article explores the technique of negative pressure wound dressing, the theories pertaining to mechanism of action, and the increasingly broad indications described for the use of NPWT in the hand. The literature pertaining to the efficacy of NPWT in general is also discussed.

Guidelines-similarities and dissimilarities: a systematic review of international clinical practice guidelines for pregnancy hypertension.

OBJECTIVE: This study aimed to review pregnancy hypertension clinical practice guidelines to inform international clinical practice and research priorities. STUDY ELIGIBILITY CRITERIA: Relevant national and international clinical practice guidelines, 2009-19, published in English, French, Dutch or German. STUDY APPRAISAL AND SYNTHESIS METHODS: Following published methods and prospective registration (CRD42019123787), a literature search was updated. CPGs were identified by 2 authors independently who scored quality and usefulness for practice (Appraisal of Guidelines for Research and Evaluation II instrument), abstracted data, and resolved any disagreement by consensus. RESULTS: Of note, 15 of 17 identified clinical practice guidelines (4 international) were deemed "clinically useful" and had recommendations abstracted. The highest Appraisal of Guidelines for Research and Evaluation II scores were from government organizations, and scores have improved over time. The following were consistently recommended: (1) automated blood pressure measurement with devices validated for pregnancy and preeclampsia, reflecting increasing recognition of the prevalence of white-coat hypertension and the potential usefulness of home blood pressure monitoring; (2) use of dipstick proteinuria testing for screening followed by quantitative testing by urinary protein-to-creatinine ratio or 24-hour urine collection; (3) key definitions and most aspects of classification, including a broad definition of preeclampsia (which includes proteinuria and maternal end-organ dysfunction, including headache and visual symptoms and laboratory abnormalities of platelets, creatinine, or liver enzymes) and a recognition that it can worsen after delivery; (4) preeclampsia prevention with aspirin; (5) treatment of severe hypertension, most commonly with intravenous labetalol, oral nifedipine, or intravenous hydralazine; (6) treatment for nonsevere hypertension when undertaken, with oral labetalol (in particular), methyldopa, or nifedipine, with recommendations against the use of renin-angiotensin-aldosterone inhibitors; (7) magnesium sulfate for eclampsia treatment and prevention among women with "severe" preeclampsia; (8) antenatal corticosteroids for preterm birth but not hemolysis, elevated liver enzymes, and low platelet count syndrome; (9) delivery at term for preeclampsia; (10) a focus on usual labor and delivery care but avoidance of ergometrine; and (11) an appreciation that long-term health complications are increased in incidence, mandating lifestyle change and risk factor modification. Lack of uniformity was seen in the following areas: (1) the components of a broad preeclampsia definition (specifically respiratory and gastrointestinal symptoms, fetal manifestations, and biomarkers), what constitutes severe preeclampsia, and whether the definition has utility because at present what constitutes severe preeclampsia by some guidelines that mandate proteinuria now defines any preeclampsia for most other clinical practice guidelines; (2) how preeclampsia risk should be identified early in pregnancy, and aspirin administered for preeclampsia prevention, because multivariable models (with biomarkers and ultrasonography added to clinical risk markers) used in this way to guide aspirin therapy can substantially reduce the incidence of preterm preeclampsia; (3) the value of calcium added to aspirin for preeclampsia prevention, particularly for women with low intake and at increased risk of preeclampsia; (4) emerging recommendations to normalize blood pressure with antihypertensive agents even in the absence of comorbidities; (5) fetal neuroprotection as an indication for magnesium sulfate in the absence of "severe" preeclampsia; and (6) timing of birth for chronic and gestational hypertension and preterm preeclampsia. CONCLUSION: Consistent recommendations should be implemented and audited. Inconsistencies should be the focus of research.

Photochemically Mediated Nickel-Catalyzed Synthesis of N-(Hetero)aryl Sulfamides.

A general method for the N-arylation of sulfamides with aryl bromides is described. The protocol leverages a dual-catalytic system, with [Ir(ppy)2(dtbbpy)]PF6 as a photosensitizer, NiBr2·glyme as a precatalyst, and 1,8-diazabicyclo(5.4.0)undec-7-ene (DBU) as a base, and proceeds at room temperature under visible light irradiation. Using these tactics, aryl boronic esters and aryl chlorides can be carried through the reaction untouched. The developed reactions efficiently engage simple bromoarenes and primary sulfamides in between 66% and quantitative yields. For more challenging substrates, such as secondary sulfamides, the reaction efficiency is documented. Thereby, these methods complement the known Buchwald-Hartwig coupling methods for N-arylation of sulfamides.

Photochemically-Mediated, Nickel-Catalyzed Synthesis of N-(Hetero)aryl Sulfamate Esters.

A general method is described for the coupling of (hetero)aryl bromides with O-alkyl sulfamate esters. The protocol relies on catalytic amounts of nickel and photoexcitable iridium complexes and proceeds under visible light irradiation at ambient temperature. This technology engages a broad range of simple and complex O-alkyl sulfamate ester substrates under mild conditions. Furthermore, it is possible to avoid undesirable N-alkylation, which was found to plague palladium-based protocols for N-arylation of O-alkyl sulfamate esters. These investigations represent the first use of sulfamate esters as nucleophiles in transition metal-catalyzed C-N coupling processes.

Lesson of the month 2: A choroid plexus papilloma manifesting as anorexia nervosa in an adult.

A Caucasian female previously diagnosed with anorexia nervosa was referred by psychiatric services to the general medical team. She presented with dehydration, vomiting, weakness, a body mass index of 13 kg/m2 and was treated with intravenous and enteral supplementation. During admission her vomiting worsened and she developed visual hallucinations and confabulation. Neurological examination demonstrated cerebellar signs and bilateral papilloedema on fundoscopy. Subsequent magnetic resonance imaging of the brain revealed a large fourth ventricular tumour causing obstructive hydrocephalus. The tumour was excised and histologically confirmed to be a choroid plexus papilloma. Postoperatively her neurological symptoms and negative feelings towards eating resolved.

ISG15 as a novel tumor biomarker for drug sensitivity.

Tumor cells are known to exhibit highly varied sensitivity to camptothecins (CPT; e.g., irinotecan and topotecan). However, the factors that determine CPT sensitivity/resistance are largely unknown. Recent studies have shown that the ubiquitin-like protein, IFN-stimulated gene 15 (ISG15), which is highly elevated in many human cancers and tumor cell lines, antagonizes the ubiquitin/proteasome pathway. In the present study, we show that ISG15 is a determinant for CPT sensitivity/resistance possibly through its effect on proteasome-mediated repair of topoisomerase I (TOP1)-DNA covalent complexes. First, short hairpin RNA-mediated knockdown of either ISG15 or UbcH8 (major E2 for ISG15) in breast cancer ZR-75-1 cells decreased CPT sensitivity, suggesting that ISG15 overexpression in tumors could be a factor affecting intrinsic CPT sensitivity in tumor cells. Second, the level of ISG15 was found to be significantly reduced in several tumor cells selected for resistance to CPT, suggesting that altered ISG15 regulation could be a significant determinant for acquired CPT resistance. Parallel to reduced CPT sensitivity, short hairpin RNA-mediated knockdown of either ISG15 or UbcH8 in ZR-75-1 cells resulted in increased proteasomal degradation of CPT-induced TOP1-DNA covalent complexes. Taken together, these results suggest that ISG15, which interferes with proteasome-mediated repair of TOP1-DNA covalent complexes, is a potential tumor biomarker for CPT sensitivity.