Regional and time course differences in sweat cortisol, glucose, and select cytokine concentrations during exercise.

INTRODUCTION: The use of sweat as a biofluid for non-invasive sampling and diagnostics is a popular area of research. However, concentrations of cortisol, glucose, and cytokines have not been described across anatomical regions or as time progresses throughout exercise. PURPOSE: To determine regional and time course differences in sweat cortisol, glucose, and select cytokines (EGF, IFN-γ, IL-1ß, IL-1α, IL-1ra, TNF-α, IL-6, IL-8, and IL-10). METHODS: Sweat was collected with absorbent patches from eight subjects (24-44 y; 80.2 ± 10.2 kg) on the forehead (FH), right dorsal forearm (RDF), right scapula (RS), and right triceps (RT) at 0-25 min, 30-55 min, and 60-85 min during 90 min of cycling (~ 82% HRmax) in a heated chamber (32 °C, 50% rh). ANOVA was used to determine the effect of site and time on outcomes. Data are reported as LS means ± SE. RESULTS: There was a significant effect of location on sweat analyte concentrations with FH having higher values than most other regions for cortisol (FH: 1.15 ± 0.08 ng/mL > RDF: 0.62 ± 0.09 ng/mL and RT: 0.65 ± 0.12 ng/mL, P = 0.02), IL-1ra (P < 0.0001), and IL-8 (P < 0.0001), but lower concentrations for glucose (P = 0.01), IL-1α (P < 0.0001), and IL-10 (P = 0.02). Sweat IL-1ß concentration was higher on the RS than RT (P < 0.0001). Sweat cortisol concentration increased (25 min: 0.34 ± 0.10 ng/mL < 55 min: 0.89 ± 0.07 ng/mL < 85 min: 1.27 ± 0.07 ng/mL; P < 0.0001), while EGF (P < 0.0001), IL-1ra (P < 0.0001), and IL-6 (P = 0.02) concentrations decreased over time. CONCLUSION: Sweat analyte concentrations varied with time of sampling and anatomical region, which is essential information to consider when conducting future work in this area. CLINICAL TRIAL IDENTIFIER: NCT04240951 registered January 27, 2020.

Co-designing a peer-led model of delivering behavioural activation for people living with depression or low mood in Australian farming communities.

INTRODUCTION: Farmers face a range of factors that negatively influence their mental health and suicide risk, yet have limited access to appropriate support. Behavioural activation (BA) is an evidence-based therapy that can be effectively delivered by nonclinical workers. Working with members of farming communities to deliver BA to their peers has the potential to overcome many well-established barriers to mental health help-seeking and improve outcomes for this at-risk group. OBJECTIVE: This paper describes the findings of a co-design phase informing the development of a peer (farmer)-led approach for delivering BA for farmers living with depression or low mood. DESIGN: This qualitative study used a co-design approach involving members of the target community. Focus groups were transcribed and analysed using Thematic Analysis and the Framework approach. FINDINGS: Ten online focus groups with 22 participants were held over 3 months. Four overarching, interlinked themes were identified: (i) filling the gap in rural mental health support; (ii) alignment with the farming context-tailoring how, where and when we engage about mental health; (iii) the 'messenger' is as important as the message; and (iv) sustainability, governance and support. DISCUSSION: Findings suggest BA could be a contextually appropriate model of support for the farming community-given its practical and solution-focused approach-and could help improve access to support. Having peer workers deliver the intervention was viewed as appropriate. Ensuring governance structures are developed to support peers to deliver the intervention will be essential to facilitate effectiveness, safety and sustainability. CONCLUSION: Insights gained through co-design have been critical to the success of developing this new model of support for members of farming communities experiencing depression or low mood.

Participant perspectives of an online co-design process to develop a prevention-focused mental health and well-being platform for primary producers.

OBJECTIVE: To explore participant experiences of an online co-design process to develop a web-based preventative mental health and well-being intervention targeting primary producers in rural Australia. SETTING: Rural Victoria, Australia. PARTICIPANTS: Participants from a primary producer background, including horticulture, fisheries, animal cultivation and farm consultancy, were eligible for the study if they had participated in both the co-design and beta testing processes for a primary producer platform. DESIGN: A qualitative study using semi-structured phone-based interviews was undertaken. A reflexive inductive approach to data analysis was employed to develop themes. RESULTS: Eleven participants were interviewed, with an average age of 51 years, of which 7 were female. Five main themes were developed. These included: (1) participant diversity, (2) impact of online delivery on co-design participation, (3) experiences of the co-design process, (4) maintaining a shared vision and goals and (5) acting on the co-design recommendations. Use of online methods was a clear enabler to engage participants who were geographically dispersed and offers an alternative to more conventional approaches to co-design using face-to-face methods. Some aspects of participant engagement may need a greater focus when conducted online compared with face-to-face. CONCLUSIONS: Using an online co-design method to develop a preventative mental health and well-being web-based platform for primary producers was novel. Findings address a gap in the literature around the experience of participants engaging in a co-design process and identify opportunities to improve participant engagement and experience with the online format.

Auditory and tactile frequency representations are co-embedded in modality-defined cortical sensory systems.

Sensory information is represented and elaborated in hierarchical cortical systems that are thought to be dedicated to individual sensory modalities. This traditional view of sensory cortex organization has been challenged by recent evidence of multimodal responses in primary and association sensory areas. Although it is indisputable that sensory areas respond to multiple modalities, it remains unclear whether these multimodal responses reflect selective information processing for particular stimulus features. Here, we used fMRI adaptation to identify brain regions that are sensitive to the temporal frequency information contained in auditory, tactile, and audiotactile stimulus sequences. A number of brain regions distributed over the parietal and temporal lobes exhibited frequency-selective temporal response modulation for both auditory and tactile stimulus events, as indexed by repetition suppression effects. A smaller set of regions responded to crossmodal adaptation sequences in a frequency-dependent manner. Despite an extensive overlap of multimodal frequency-selective responses across the parietal and temporal lobes, representational similarity analysis revealed a cortical "regional landscape" that clearly reflected distinct somatosensory and auditory processing systems that converged on modality-invariant areas. These structured relationships between brain regions were also evident in spontaneous signal fluctuation patterns measured at rest. Our results reveal that multimodal processing in human cortex can be feature-specific and that multimodal frequency representations are embedded in the intrinsically hierarchical organization of cortical sensory systems.

Auditory Frequency Representations in Human Somatosensory Cortex.

Recent studies have challenged the traditional notion of modality-dedicated cortical systems by showing that audition and touch evoke responses in the same sensory brain regions. While much of this work has focused on somatosensory responses in auditory regions, fewer studies have investigated sound responses and representations in somatosensory regions. In this functional magnetic resonance imaging (fMRI) study, we measured BOLD signal changes in participants performing an auditory frequency discrimination task and characterized activation patterns related to stimulus frequency using both univariate and multivariate analysis approaches. Outside of bilateral temporal lobe regions, we observed robust and frequency-specific responses to auditory stimulation in classically defined somatosensory areas. Moreover, using representational similarity analysis to define the relationships between multi-voxel activation patterns for all sound pairs, we found clear similarity patterns for auditory responses in the parietal lobe that correlated significantly with perceptual similarity judgments. Our results demonstrate that auditory frequency representations can be distributed over brain regions traditionally considered to be dedicated to somatosensation. The broad distribution of auditory and tactile responses over parietal and temporal regions reveals a number of candidate brain areas that could support general temporal frequency processing and mediate the extensive and robust perceptual interactions between audition and touch.

Exercise intensity effects on total sweat electrolyte losses and regional vs. whole-body sweat [Na+], [Cl-], and [K+].

PURPOSE: To quantify total sweat electrolyte losses at two relative exercise intensities and determine the effect of workload on the relation between regional (REG) and whole body (WB) sweat electrolyte concentrations. METHODS: Eleven recreational athletes (7 men, 4 women; 71.5 ± 8.4 kg) completed two randomized trials cycling (30 °C, 44% rh) for 90 min at 45% (LOW) and 65% (MOD) of VO2max in a plastic isolation chamber to determine WB sweat [Na+] and [Cl-] using the washdown technique. REG sweat [Na+] and [Cl-] were measured at 11 REG sites using absorbent patches. Total sweat electrolyte losses were the product of WB sweat loss (WBSL) and WB sweat electrolyte concentrations. RESULTS: WBSL (0.86 ± 0.15 vs. 1.27 ± 0.24 L), WB sweat [Na+] (32.6 ± 14.3 vs. 52.7 ± 14.6 mmol/L), WB sweat [Cl-] (29.8 ± 13.6 vs. 52.5 ± 15.6 mmol/L), total sweat Na+ loss (659 ± 340 vs. 1565 ± 590 mg), and total sweat Cl- loss (931 ± 494 vs. 2378 ± 853 mg) increased significantly (p < 0.05) from LOW to MOD. REG sweat [Na+] and [Cl-] increased from LOW to MOD at all sites except thigh and calf. Intensity had a significant effect on the regression model predicting WB from REG at the ventral wrist, lower back, thigh, and calf for sweat [Na+] and [Cl-]. CONCLUSION: Total sweat Na+ and Cl- losses increased by ~ 150% with increased exercise intensity. Regression equations can be used to predict WB sweat [Na+] and [Cl-] from some REG sites (e.g., dorsal forearm) irrespective of intensity (between 45 and 65% VO2max), but other sites (especially ventral wrist, lower back, thigh, and calf) require separate prediction equations accounting for workload.

Normative data for sweating rate, sweat sodium concentration, and sweat sodium loss in athletes: An update and analysis by sport.

The purpose of this study was to expand our previously published sweat normative data/analysis (n = 506) to establish sport-specific normative data for whole-body sweating rate (WBSR), sweat [Na+], and rate of sweat Na+ loss (RSSL). Data from 1303 athletes were compiled from observational testing (2000-2017) using a standardized absorbent sweat patch technique to determine local sweat [Na+] and normalized to whole-body sweat [Na+]. WBSR was determined from change in exercise body mass, corrected for food/fluid intake and urine/stool loss. RSSL was the product of sweat [Na+] and WBSR. There were significant differences between sports for WBSR, with highest losses in American football (1.51 ± 0.70 L/h), then endurance (1.28 ± 0.57 L/h), followed by basketball (0.95 ± 0.42 L/h), soccer (0.94 ± 0.38 L/h) and baseball (0.83 ± 0.34 L/h). For RSSL, American football (55.9 ± 36.8 mmol/h) and endurance (51.7 ± 27.8 mmol/h) were greater than soccer (34.6 ± 19.2 mmol/h), basketball (34.5 ± 21.2 mmol/h), and baseball (27.2 ± 14.7 mmol/h). After ANCOVA, significant between-sport differences in adjusted means for WBSR and RSSL remained. In summary, due to the significant sport-specific variation in WBSR and RSSL, American football and endurance have the greatest need for deliberate hydration strategies. Abbreviations: WBSR: whole body sweating rate; SR: sweating rate; Na+: sodium; RSSL: rate of sweat sodium loss.

Resting-state functional connectivity predicts longitudinal change in autistic traits and adaptive functioning in autism.

Although typically identified in early childhood, the social communication symptoms and adaptive behavior deficits that are characteristic of autism spectrum disorder (ASD) persist throughout the lifespan. Despite this persistence, even individuals without cooccurring intellectual disability show substantial heterogeneity in outcomes. Previous studies have found various behavioral assessments [such as intelligence quotient (IQ), early language ability, and baseline autistic traits and adaptive behavior scores] to be predictive of outcome, but most of the variance in functioning remains unexplained by such factors. In this study, we investigated to what extent functional brain connectivity measures obtained from resting-state functional connectivity MRI (rs-fcMRI) could predict the variance left unexplained by age and behavior (follow-up latency and baseline autistic traits and adaptive behavior scores) in two measures of outcome--adaptive behaviors and autistic traits at least 1 y postscan (mean follow-up latency = 2 y, 10 mo). We found that connectivity involving the so-called salience network (SN), default-mode network (DMN), and frontoparietal task control network (FPTCN) was highly predictive of future autistic traits and the change in autistic traits and adaptive behavior over the same time period. Furthermore, functional connectivity involving the SN, which is predominantly composed of the anterior insula and the dorsal anterior cingulate, predicted reliable improvement in adaptive behaviors with 100% sensitivity and 70.59% precision. From rs-fcMRI data, our study successfully predicted heterogeneity in outcomes for individuals with ASD that was unaccounted for by simple behavioral metrics and provides unique evidence for networks underlying long-term symptom abatement.

Sweat Sodium, Potassium, and Chloride Concentrations Analyzed Same Day as Collection Versus After 7 Days Storage in a Range of Temperatures.

The purpose of this study was to determine the effect of storage temperature on sodium ([Na+]), potassium ([K+]), and chloride ([Cl-]) concentrations of sweat samples analyzed 7 days after collection. Using the absorbent patch technique, 845 sweat samples were collected from 39 subjects (32 ± 7 years, 72.9 ± 10.5 kg) during exercise. On the same day as collection (PRESTORAGE), 609 samples were analyzed for [Na+], [Cl-], and [K+] by ion chromatography (IC) and 236 samples were analyzed for [Na+] using a compact ion-selective electrode (ISE). Samples were stored at one of the four conditions: -20 °C (IC, n = 138; ISE, n = 60), 8 °C (IC, n = 144; ISE, n = 59), 23 °C (IC, n = 159; ISE, n = 59), or alternating between 8 °C and 23 °C (IC, n = 168; ISE, n = 58). After 7 days in storage (POSTSTORAGE), samples were reanalyzed using the same technique as PRESTORAGE. PRESTORAGE sweat electrolyte concentrations were highly related to that of POSTSTORAGE (intraclass correlation coefficient: .945-.989, p < .001). Mean differences (95% confidence intervals) between PRESTORAGE and POSTSTORAGE were statistically, but not practically, significant for most comparisons: IC [Na+]: -0.5(0.9) to -2.1(0.9) mmol/L; IC [K+]: -0.1(0.1) to -0.2(0.1) mmol/L; IC [Cl-]: -0.4(1.4) to -1.3(1.3) mmol/L; ISE [Na+]: -2.0(1.1) to 1.3(1.1) mmol/L. Based on typical error of measurement results, 95% of the time PRESTORAGE and POSTSTORAGE sweat [Na+], [K+], and [Cl-] by IC analysis fell within ±7-9, ±0.6-0.7, and ±9-13 mmol/L, respectively, while sweat [Na+] by ISE was ±6 mmol/L. All conditions produced high reliability and acceptable levels of agreement in electrolyte concentrations of sweat samples analyzed on the day of collection versus after 7 days in storage.

Normative data for regional sweat sodium concentration and whole-body sweating rate in athletes.

The purpose of this study was to establish normative data for regional sweat sodium concentration ([Na+]) and whole-body sweating rate in athletes. Data from 506 athletes (367 adults, 139 youth; 404 male, 102 female) were compiled from observational athlete testing for a retrospective analysis. The participants were skill/team-sport (including American football, baseball, basketball, soccer and tennis) and endurance (including cycling, running and triathlon) athletes exercising in cool to hot environmental conditions (15-50 °C) during training or competition in the laboratory or field. A standardised regional absorbent patch technique was used to determine sweat [Na+] on the dorsal mid-forearm. Whole-body sweat [Na+] was predicted using a published regression equation (y = 0.57x+11.05). Whole-body sweating rate was calculated from pre- to post-exercise change in body mass, corrected for fluid/food intake (ad libitum) and urine output. Data are expressed as mean ± SD (range). Forearm sweat [Na+] and predicted whole-body sweat [Na+] were 43.6 ± 18.2 (12.6-104.8) mmol · L(-1) and 35.9 ± 10.4 (18.2-70.8) mmol · L(-1), respectively. Absolute and relative whole-body sweating rates were 1.21 ± 0.68 (0.26-5.73) L · h(-1) and 15.3 ± 6.8 (3.3-69.7) ml · kg(-1) · h(-1), respectively. This retrospective analysis provides normative data for athletes' forearm and predicted whole-body sweat [Na+] as well as absolute and relative whole-body sweating rate across a range of sports and environmental conditions.

Non-invasive estimation of hydration status changes through tear fluid osmolarity during exercise and post-exercise rehydration.

PURPOSE: To determine if tear fluid osmolarity (Tosm) can track changes in hydration status during exercise and post-exercise rehydration. METHODS: Nineteen male athletes (18-37 years, 74.6 ± 7.9 kg) completed two randomized, counterbalanced trials; cycling (~95 min) with water intake to replace fluid losses or water restriction to progressively dehydrate to 3 % body mass loss (BML). After exercise, subjects drank water to maintain body mass (water intake trials) or progressively rehydrate to pre-exercise body mass (water restriction trials) over a 90-min recovery period. Plasma osmolality (Posm) and Tosm measurements (mean of right and left eyes) were taken pre-exercise, during rest periods between exercise bouts corresponding to 1, 2, and 3 % BML, and rehydration at 2, 1, and 0 % BML. RESULTS: During exercise mean (± SD) Tosm was significantly higher in water restriction vs. water intake trials at 1 % BML (299 ± 9 vs. 293 ± 9 mmol/L), 2 % BML (301 ± 9 vs. 294 ± 9 mmol/L), and 3 % BML (302 ± 9 vs. 292 ± 8 mmol/L). Mean Tosm progressively decreased during post-exercise rehydration and was not different between trials at 1 % BML (291 ± 8 vs. 290 ± 7 mmol/L) and 0 % BML (288 ± 7 vs. 289 ± 8 mmol/L). Mean Tosm tracked changes in hydration status similar to that of mean Posm; however, the individual responses in Tosm to water restriction and water intake was considerably more variable than that of Posm. CONCLUSION: Tosm is a valid indicator of changes in hydration status when looking at the group mean; however, large differences among subjects in the Tosm response to hydration changes limit its validity for individual recommendations.

Individual differences in intrinsic brain connectivity predict decision strategy.

When humans are provided with ample time to make a decision, individual differences in strategy emerge. Using an adaptation of a well-studied decision making paradigm, motion direction discrimination, we probed the neural basis of individual differences in strategy. We tested whether strategies emerged from moment-to-moment reconfiguration of functional brain networks involved in decision making with task-evoked functional MRI (fMRI) and whether intrinsic properties of functional brain networks, measured at rest with functional connectivity MRI (fcMRI), were associated with strategy use. We found that human participants reliably selected one of two strategies across 2 days of task performance, either continuously accumulating evidence or waiting for task difficulty to decrease. Individual differences in decision strategy were predicted both by the degree of task-evoked activation of decision-related brain regions and by the strength of pretask correlated spontaneous brain activity. These results suggest that spontaneous brain activity constrains strategy selection on perceptual decisions.

Mutational loss of PTEN induces resistance to NOTCH1 inhibition in T-cell leukemia.

Gain-of-function mutations in NOTCH1 are common in T-cell lymphoblastic leukemias and lymphomas (T-ALL), making this receptor a promising target for drugs such as gamma-secretase inhibitors, which block a proteolytic cleavage required for NOTCH1 activation. However, the enthusiasm for these therapies has been tempered by tumor resistance and the paucity of information on the oncogenic programs regulated by oncogenic NOTCH1. Here we show that NOTCH1 regulates the expression of PTEN (encoding phosphatase and tensin homolog) and the activity of the phosphoinositol-3 kinase (PI3K)-AKT signaling pathway in normal and leukemic T cells. Notch signaling and the PI3K-AKT pathway synergize in vivo in a Drosophila melanogaster model of Notch-induced tumorigenesis, and mutational loss of PTEN is associated with human T-ALL resistance to pharmacological inhibition of NOTCH1. Overall, these findings identify transcriptional control of PTEN and regulation of the PI3K-AKT pathway as key elements of the leukemogenic program activated by NOTCH1 and provide the basis for the design of new therapeutic strategies for T-ALL.

Parcellation in left lateral parietal cortex is similar in adults and children.

A key question in developmental neuroscience involves understanding how and when the cerebral cortex is partitioned into distinct functional areas. The present study used functional connectivity MRI mapping and graph theory to identify putative cortical areas and generate a parcellation scheme of left lateral parietal cortex (LLPC) in 7 to 10-year-old children and adults. Results indicated that a majority of putative LLPC areas could be matched across groups (mean distance between matched areas across age: 3.15 mm). Furthermore, the boundaries of children's putative LLPC areas respected the boundaries generated from the adults' parcellation scheme for a majority of children's areas (13/15). Consistent with prior research, matched LLPC areas showed age-related differences in functional connectivity strength with other brain regions. These results suggest that LLPC cortical parcellation and functional connectivity mature along different developmental trajectories, with adult-like boundaries between LLPC areas established in school-age children prior to adult-like functional connectivity.

Functional neuroimaging study in identical twin pairs discordant for regular cigarette smoking.

Despite the tremendous public health and financial burden of cigarette smoking, relatively little is understood about brain mechanisms that subserve smoking behavior. This study investigated the effect of lifetime regular smoking on brain processing in a reward guessing task using functional magnetic resonance imaging and a co-twin control study design in monozygotic (MZ) twin pairs that maximally controls for genetic and family background factors. Young adult (24-34 years) MZ female twin pairs (n = 15 pairs), discordant for regular smoking defined using Centers for Disease Control criteria as having smoked ≥100 cigarettes in their lifetime, were recruited from an ongoing genetic epidemiological longitudinal study of substance use and psychopathology. We applied hypothesis-driven region of interest (ROI) and whole-brain analyses to investigate the effect of regular smoking on reward processing. Reduced response to reward and punishment in regular compared with never-regular smokers was seen in hypothesis-driven ROI analysis of bilateral ventral striatum. Whole-brain analysis identified bilateral reward-processing regions that showed activation differences in response to winning or losing money but no effect of regular smoking; and frontal/parietal regions, predominantly in the right hemisphere, that showed robust effect of regular smoking but no effect of winning or losing money. Altogether, using a study design that maximally controls for group differences, we found that regular smoking had modest effects on striatal reward processing regions but robust effects on cognitive control/attentional systems.

Spurious but systematic correlations in functional connectivity MRI networks arise from subject motion.

Here, we demonstrate that subject motion produces substantial changes in the timecourses of resting state functional connectivity MRI (rs-fcMRI) data despite compensatory spatial registration and regression of motion estimates from the data. These changes cause systematic but spurious correlation structures throughout the brain. Specifically, many long-distance correlations are decreased by subject motion, whereas many short-distance correlations are increased. These changes in rs-fcMRI correlations do not arise from, nor are they adequately countered by, some common functional connectivity processing steps. Two indices of data quality are proposed, and a simple method to reduce motion-related effects in rs-fcMRI analyses is demonstrated that should be flexibly implementable across a variety of software platforms. We demonstrate how application of this technique impacts our own data, modifying previous conclusions about brain development. These results suggest the need for greater care in dealing with subject motion, and the need to critically revisit previous rs-fcMRI work that may not have adequately controlled for effects of transient subject movements.

Explaining variation in sweat sodium concentration: effect of individual characteristics and exercise, environmental, and dietary factors.

This study determined the relative importance of several individual characteristics and dietary, environmental, and exercise factors in determining sweat [Na+] during exercise. Data from 1944 sweat tests were compiled for a retrospective analysis. Stepwise multiple regression (P < 0.05 threshold for inclusion) and T values were used to express the relative importance of each factor in a model. Three separate models were developed based on available independent variables: model 1 (1,944 sweat tests from 1,304 subjects); model 2 (subset with energy expenditure: 1,003 sweat tests from 607 subjects); model 3 (subset with energy expenditure, dietary sodium, and V̇o2max: n = 48). Whole body sweat [Na+] was predicted from forearm sweat patches in models 1 and 2 and directly measured using whole body washdown in model 3. There were no significant effects of age group, race/ethnicity, relative humidity, exercise duration, pre-exercise urine specific gravity, exercise fluid balance, or dietary or exercise sodium intake on any model. Significant predictors in model 1 (adjusted r2 = 0.17, P < 0.001) were season of the year (warm, T = -6.8), exercise mode (cycling, T = 6.8), sex (male, T = 4.9), whole body sweating rate (T = 4.5), and body mass (T = -3.0). Significant predictors in model 2 (adjusted r2 = 0.19, P < 0.001) were season of the year (warm, T = -5.2), energy expenditure (T = 4.7), exercise mode (cycling, T = 3.6), air temperature (T = 3.0), and sex (male, T = 2.7). The only significant predictor in model 3 (r2 = 0.23, P < 0.001) was energy expenditure (T = 3.8). In summary, the models accounted for 17%-23% of the variation in whole body sweat [Na+] and energy expenditure and season of the year (proxy for heat acclimatization) were the most important factors.NEW & NOTEWORTHY This comprehensive analysis of a large, diverse data set contributes to our overall understanding of the factors that influence whole body sweat [Na+]. The main finding was that energy expenditure was directly associated with whole body sweat [Na+], potentially via the relation between energy expenditure and whole body sweating rate (WBSR). Warmer months (proxy for heat acclimatization) were associated with lower whole body sweat [Na+]. Exercise mode, air temperature, and sex may also have small effects, but other variables (age group, race/ethnicity, fluid balance, sodium intake, relative V̇o2max) had no association with whole body sweat [Na+]. Taken together, the models explained 17%-23% of the variation in whole body sweat [Na+].

WT1 mutations in T-ALL.

The molecular mechanisms involved in disease progression and relapse in T-cell acute lymphoblastic leukemia (T-ALL) are poorly understood. We used single nucleotide polymorphism array analysis to analyze paired diagnostic and relapsed T-ALL samples to identify recurrent genetic alterations in T-ALL. This analysis showed that diagnosis and relapsed cases have common genetic alterations, but also that relapsed samples frequently lose chromosomal markers present at diagnosis, suggesting that relapsed T-ALL emerges from an ancestral clone different from the major leukemic population at diagnosis. In addition, we identified deletions and associated mutations in the WT1 tumor suppressor gene in 2 of 9 samples. Subsequent analysis showed WT1 mutations in 28 of 211 (13.2%) of pediatric and 10 of 85 (11.7%) of adult T-ALL cases. WT1 mutations present in T-ALL are predominantly heterozygous frameshift mutations resulting in truncation of the C-terminal zinc finger domains of this transcription factor. WT1 mutations are most prominently found in T-ALL cases with aberrant rearrangements of the oncogenic TLX1, TLX3, and HOXA transcription factor oncogenes. Survival analysis demonstrated that WT1 mutations do not confer adverse prognosis in pediatric and adult T-ALL. Overall, these results identify the presence of WT1 mutations as a recurrent genetic alteration in T-ALL.

Advance care planning in advanced cancer: can it be achieved? An exploratory randomized patient preference trial of a care planning discussion.

OBJECTIVE: Little is known about the effectiveness of advance care planning in the United Kingdom, although policy documents recommend that it should be available to all those with life-limiting illness. METHOD: An exploratory patient preference randomized controlled trial of advance care planning discussions with an independent mediator (maximum three sessions) was conducted in London outpatient oncology clinics and a nearby hospice. Seventy-seven patients (mean age 62 years, 39 male) with various forms of recurrent progressive cancer participated, and 68 (88%) completed follow-up at 8 weeks. Patients completed visual analogue scales assessing perceived ability to discuss end-of-life planning with healthcare professionals or family and friends (primary outcome), happiness with the level of communication, and satisfaction with care, as well as a standardized measure of anxiety and depression. RESULTS: Thirty-eight patients (51%) showed preference for the intervention. Discussions with professionals or family and friends about the future increased in the intervention arms, whether randomized or preference, but happiness with communication was unchanged or worse, and satisfaction with services decreased. Trial participation did not cause significant anxiety or depression and attrition was low. SIGNIFICANCE OF RESULTS: A randomized trial of advance care planning is possible. This study provides new evidence on its acceptability and effectiveness for patients with advanced cancer.

Advance care planning discussions in advanced cancer: analysis of dialogues between patients and care planning mediators.

OBJECTIVE: Advance care planning (ACP) provides patients with an opportunity to consider, discuss, and plan their future care with health professionals. Numerous policy documents recommend that ACP should be available to all with life-limiting illness. METHOD: Forty patients with recurrent progressive cancer completed one or more ACP discussions with a trained planning mediator using a standardized topic guide. Fifty-two interviews were transcribed verbatim and analyzed for qualitative thematic content. RESULTS: Most patients had not spoken extensively to health professionals or close persons about the future. Their concerns related to experiencing distressing symptoms or worrying how family members would cope. Some patients wished for more accurate information and were unaware of their options for care. Many felt it was doctors' responsibility to initiate such discussions, but perceived that their doctors were reluctant to do so. However, some patients felt that the time was not yet right for these conversations. SIGNIFICANCE OF RESULTS: This article reports on the recorded content of ACP discussions. The extent to which patients want to engage in ACP is variable, and support and training are needed for health professionals to initiate such discussions. Our findings do not fully support the current United Kingdom policy of introducing ACP early in life-threatening disease.