State-level trends in the greenhouse gas emission intensity of US milk production.

The greenhouse gas emission intensity of US milk production (i.e., greenhouse gas emissions per unit of production) has varied across time and states. However, research has not examined how farm-sector trends affect the state-level emission intensity of production. We estimated fixed effects regressions with state-level panel data from 1992 through 2017 to test how US dairy farm-sector changes influenced the greenhouse gas emission intensity of production. We found that increases in per cow milk productivity reduced the enteric greenhouse gas emission intensity of milk production, while it had no statistically significant effect on the manure greenhouse gas emission intensity of production. In contrast, increases in average farm size and the number of farms reduced the manure greenhouse gas emission intensity of milk production, while they did not affect the enteric greenhouse gas emission intensity of production.

Histamine, mast cell tryptase and post-exercise hypotension in healthy and collapsed marathon runners.

PURPOSE: Heat stress exacerbates post-exercise hypotension (PEH) and cardiovascular disturbances from elevated body temperature may contribute to exertion-related incapacity. Mast cell degranulation and muscle mass are possible modifiers, though these hypotheses lack practical evidence. This study had three aims: (1) to characterise pre-post-responses in histamine and mast cell tryptase (MCT), (2) to investigate relationships between whole body muscle mass (WBMM) and changes in blood pressure post-marathon, (3) to identify any differences in incapacitated runners. METHODS: 24 recreational runners were recruited and successfully completed the 2019 Brighton Marathon (COMPLETION). WBMM was measured at baseline. A further eight participants were recruited from incapacitated runners (COLLAPSE). Histamine, MCT, blood pressure, heart rate, body temperature and echocardiographic measures were taken before and after exercise (COMPLETION) and upon incapacitation (COLLAPSE). RESULTS: In completion, MCT increased by nearly 50% from baseline (p = 0.0049), whereas histamine and body temperature did not vary (p > 0.946). Systolic (SBP), diastolic (DBP) and mean (MAP) arterial blood pressures and systemic vascular resistance (SVR) declined (p < 0.019). WBMM negatively correlated with Δ SBP (r = - 0.43, p = 0.046). For collapse versus completion, there were significant elevations in MCT (1.77 ± 0.25 µg/L vs 1.18 ± 0.43 µg/L, p = 0.001) and body temperature (39.8 ± 1.3 °C vs 36.2 ± 0.8 °C, p < 0.0001) with a non-significant rise in histamine (9.6 ± 17.9 µg/L vs 13.7 ± 33.9 µg/L, p = 0.107) and significantly lower MAP, DBP and SVR (p < 0.033). CONCLUSION: These data support the hypothesis that mast cell degranulation is a vasodilatory mechanism underlying PEH and exercise associated collapse. The magnitude of PEH is inversely proportional to the muscle mass and enhanced by concomitant body heating.

How applicable is the TNM 8 staging for human papillomavirus (HPV) related oropharyngeal squamous cell carcinoma (OPSCC) to a UK population of 106 patients? : A cohort comparison of the TNM 7 and TNM8 staging systems for HPV positive oropharyngeal cancer in a UK population.

PURPOSE: TNM8 introduced a new staging system for HPV positive oropharyngeal squamous cell carcinoma (OPSCC). This study aimed to investigate whether the changes made in TNM8 offer the perceived benefit in prognostication when compared to TNM7 in a specific patient population in the North East of England. METHODS: A retrospective cohort comparison study of all patients with HPV positive OPSCC (n = 106) through the Newcastle Head and Neck MDT between January 2012 to December 2014. Overall survival (OS) and Disease specific survival (DSS) data at 3 years was gathered for both TNM7 and TNM8. Log rank test was used to compare survival curves. Harrell's C-index adjusted for age and smoking status was used to assess prognostic ability of the two staging methods. RESULTS: TNM8 downstages disease (TNM7 stage IV patients n = 74, TNM8 stage IV patients n = 2) but gives a more even distribution of patients across disease stages. Survival for TNM8 stage II and III is similar. In our small cohort, the log-rank test detected differences in OS between stages for both scoring methods (TNM7 p = 0.006, TNM8 p < 0.001) and similarly for DSS (TNM7 p = 0.001, TNM8 p < 0.001). Harrell's C-index was similar for both models for OS (TNM7 0.71, TNM8 0.71) and DSS (TNM7 0.74, TNM8 0.70). CONCLUSION: TNM8 downstages disease and prognosticates well for stage I disease but does not differentiate between stage II and III disease when compared to TNM7. Further adaptation is required to address this to make TNM8 a more accurate prognostic tool.

Does the gene matter? Genotype-phenotype and genotype-outcome associations in congenital melanocytic naevi.

BACKGROUND: Genotype-phenotype studies can identify subgroups of patients with specific clinical features or differing outcomes, which can help shape management. OBJECTIVES: To characterize the frequency of different causative genotypes in congenital melanocytic naevi (CMN), and to investigate genotype-phenotype and genotype-outcome associations. METHODS: We conducted a large cohort study in which we undertook MC1R genotyping from blood, and high-sensitivity genotyping of NRAS and BRAF hotspots in 156 naevus biopsies from 134 patients with CMN [male 40%; multiple CMN 76%; projected adult size (PAS) > 20 cm, 59%]. RESULTS: Mosaic NRAS mutations were detected in 68%, mutually exclusive with BRAF mutations in 7%, with double wild-type in 25%. Two separate naevi were sequenced in five of seven patients with BRAF mutations, confirming clonality. Five of seven patients with BRAF mutations had a dramatic multinodular phenotype, with characteristic histology distinct from classical proliferative nodules. NRAS mutation was the commonest in all sizes of CMN, but was particularly common in naevi with PAS > 60 cm, implying more tolerance to that mutation early in embryogenesis. Facial features were less common in double wild-type patients. Importantly, the incidence of congenital neurological disease, and apparently of melanoma, was not altered by genotype; no cases of melanoma were seen in BRAF-mutant multiple CMN, however, this genotype is rare. CONCLUSIONS: CMN of all sizes are most commonly caused by mutations in NRAS. BRAF is confirmed as a much rarer cause of multiple CMN, and appears to be commonly associated with a multinodular phenotype. Genotype in this cohort was not associated with differences in incidence of neurological disease in childhood. However, genotyping should be undertaken in suspected melanoma, for guidance of treatment. What's already known about this topic? Multiple congenital melanocytic naevi (CMN) have been shown to be caused by NRAS mosaic mutations in 70-80% of cases, by BRAF mosaicism in one case report and by inference in some previous cases. There has been debate about genotypic association with different sizes of CMN, and no data on genotype-outcome. What does this study add? NRAS mosaicism was found in 68%, BRAF in 7% and double wild-type in 25% of cases of CMN. NRAS was the commonest mutation in all sizes of CMN, but was nearly universal in projected adult size > 60 cm. BRAF is often associated with a distinct multinodular clinical/histological phenotype. Adverse outcomes did not differ between genotypes on current numbers.

Long-term outcomes from prophylactic or episodic treatment of haemophilia A: A systematic review.

INTRODUCTION: Evaluating treatment success in patients with haemophilia A (HA) remains a vigorous debate, especially concerning the interpretation of results from clinical and observational research. The benefits of short-term prophylaxis are well established, but long-term outcomes, particularly related to humanistic and economic burden, are not as well understood. AIM: We conducted a systematic literature review to evaluate the association of episodic or prophylactic bleed control with long-term clinical, humanistic and economic outcomes. METHODS: Studies published in English between 1 January 2006 and 15 December 2016 were included. Participants had HA (with or without inhibitors), received prophylactic or episodic treatment and had at least 4 years of treatment or follow-up. Results were analysed qualitatively with descriptive findings. RESULTS: A total of 2091 records were screened, resulting in 19 studies from 20 publications for inclusion. Most studies included children (84%), were limited to patients with severe disease (74%) and were conducted in Europe or North America (89%). Ten studies (53%) included patients with inhibitors. Median study follow-up ranged from 5 to 19 years. Long-term bleeding and haemarthrosis outcomes were consistently better for patients receiving prophylaxis, who also required fewer hospitalizations or surgeries. Health-related quality of life, functionality and productivity were generally more favourable in patients receiving prophylaxis. Quantitative comparisons were not feasible due to the lack of consistency in endpoint collection and reporting among studies. CONCLUSION: This systematic review confirmed that the benefits of prophylactic treatment on short-term outcomes translate to broader long-term clinical, humanistic and economic benefits. Better harmonization of data collection and outcome assessments across both registries and clinical studies is needed to allow for effective comparisons across studies and across data sources.

Energy expenditure of rugby players during a 14-day in-season period, measured using doubly labelled water.

Criterion data for total energy expenditure (TEE) in elite rugby are lacking, which prediction equations may not reflect accurately. This study quantified TEE of 27 elite male rugby league (RL) and rugby union (RU) players (U16, U20, U24 age groups) during a 14-day in-season period using doubly labelled water (DLW). Measured TEE was also compared to estimated, using prediction equations. Resting metabolic rate (RMR) was measured using indirect calorimetry, and physical activity level (PAL) estimated (TEE:RMR). Differences in measured TEE were unclear by code and age (RL 4369 ± 979; RU 4365 ± 1122; U16, 4010 ± 744; U20, 4414 ± 688; U24, 4761 ± 1523 Kcal day- 1). Differences in PAL (overall mean 2.0 ± 0.4) were unclear. Very likely differences were observed in RMR by code (RL 2366 ± 296; RU 2123 ± 269 Kcal day- 1). Differences in relative RMR between U20 and U24 were very likely (U16, 27 ± 4; U20, 23 ± 3; U24, 26 ± 5 Kcal kg- 1 day- 1). Differences were observed between measured and estimated TEE, using Schofield, Cunningham and Harris-Benedict equations for U16 (187 ± 614, unclear; - 489 ± 564, likely and - 90 ± 579, unclear Kcal day- 1), U20 (- 449 ± 698, likely; - 785 ± 650, very likely and - 452 ± 684, likely Kcal day- 1) and U24 players (- 428 ± 1292; - 605 ± 1493 and - 461 ± 1314 Kcal day- 1, all unclear). Rugby players have high TEE, which should be acknowledged. Large inter-player variability in TEE was observed demonstrating heterogeneity within groups, thus published equations may not appropriately estimate TEE.

General illness and psychological factors in patients with chronic nasal symptoms.

OBJECTIVES: Only a minority of patients referred to specialists with sinonasal symptoms have clear evidence of chronic rhinosinusitis (CRS). This study aims to estimate the prevalence of and associations between (i) general illness factors (fatigue, autonomic dysfunction) and (ii) psychological factors (anxiety, depression, somatisation, personality traits) in patients presenting with sinonasal symptoms. DESIGN: The following validated questionnaires were administered to patients: the Sino-Nasal Outcome Test-22 (SNOT-22) identifying symptom burden, Composite Autonomic Symptom Score-31 (COMPASS-31) measuring autonomic function, Chalder Fatigue Questionnaire, Patient Health Questionnaire-15 (PHQ-15) addressing somatisation symptoms, Hospital Anxiety and Depression Scale (HADS), and the International Personality Item Pool-50 (IPIP-50). Comparisons were made with normative and general population data, and relationships were analysed using nonparametric correlation. SETTING: Secondary care ENT outpatients. PARTICIPANTS: Adults referred with chronic sinonasal symptoms. MAIN OUTCOME MEASURES: SNOT-22, COMPASS-31, Chalder, PHQ-15, HADS, and IPIP-50 questionnaire scores. RESULTS: Sixty-one patients were included. There was a high prevalence of all general and psychological factors assessed compared with controls. Total SNOT-22 scores showed significant correlation with Chalder fatigue scores, total autonomic dysfunction score, anxiety, depression, somatisation tendencies and the emotionally unstable personality trait. Emotional instability and psychological dysfunction correlated significantly with sleep and psychological subscales of SNOT-22 but not the rhinological or ear/facial subscales. CONCLUSION: Patients with sinonasal symptoms demonstrate high prevalence and complex associations of general illness factors, psychological distress and certain personality traits. The SNOT-22 is a valuable tool, but its utility is limited by correlations with these confounding factors (eg psychological factors) that may exaggerate the total score. The use of the SNOT-22 component subscales is likely to provide more clinically meaningful and discriminant information.

Power supplies and equipment for military field research: lessons from the British Service Dhaulagiri Research Expedition 2016.

INTRODUCTION: The British Service Dhaulagiri Research Expedition (BSDMRE) took place from 27 March to 31 May 2016. The expedition involved 129 personnel, with voluntary participation in nine different study protocols. Studies were conducted in three research camps established at 3600, 4600 and 5140 m and involved taking and storing blood samples, cardiac echocardiography and investigations involving a balance plate. Research in this remote environment requires careful planning in order to provide a robust and resilient power plan. In this paper we aim to report the rationale for the choices we made in terms of power supply, the equipment used and potential military applicability. METHODS: This is a descriptive account from the expedition members involved in planning and conducting the medical research. RESULTS: Power calculations were used to determine estimates of requirement prior to the expedition. The primary sources used to generate power were internal combustion engine (via petrol fuelled electric generators) and solar panels. Having been generated, power was stored using lithium-ion batteries. Special consideration was given to the storage of samples taken in the field, for which electric freezers and dry shippers were used. All equipment used functioned well during the expedition, with the challenges of altitude, temperature and transport all overcome due to extensive prior planning. CONCLUSIONS: Power was successfully generated, stored and delivered during the BSDMRE, allowing extensive medical research to be undertaken. The challenges faced and overcome are directly applicable to delivering military medical care in austere environments, and lessons learnt can help with the planning and delivery of future operations, training exercises or expeditions.

Haemophilia care in Europe - A survey of 37 countries.

INTRODUCTION: The European Haemophilia Consortium (EHC) is an international non-profit organization representing 45 national patients' organizations in Europe. Every 3 years, the EHC circulates a survey to its national member organizations to assess the state of haemophilia care. AIM: The purpose of this exercise is to ascertain information about the organization of haemophilia care and treatment availability at national levels. Furthermore, the survey provides a basis from which the EHC are able to monitor the unmet need and stability of care/treatment access in the individual member countries. PATIENTS AND METHODS: Surveys are distributed to EHC member organizations in English and Russian. Patient organizations are encouraged to share the survey with local clinicians to ensure accuracy of responses. The data collected are in part consistent to provide a longitudinal overview for treatment access, but topical items are included such as ageing. Subsequently, completed surveys are transposed into a database for analysis and reporting. RESULTS: Thirty-seven responses were received from the 45 countries approached, representing an 82% response rate from members. Findings suggest increased access to treatment and some improvement in certain areas of care. However, access to treatment has declined or remained largely unchanged in some countries. CONCLUSION: The survey has been a successful exercise in enabling a greater understanding of the current Haemophilia care landscape across Europe. However, there remain unmet needs in various aspects of patient care, and specific examples include psychosocial care and general preparedness for an ageing haemophilia population.

Baseline swallowing measures predict recovery at 6 weeks after transoral robotic surgery for head and neck cancer.

OBJECTIVES: To explore whether pre-treatment swallowing measures predict swallowing recovery at 6 weeks after transoral robotic surgery (TORS). DESIGN: Prospective cohort study. SETTING: Tertiary care cancer centre in the United Kingdom. PARTICIPANTS: Fifty-one consecutive patients undergoing TORS for head and neck cancer, between April 2013 and February 2015. MAIN OUTCOME MEASURES: Swallowing function assessed by Performance Status Scale (PSS) Normalcy of Diet, timed water swallow test capacity scores (WST) and duration of tube feeding. RESULTS: The primary site distribution was as follows: 21 oropharynx, 8 larynx, 6 mucosectomy and 6 hypopharynx. T stages included 7 staged Tx, 21 T1-T2 tumours and 1 T3 tumour. Moderate-to-severe comorbidity was found in 45/51 patients. Mean PSS score was 83 (sd 27.54); mean WST score was 11.14 (sd 7.97). Most patients (73%) required tube feeding post-operatively, with mean tube feed duration of 18.08 days (sd 17.91); 76% resumed oral intake by 6 weeks. Pre-treatment swallow tests showed moderate negative correlation with tube feeding duration: PSS (rho 0-.430, P = .003); WST (rho 0-.503, P = 0.002). CONCLUSIONS: The majority of TORS patients resume oral intake by 6 weeks. This study shows that impaired swallowing prior to surgery correlates with post-operative duration of tube feeding and strengthens the evidence for the utility of these measures in this clinical setting.

'Thinking that somebody's going to delay [a tonsillectomy] for one to two years is quite horrifying really': a qualitative feasibility study for the NAtional Trial of Tonsillectomy IN Adults (NATTINA Part 2).

OBJECTIVES: Level one evidence on the value of adult tonsillectomy versus non-surgical management remains scarce. Before embarking on a costly national randomised controlled trial, it is essential to establish its feasibility. DESIGN: Feasibility study with in-depth qualitative and cognitive interviews. SETTING: ENT staff and patients were recruited from nine hospital centres across England and Scotland. PARTICIPANTS: Patients who were referred for tonsillectomy (n = 15), a convenience sample of general practitioners (n = 11) and ear, nose and throat staff (n = 22). MAIN OUTCOME MEASURES: To ascertain whether ear, nose and throat staff would be willing to randomise patients to the treatment arms. To assess general practitioners' willingness to refer patients to the NAtional Trial of Tonsillectomy IN Adults (NATTINA) centres. To assess patients' willingness to be randomised and the acceptability of the deferred surgery treatment arm. To ascertain whether the study could progress to the pilot trial stage. RESULTS: Ear, nose and throat staff and general practitioners were willing to randomise patients to the proposed NATTINA. Not all ENT staff were in equipoise concerning the treatment pathways. Patients were reluctant to be randomised into the deferred surgery group if they had already waited a substantial time before being referred. CONCLUSIONS: Findings suggest that the NATTINA may not be feasible. Proposed methods could not be realistically assessed without a pilot trial. Due to the importance of the question, as evidenced by NATTINA clinicians, and strong support from ENT staff, the pilot trial proceeded, with modifications.

Trans-oral robotic assisted tongue base mucosectomy for investigation of cancer of unknown primary in the head and neck region. The UK experience.

OBJECTIVES: The diagnosis of cancer of unknown primary (CUP) in head and neck occurs when the treating clinicians have utilised all available diagnostic tests and failed to identify the origin of the disease. There is no agreed consensus on which diagnostic investigations to use, or the order in which to use them in, although broad recommendations exist. Small tumours arising in the tongue base can be below the limits of resolution of conventional diagnostic techniques. Given the difficulty in targeting the tongue base, current practice involves blind random biopsies, which leads to a variable detection rate. Robotically assisted surgical removal of the tongue base, tongue base mucosectomy (TBM) has been shown to improve diagnostic yield. This study reports the diagnostic hit rate for tongue base primaries using this technique. DESIGN: Retrospective case review. SETTING: UK Head and Neck Centres. PARTICIPANTS: Patients presenting as an unknown primary, investigated with clinical examination, PET-CT and palatine tonsillectomy. MAIN OUTCOME MEASURES: The detection of a primary site of head and neck cancer in the otherwise unknown primary tumour. RESULTS: The primary tumour site was identified in the tongue base in 53% (n=17) of patients. In 15 patients the tumour was in the ipsliateral tongue base (88%) while in two cases (12%) the tumour was located in contra lateral tongue base. CONCLUSIONS: Trans-oral robotic assisted TBM raises the possibility of identifying over 50% of tumours that would otherwise be classified as CUP. Identifying these in the contralateral tongue base has implications for treatment planning and outcome.

The British Services Dhaulagiri Medical Research Expedition 2016: a unique military and civilian research collaboration.

INTRODUCTION: High-altitude environments lead to a significant physiological challenge and disease processes which can be life threatening; operational effectiveness at high altitude can be severely compromised. The UK military research is investigating ways of mitigating the physiological effects of high altitude. METHODS: The British Service Dhaulagiri Research Expedition took place from March to May 2016, and the military personnel were invited to consent to a variety of study protocols investigating adaptation to high altitudes and diagnosis of high-altitude illness. The studies took place in remote and austere environments at altitudes of up to 7500 m. RESULTS: This paper gives an overview of the individual research protocols investigated, the execution of the expedition and the challenges involved. 129 servicemen and women were involved at altitudes of up to 7500 m; 8 research protocols were investigated. CONCLUSIONS: The outputs from these studies will help to individualise the acclimatisation process and inform strategies for pre-acclimatisation should troops ever need to deploy at high altitude at short notice.

The Reliability of a Pre-Loaded Treadmill Time-Trial in Moderate Normobaric Hypoxia.

The purpose of this study was to assess the reliability of a pre-loaded 1 500-m treadmill time trial, conducted in moderate normobaric hypoxia. 8 trained runners/triathletes (24±3 years, 73.2±8.1 kg, 182.5±6.5 cm, altitude specific V˙O2max: 52.9±5.5 ml·kg(-1)·min(-1)) completed 3 trials (the first as a familiarisation), involving 2, 15-min running bouts at 45% and 65% V˙O2max, respectively, and a 1 500-m time trial in moderate normobaric hypoxia equivalent to a simulated altitude of 2 500 m (FiO2~15%). Heart rate, arterial oxygen saturation, skeletal muscle and cerebral tissue oxygenation (StO2), expired gas ( V˙O2 and V˙CO2), and ratings of perceived exertion were monitored. Running performance (Trial 1: 352.7±40; Trial 2: 353.9±38.2 s) demonstrated a low CV (0.9%) and high ICC (1). All physiological variables demonstrated a global CV≤4.2%, and ICC≥0.87, with the exception of muscle (CV 10.4%; ICC 0.70) and cerebral (CV 4.1%; ICC 0.82) StO2. These data demonstrate good reliability of the majority of physiological variables and indicate that a pre-loaded 1 500-m time trial conducted in moderate normobaric hypoxia is a highly reliable test of performance.

Functional swallowing outcomes following treatment for oropharyngeal carcinoma: a systematic review of the evidence comparing trans-oral surgery versus non-surgical management.

BACKGROUND: Trans-oral surgical and non-surgical management options for oropharyngeal squamous cell carcinoma (OPSCC) appear to offer similar survival outcomes. Functional outcomes, in particular swallowing, have become of increasing interest in the debate regarding treatment options. Contemporary reviews on function following treatment frequently include surrogate markers and limit the value of comparative analysis. OBJECTIVES OF REVIEW: A systematic review was performed to establish whether direct comparisons of swallowing outcomes could be made between trans-oral surgical approaches (trans-oral laser microsurgery (TLM)/trans-oral robotic surgery (TORS)) and (chemo)radiotherapy ((C)RT). TYPE OF REVIEW: Systematic review. SEARCH STRATEGY: MEDLINE, Embase and Cochrane databases were interrogated using the following MeSH terms: antineoplastic protocols, chemotherapy, radiotherapy, deglutition disorders, swallowing, lasers, and trans-oral surgery. EVALUATION METHOD: Two authors performed independent systematic reviews and consensus was sought if opinions differed. The WHO ICF classification was applied to generate analysis based around body functions and structure, activity limitations and participation restriction. RESULTS: Thirty-seven citations were included in the analysis. Twenty-six papers reported the outcomes for OPSCC treatment following primary (C)RT in 1377 patients, and 15 papers following contemporary trans-oral approaches in 768 patients. Meta-analysis was not feasible due to varying methodology and heterogeneity of outcome measures. Instrumental swallowing assessments were presented in 13/26 (C)RT versus 2/15 TLM/TORS papers. However, reporting methods of these studies were not standardised. This variety of outcome measures and the wide-ranging intentions of authors applying the measures in individual studies limit any practical direct comparisons of the effects of treatment on swallowing outcomes between interventions. CONCLUSIONS: From the current evidence, no direct comparisons could be made of swallowing outcomes between the surgical and non-surgical modalities. Swallowing is a multidimensional construct, and the range of assessments utilised by authors reflects the variety of available reporting methods. The MD Anderson Dysphagia Inventory is a subjective measure that allows limited comparison between the currently available heterogeneous data, and is explored in detail. The findings highlight that further research may identify the most appropriate tools for measuring swallowing in patients with OPSCC. Consensus should allow their standardised integration into future studies and randomised control trials.

One-year swallowing outcomes following transoral laser microsurgery +/- adjuvant therapy versus primary chemoradiotherapy for advanced stage oropharyngeal squamous cell carcinoma.

OBJECTIVES: To assess the between-group change in swallowing function from baseline to 12 months following treatment, for patients treated for resectable stage III and IVA oropharyngeal squamous cell carcinoma. To assess the within-group change in swallowing function between 3 and 12 months following treatment. DESIGN: Non-randomised cohort study. SETTING: A single head and neck cancer unit with oncology services held at the nearby regional treatment centre. PARTICIPANTS: Twenty-five patients treated with Transoral Laser Microsurgery +/- adjuvant (chemo)radiotherapy (Transoral Laser Microsurgery) observed alongside an historic cohort of 33 patients treated with (chemo)radiotherapy. MAIN OUTCOME MEASURES: The patient reported MD Anderson Dysphagia Inventory (MDADI), an objective timed Water Swallow Test, and the clinician rated normalcy of diet subsection of the Performance of Swallowing Scale . RESULTS: Between baseline and 12 months, patients treated with primary (chemo)radiotherapy demonstrated greater deterioration in swallowing function compared to Transoral Laser Microsurgery for all 3 swallowing measures. Between 3 and 12 months, the only significant change was an improvement in Performance of Swallowing Scale scores in the (chemo)radiotherapy group. CONCLUSIONS: This is the first study to report the results of a complimentary set of swallowing measures for patients treated with Transoral Laser Microsurgery, observed alongside a cohort of (chemo)radiotherapy patients. The preliminary results suggest a benefit in swallowing function for Transoral Laser Microsurgery over (chemo)radiotherapy during the year following treatment.

Dysgammaglobulinemia Associated With Glu349del, a Hypomorphic XIAP Mutation.

BACKGROUND: X-linked lymphoproliferative syndrome type 2 is a rare hereditary immunodeficiency caused by mutations in the XIAP gene. This immunodeficiency frequently results in hemophagocytic lymphohistiocytosis, although hypogammaglobulinemia and dysgammaglobulinemia are also common. OBJECTIVE: We identified 17 patients from 12 Japanese families with mutations in XIAP. The Glu349del mutation was observed in 3 patients, each from a different family. Interestingly, these patients exhibited dysgammaglobulinemia but not hemophagocytic lymphohistiocytosis. We conducted an immunological study of patients carrying Glu349del and other mutations to elucidate the pathogenic mechanisms of dysgammaglobulinemia in patients with mutations in the XIAP gene. PATIENTS AND METHODS: We performed an immunological study of 2 patients carrying the Glu349del mutation and 8 patients with other mutations. RESULTS: Flow cytometry showed that the percentage of memory B cells in patients with a mutation in XIAP was lower than that observed in the healthy controls. The patients with the Glu349del mutation had a lower percentage of memory B cells than those with other mutations. Ig production was reduced in patients with the Glu349del mutation. Increased susceptibility to apoptosis was observed in the patients with other mutations. Susceptibility to apoptosis was normal in patients with Glu349del. Microarray analysis indicated that expression of Ig-related genes was reduced in patients with the Glu349del mutation and that the pattern was different from that observed in the healthy controls or patients with other mutations in XIAP. CONCLUSIONS: Patients carrying the Glu349del mutation in the XIAP gene may have a clinically and immunologically distinct phenotype from patients with other XIAP mutations. The Glu349del mutation may be associated with dysgammaglobulinemia.

Considering maturation status and relative age in the longitudinal evaluation of junior rugby league players.

This study longitudinally evaluated whether maturation and relative age interact with time during adolescence to differentially affect the development of anthropometric and fitness characteristics in junior rugby league players. Anthropometric and fitness characteristics of 81 junior players selected into the UK Rugby Football League's talent identification and development process were assessed over three consecutive occasions (i.e., under-13s, -14s, -15s). Players were grouped and compared in relation to maturational status (i.e., early, average, late) and relative age quartile (i.e., quartile 1). Repeated measures multivariate analysis of variance identified significant (P < 0.001) overall main effects for maturation group, relative age quartile and importantly a maturation group by time interaction. Findings showed that the early-maturing group had the greatest anthropometric characteristics and medicine ball throw across the three occasions. However, the late-maturing group increased their height (early = 5.0 cm, late = 10.3 cm), medicine ball throw and 60-m sprint (early = -0.46 s, late = -0.85 s) the most throughout the 2-year period. Early (de)selection policies currently applied in talent identification and development programs are questionable when performance-related variables are tracked longitudinally. During adolescence, maturation status alongside relative age should be considered and controlled for when assessing athlete potential for future progression.