Flight motor networks modulate primary olfactory processing in the moth Manduca sexta.

Nervous systems must distinguish sensory signals derived from an animal's own movements (reafference) from environmentally derived sources (exafference). To accomplish this, motor networks producing reafference transmit motor information, via a corollary discharge circuit (CDC), to affected sensory networks, modulating sensory function during behavior. While CDCs have been described in most sensory modalities, none have been observed projecting to an olfactory pathway. In moths, two mesothoracic to deutocerebral histaminergic neurons (MDHns) project from flight sensorimotor centers in the mesothoracic neuromere to the antennal lobe (AL), where they provide the sole source of histamine (HA), but whether they represent a CDC is unknown. We demonstrate that MDHn spiking activity is positively correlated with wing-motor output and increased before bouts of motor activity, suggesting that MDHns communicate global locomotor state, rather than providing a precisely timed motor copy. Within the AL, HA application sharpened entrainment of projection neuron responses to odor stimuli embedded within simulated wing-beat-induced flows, whereas MDHn axotomy or AL HA receptor (HA-r) blockade reduced entrainment. This finding is consistent with higher-order CDCs, as the MDHns enhanced rather than filtered entrainment of AL projection neurons. Finally, HA-r blockade increased odor detection and discrimination thresholds in behavior assays. These results establish MDHns as a CDC that modulates AL temporal resolution, enhancing odor-guided behavior. MDHns thus appear to represent a higher-order CDC to an insect olfactory pathway; this CDC's unique nature highlights the importance of motor-to-sensory signaling as a context-specific mechanism that fine-tunes sensory function.

A Low-Carbohydrate Ketogenic Diet Reduces Body Mass Without Compromising Performance in Powerlifting and Olympic Weightlifting Athletes.

Greene, DA, Varley, BJ, Hartwig, TB, Chapman, P, and Rigney, M. A low-carbohydrate ketogenic diet reduces body mass without compromising performance in powerlifting and Olympic weightlifting athletes. J Strength Cond Res 32(12): 3382-3391, 2018-Weight class athletes use weight-making strategies to compete in specific weight categories with an optimum power-to-weight ratio. There is evidence that low carbohydrate diets might offer specific advantages for weight reduction without the negative impact on strength and power previously hypothesized to accompany carbohydrate restriction. Therefore, the purpose of this study was to determine whether a low-carbohydrate ketogenic diet (LCKD) could be used as a weight reduction strategy for athletes competing in the weight class sports of powerlifting and Olympic weightlifting. Fourteen intermediate to elite competitive lifting athletes (age 34 ± 10.5, n = 5 female) consumed an ad libitum usual diet (UD) (>250 g daily intake of carbohydrates) and an ad libitum LCKD (≤50 g or ≤10% daily intake of carbohydrates) in random order, each for 3 months in a crossover design. Lifting performance, body composition, resting metabolic rate, blood glucose, and blood electrolytes were measured at baseline, 3 months, and 6 months. The LCKD phase resulted in significantly lower body mass (-3.26 kg, p = 0.038) and lean mass (-2.26 kg, p = 0.016) compared with the UD phase. Lean mass losses were not reflected in lifting performances that were not different between dietary phases. No other differences in primary or secondary outcome measures were found between dietary phases. Weight class athletes consuming an ad libitum LCKD decreased body mass and achieved lifting performances that were comparable with their UD. Coaches and athletes should consider using an LCKD to achieve targeted weight reduction goals for weight class sports.

Co-option of a motor-to-sensory histaminergic circuit correlates with insect flight biomechanics.

Nervous systems must adapt to shifts in behavioural ecology. One form of adaptation is neural exaptation, in which neural circuits are co-opted to perform additional novel functions. Here, we describe the co-option of a motor-to-somatosensory circuit into an olfactory network. Many moths beat their wings during odour-tracking, whether walking or flying, causing strong oscillations of airflow around the antennae, altering odour plume structure. This self-induced sensory stimulation could impose selective pressures that influence neural circuit evolution, specifically fostering the emergence of corollary discharge circuits. In Manduca sexta, a pair of mesothoracic to deutocerebral histaminergic neurons (MDHns), project from the mesothoracic neuromere to both antennal lobes (ALs), the first olfactory neuropil. Consistent with a hypothetical role in providing the olfactory system with a corollary discharge, we demonstrate that the MDHns innervate the ALs of advanced and basal moths, but not butterflies, which differ in wing beat and flight pattern. The MDHns probably arose in crustaceans and in many arthropods innervate mechanosensory areas, but not the olfactory system. The MDHns, therefore, represent an example of architectural exaptation, in which neurons that provide motor output information to mechanosensory regions have been co-opted to provide information to the olfactory system in moths.

The effect of ice-slushy consumption on plasma vasoactive intestinal peptide during prolonged exercise in the heat.

The aim of this study was to determine the effect of exercise in the heat on thermoregulatory responses and plasma vasoactive intestinal peptide concentration (VIP) and whether it is modulated by ice-slushy consumption. Ten male participants cycled at 62% V̇O2max for 90min in 32°C and 40% relative humidity. A thermoneutral (37°C) or ice-slushy (-1°C) sports drink was given at 3.5mlkg(-1) body mass every 15min during exercise. VIP and rectal temperature increased during exercise (mean±standard deviation: 4.6±4.4pmolL(-1), P=0.005; and 1.3±0.4°C, P<0.001 respectively) and were moderately associated (r=0.35, P=0.008). While rectal temperature and VIP were not different between trials, ice-slushy significantly reduced heat storage (P=0.010) and skin temperature (time×trial interaction P=0.038). It appears that VIP does not provide the signal linking cold beverage ingestion and lower skin temperature in the heat.

Applied Force Alters Sensorineural and Peripheral Vascular Function in a Rat Model of Hand-Arm Vibration Syndrome.

OBJECTIVE: This study described the effects of applied force (grip) on vascular and sensorineural function in an animal model of hand-arm vibration syndrome (HAVS). METHODS: Rat tails were exposed to 0, 2, or 4 N of applied force 4 hr/d for 10 days. Blood flow and sensitivity to transcutaneous electrical stimulation and pressure were measured. RESULTS: Applied force increased blood flow but reduced measures of arterial plasticity. Animals exposed to force tended to be more sensitive to 250-Hz electrical stimulation and pressure applied to the tail. CONCLUSIONS: Effects of applied force on blood flow and sensation are different than those of vibration. Studies examining co-exposures to force and vibration will provide data that can be used to determine how these factors affect risk of workers developing vascular and sensorineural dysfunction (ie, HAVS).

A single-vector intersectional AAV strategy for interrogating cellular diversity and brain function.

As discovery of cellular diversity in the brain accelerates, so does the need for tools that target cells based on multiple features. Here we developed Conditional Viral Expression by Ribozyme Guided Degradation (ConVERGD), an adeno-associated virus-based, single-construct, intersectional targeting strategy that combines a self-cleaving ribozyme with traditional FLEx switches to deliver molecular cargo to specific neuronal subtypes. ConVERGD offers benefits over existing intersectional expression platforms, such as expanded intersectional targeting with up to five recombinase-based features, accommodation of larger and more complex payloads and a vector that is easy to modify for rapid toolkit expansion. In the present report we employed ConVERGD to characterize an unexplored subpopulation of norepinephrine (NE)-producing neurons within the rodent locus coeruleus that co-express the endogenous opioid gene prodynorphin (Pdyn). These studies showcase ConVERGD as a versatile tool for targeting diverse cell types and reveal Pdyn-expressing NE+ locus coeruleus neurons as a small neuronal subpopulation capable of driving anxiogenic behavioral responses in rodents.

The effect of nitrate supplementation on exercise performance in healthy individuals: a systematic review and meta-analysis.

The purpose of this review was to examine the effect of nitrate supplementation on exercise performance by systematic review and meta-analysis of controlled human studies. A search of four electronic databases and cross-referencing found 17 studies investigating the effect of inorganic nitrate supplementation on exercise performance that met the inclusion criteria. Beetroot juice and sodium nitrate were the most common supplements, with doses ranging from 300 to 600 mg nitrate and prescribed in a manner ranging from a single bolus to 15 days of regular ingestion. Pooled analysis showed a significant moderate benefit (ES = 0.79, 95% CI: 0.23-1.35) of nitrate supplementation on performance for time to exhaustion tests (p = .006). There was a small but insignificant beneficial effect on performance for time trials (ES = 0.11, 95% CI: -0.16-0.37) and graded exercise tests (ES = 0.26, 95% CI: -0.10-0.62). Qualitative analysis suggested that performance benefits are more often observed in inactive to recreationally active individuals and when a chronic loading of nitrate over several days is undertaken. Overall, these results suggest that nitrate supplementation is associated with a moderate improvement in constant load time to exhaustion tasks. Despite not reaching statistical significance, the small positive effect on time trial or graded exercise performance may be meaningful in an elite sport context. More data are required to clarify the effect of nitrate supplementation on exercise performance and to elucidate the optimal way to implement supplementation.

The effect of ice slushy ingestion and mouthwash on thermoregulation and endurance performance in the heat.

PURPOSE: The purpose of this study was to establish whether sensory factors associated with cold-beverage ingestion exert an ergogenic effect on endurance performance independent of thermoregulatory or cardiovascular factors. METHODS: Ten males performed three trials involving 90 min of steady state cycling (SS; 62% VO2max) in the heat (32.1 ± 0.9 °C, 40 ± 2.4% relative humidity) followed by a 4 kJ/kg body mass time trial (TT). During SS, participants consumed an identical volume (260 ± 38 g) of sports beverage (7.4% carbohydrate) every 15 min as either ice slushy (-1 °C; ICE), thermoneutral liquid (37 °C; CON), or thermoneutral liquid consumption with expectorated ice slushy mouthwash (WASH). RESULTS: Rectal temperature, hydration status, heart rate, and skin blood flow were not different between trials. Gastrointestinal (pill) temperature was lower in ICE (35.6 ± 2.7 °C) versus CON (37.4 ± 0.7 °C, p = .05). Heat storage tended to be lower with ICE during SS (14.7 ± 8.4 W.m(-2), p = .08) and higher during TT (68.9 ± 38.6 W.m(-2), p = .03) compared with CON (22.1 ± 6.6 and 31.4 ± 27.6 W.m(-2)). ICE tended to lower the rating of perceived exertion (RPE, 12.9 ± 0.6, p = .05) and improve thermal comfort (TC, 4.5 ± 0.2; p = .01) vs. CON (13.8 ± 1.0 and 5.2 ± 0.2 respectively). WASH RPE (13.0 ± 0.8) and TC (4.8 ± 0.2) tended to be lower versus CON (p = .07 and p = .09 respectively). ICE improved performance (18:28 ± 1:03) compared with CON (20:24 ± 1:46) but not WASH (19:45 ± 1:43). CONCLUSION: Improved performance with ICE ingestion likely resulted from the creation of a gastrointestinal heat sink, reducing SS heat storage. Although the benefits of cold-beverage consumption are more potent when there is ingestion, improved RPE, TC, and meaningful performance improvement with WASH supports an independent sensory effect of presenting a cold stimulus to the mouth.

Case study: beverage temperature at aid stations in ironman triathlon.

PURPOSE: The aim of this study was to measure the effect of environmental conditions and aid-station beverage- cooling practices on the temperature of competitor beverages. METHODS: Environmental and beverage temperatures were measured at three cycling and two run course aid stations at the 2010 Langkawi, Malaysia (MA), and Port Macquarie, Australia (AU), Ironman triathlon events. To measure the specific effect of radiant temperature, additional fluid-filled (600 ml) drink bottles (n = 12) were cooled overnight (C) and then placed in direct sun (n = 6) or shade (n = 6) near to a cycle aid station at AU. RESULTS: During both events, beverage temperature increased over time (p < .05) as environmental conditions, particularly radiant temperature increased (p < .05). Mean beverage temperature ranged between 14-26°C and during both events was above the palatable range (15-22°C) for extended periods. At AU, bottles placed in direct sunlight heated faster (6.9 ± 2.3 °C·h-1) than those in the shade (4.8 ±1.1°C·h-1, p = .05). CONCLUSION: Simple changes to Ironman aid-station practices, including shade and chilling beverages with ice, result in the provision of cooler beverages. Future studies should investigate whether provision of cool beverages at prolonged endurance events influences heat-illness incidence, beverage-consumption patterns, and competitor performance.

A Novel Single Vector Intersectional AAV Strategy for Interrogating Cellular Diversity and Brain Function.

As the discovery of cellular diversity in the brain accelerates, so does the need for functional tools that target cells based on multiple features, such as gene expression and projection target. By selectively driving recombinase expression in a feature-specific manner, one can utilize intersectional strategies to conditionally promote payload expression only where multiple features overlap. We developed Conditional Viral Expression by Ribozyme Guided Degradation (ConVERGD), a single-construct intersectional targeting strategy that combines a self-cleaving ribozyme with traditional FLEx switches. ConVERGD offers benefits over existing platforms, such as expanded intersectionality, the ability to accommodate larger and more complex payloads, and a vector design that is easily modified to better facilitate rapid toolkit expansion. To demonstrate its utility for interrogating neural circuitry, we employed ConVERGD to target an unexplored subpopulation of norepinephrine (NE)-producing neurons within the rodent locus coeruleus (LC) identified via single-cell transcriptomic profiling to co-express the stress-related endogenous opioid gene prodynorphin (Pdyn). These studies showcase ConVERGD as a versatile tool for targeting diverse cell types and reveal Pdyn-expressing NE+ LC neurons as a small neuronal subpopulation capable of driving anxiogenic behavioral responses in rodents.

Influence of Beverage Temperature on Palatability and Fluid Ingestion During Endurance Exercise: a systematic review.

Beverage palatability is known to influence fluid consumption during exercise and may positively influence hydration status and help to prevent fatigue, heat illness and decreased performance. PURPOSE: The aims of this review were to evaluate the effect of beverage temperature on fluid intake during exercise and investigate the influence of beverage temperature on palatability. METHODS: Citations from multiple databases were searched from the earliest record to November 2010 using the terms 'beverage', 'fluid' or 'water' and 'palatability', 'preference', 'feeding' and 'drinking behaviour' and 'temperature'. Included studies (n=13) needed to use adult (≥18yr) human participants, have beverage temperatures ≤50°C and measure consumption during exercise and/or palatability. RESULTS: All studies (n=8) reporting palatability indicated cold (0- 10°C) or cool (10-22°C) beverages were preferred to warmer (control, ≥22°C). A meta-analysis on studies (n=5) reporting fluid consumption revealed that participants consumed ~50% (effect size=1.4, 0.75 to 2.04, 95% CI) more cold/cool beverages than control during exercise. Sub-analysis of studies assessing hydration status (n=4) when consuming cool/cold compared to warm beverages demonstrated that dehydration during exercise was reduced by 1.3% of body weight (1.6 to 0.9%, 95% CI) (p<0.001). CONCLUSION: Cool beverage temperatures (<22°C) significantly increased fluid palatability, consumption and hydration during exercise compared to control (≥22°C).

Influence of beverage temperature on palatability and fluid ingestion during endurance exercise: a systematic review.

UNLABELLED: Beverage palatability is known to influence fluid consumption during exercise and may positively influence hydration status and help prevent fatigue, heat illness, and decreased performance. PURPOSE: The aims of this review were to evaluate the effect of beverage temperature on fluid intake during exercise and investigate the influence of beverage temperature on palatability. METHODS: Citations from multiple databases were searched from the earliest record to November 2010 using the terms beverage, fluid, or water and palatability, preference, feeding, and drinking behavior and temperature. Included studies (N = 14) needed to use adult (≥18 yr) human participants, have beverage temperatures ≤50 °C, and measure consumption during exercise and/or palatability. RESULTS: All studies reporting palatability (n = 10) indicated that cold (0-10 °C) or cool (10-22 °C) beverages were preferred to warmer ones (control, ≥22 °C). A meta-analysis on studies reporting fluid consumption (n = 5) revealed that participants consumed ~50% (effect size = 1.4, 0.75-2.04, 95% CI) more cold/cool beverages than control during exercise. Subanalysis of studies assessing hydration status (n = 4) with consumption of cool/cold vs. warm beverages demonstrated that dehydration during exercise was reduced by 1.3% of body weight (1.6-0.9%, 95% CI; p < .001). CONCLUSION: Cool beverage temperatures (<22 °C) significantly increased fluid palatability, fluid consumption, and hydration during exercise vs. control (≥22 -°C).

Cardiovascular strain impairs prolonged self-paced exercise in the heat.

It has been proposed that self-paced exercise in the heat is regulated by an anticipatory reduction in work rate based on the rate of heat storage. However, performance may be impaired by the development of hyperthermia and concomitant rise in cardiovascular strain increasing relative exercise intensity. This study evaluated the influence of thermal strain on cardiovascular function and power output during self-paced exercise in the heat. Eight endurance-trained cyclists performed a 40 km simulated time trial in hot (35°C) and thermoneutral conditions (20°C), while power output, mean arterial pressure, heart rate, oxygen uptake and cardiac output were measured. Time trial duration was 64.3 ± 2.8 min (242.1 W) in the hot condition and 59.8 ± 2.6 min (279.4 W) in the thermoneutral condition (P < 0.01). Power output in the heat was depressed from 20 min onwards compared with exercise in the thermoneutral condition (P < 0.05). Rectal temperature reached 39.8 ± 0.3 (hot) and 38.9 ± 0.2°C (thermoneutral; P < 0.01). From 10 min onwards, mean skin temperature was ~7.5°C higher in the heat, and skin blood flow was significantly elevated (P < 0.01). Heart rate was ~8 beats min(-1) higher throughout hot exercise, while stroke volume, cardiac output and mean arterial pressure were significantly depressed compared with the thermoneutral condition (P < 0.05). Peak oxygen uptake measured during the final kilometre of exercise at maximal effort reached 77 (hot) and 95% (thermoneutral) of pre-experimental control values (P < 0.01). We conclude that a thermoregulatory-mediated rise in cardiovascular strain is associated with reductions in sustainable power output, peak oxygen uptake and maximal power output during prolonged, intense self-paced exercise in the heat.

The role of dietary fatty acids in predicting myocardial structure in fat-fed rats.

BACKGROUND: Obesity increases the risk for development of cardiomyopathy in the absence of hypertension, diabetes or myocardial ischemia. Not all obese individuals, however, progress to heart failure. Indeed, obesity may provide protection from cardiovascular mortality in some populations. The fatty acid milieu, modulated by diet, may modify obesity-induced myocardial structure and function, lending partial explanation for the array of cardiomyopathic phenotype in obese individuals. METHODS: Adult male Sprague-Dawley rats were fed 1 of the following 4 diets for 32 weeks: control (CON); 50% saturated fat (SAT); 40% saturated fat + 10% linoleic acid (SAT+LA); 40% saturated fat + 10% α-linolenic acid (SAT+ALA). Serum leptin, insulin, glucose, free fatty acids and triglycerides were quantitated. In vivo cardiovascular outcomes included blood pressure, heart rate and echocardiographic measurements of structure and function. The rats were sacrificed and myocardium was processed for fatty acid analysis (TLC-GC), and evaluation of potential modifiers of myocardial structure including collagen (Masson's trichrome, hydroxyproline quantitation), lipid (Oil Red O, triglyceride quantitation) and myocyte cross sectional area. RESULTS: Rats fed SAT+LA and SAT+ALA diets had greater cranial LV wall thickness compared to rats fed CON and SAT diets, in the absence of hypertension or apparent insulin resistance. Treatment was not associated with changes in myocardial function. Myocardial collagen and triglycerides were similar among treatment groups; however, rats fed the high-fat diets, regardless of composition, demonstrated increased myocyte cross sectional area. CONCLUSIONS: Under conditions of high-fat feeding, replacement of 10% saturated fat with either LA or ALA is associated with thickening of the cranial LV wall, but without concomitant functional changes. Increased myocyte size appears to be a more likely contributor to early LV thickening in response to high-fat feeding. These findings suggest that myocyte hypertrophy may be an early change leading to gross LV hypertrophy in the hearts of "healthy" obese rats, in the absence of hypertension, diabetes and myocardial ischemia.

Neuromuscular function following prolonged intense self-paced exercise in hot climatic conditions.

Muscle weakness following constant load exercise under heat stress has been associated with hyperthermia-induced central fatigue. However, evidence of central fatigue influencing intense self-paced exercise in the heat is lacking. The purpose of this investigation was to evaluate force production capacity and central nervous system drive in skeletal muscle pre- and post-cycle ergometer exercise in hot and cool conditions. Nine trained male cyclists performed a 20-s maximal voluntary isometric contraction (MVC) prior to (control) and following a 40-km time trial in hot (35°C) and cool (20°C) conditions. MVC force production and voluntary activation of the knee extensors was evaluated via percutaneous tetanic stimulation. In the cool condition, rectal temperature increased to 39.0°C and reached 39.8°C in the heat (P < 0.01). Following exercise in the hot and cool conditions, peak force declined by ~90 and ~99 N, respectively, compared with control (P < 0.01). Mean force decreased by 15% (hot) and 14% (cool) (P < 0.01 vs. control). Voluntary activation during the post-exercise MVC declined to 93.7% (hot) and 93.9% (cool) (P < 0.05 vs. control). The post-exercise decline in voluntary activation represented ~20% of the decrease in mean force production in both conditions. Therefore, the additional increase in rectal temperature did not exacerbate the loss of force production following self-paced exercise in the heat. The impairment in force production indicates that the fatigue exhibited by the quadriceps is mainly of peripheral origin and a consequence of the prolonged contractile activity associated with exercise.

Mass drug administration of ivermectin in south-eastern Senegal reduces the survivorship of wild-caught, blood fed malaria vectors.

BACKGROUND: In south-eastern Senegal, malaria and onchocerciasis are co-endemic. Onchocerciasis in this region has been controlled by once or twice yearly mass drug administration (MDA) with ivermectin (IVM) for over fifteen years. Since laboratory-raised Anopheles gambiae s.s. are susceptible to ivermectin at concentrations found in human blood post-ingestion of IVM, it is plausible that a similar effect could be quantified in the field, and that IVM might have benefits as a malaria control tool. METHODS: In 2008 and 2009, wild-caught blood fed An. gambiae s.l. mosquitoes were collected from huts of three pairs of Senegalese villages before and after IVM MDAs. Mosquitoes were held in an insectary to assess their survival rate, subsequently identified to species, and their blood meals were identified. Differences in mosquito survival were statistically analysed using a Glimmix model. Lastly, changes in the daily probability of mosquito survivorship surrounding IVM MDAs were calculated, and these data were inserted into a previously developed, mosquito age-structured model of malaria transmission. RESULTS: Anopheles gambiae s.s. (P < 0.0001) and Anopheles arabiensis (P = 0.0191) from the treated villages had significantly reduced survival compared to those from control villages. Furthermore, An gambiae s.s. caught 1-6 days after MDA in treated villages had significantly reduced survival compared to control village collections (P = 0.0003), as well as those caught pre-MDA (P < 0.0001) and >7 days post-MDA (P < 0.0001). The daily probability of mosquito survival dropped >10% for the six days following MDA. The mosquito age-structured model of malaria transmission demonstrated that a single IVM MDA would reduce malaria transmission (Ro) below baseline for at least eleven days, and that repeated IVM MDAs would result in a sustained reduction in malaria Ro. CONCLUSIONS: Ivermectin MDA significantly reduced the survivorship of An. gambiae s.s. for six days past the date of the MDA, which is sufficient to temporarily reduce malaria transmission. Repeated IVM MDAs could be a novel and integrative malaria control tool in areas with seasonal transmission, and which would have simultaneous impacts on neglected tropical diseases in the same villages.

Effect of drink temperature on core temperature and endurance cycling performance in warm, humid conditions.

The aims of this study were to determine the effect of cold (4 °C) and thermoneutral (37 °C) beverages on thermoregulation and performance in the heat and to explore sensory factors associated with ingesting a cold stimulus. Seven males (age 32.8 ± 6.1 years, [V(.)]O(2peak) 59.4 ± 6.6 ml x kg(-1) x min(-1)) completed cold, thermoneutral, and thermoneutral + ice trials in randomized order. Participants cycled for 90 min at 65%[V(.)]O(2peak) followed by a 15-min performance test at 28 °C and 70% relative humidity. They ingested 2.3 ml x kg(-1) of a 7.4% carbohydrate-electrolyte solution every 10 min during the 90-min steady-state exercise including 30 ml ice puree every 5 min in the ice trial. Absolute changes in skin temperature (0.22 ± 1.1 °C vs. 1.14 ± 0.9 °C; P = 0.02), mean body temperature (1.2 ± 0.3 vs. 1.6 ± 0.3 °C; P = 0.03), and heat storage were lower across the 90-min exercise bout for the cold compared with the thermoneutral trial. Significant improvements (4.9 ± 2.4%, P < 0.01) in performance were observed with cold but no significant differences were detected with ice. Consumption of cold beverages during prolonged exercise in the heat improves body temperature measures and performance. Consumption of ice did not reveal a sensory response, but requires further study. Beverages consumed by athletes exercising in the heat should perhaps be cold for performance and safety reasons.

Exploring survey participation, data combination, and research validity in a substance use study: an application of hierarchical linear modeling.

A sound decision regarding combination of datasets is critical for research validity. Data were collected between 1996 and 2000 via a 99-item survey of substance use behaviors. Two groups of 7th-12th grade students in predominately White communities are compared: 166,578 students from 193 communities with high survey participation and 41,259 students from 65 communities with lower participation. Hierarchical logistic models are used to explore whether the two datasets may be combined for further study of community-level substance use effects. "Scenario analysis" is introduced. Results suggest the datasets may reasonably be combined. Limitations and further research are discussed.

Experimental design, power and sample size for animal reproduction experiments.

The present paper concerns statistical issues in the design of animal reproduction experiments, with emphasis on the problems of sample size determination and power calculations. We include examples and non-technical discussions aimed at helping researchers avoid serious errors that may invalidate or seriously impair the validity of conclusions from experiments. Screen shots from interactive power calculation programs and basic SAS power calculation programs are presented to aid in understanding statistical power and computing power in some common experimental situations. Practical issues that are common to most statistical design problems are briefly discussed. These include one-sided hypothesis tests, power level criteria, equality of within-group variances, transformations of response variables to achieve variance equality, optimal specification of treatment group sizes, 'post hoc' power analysis and arguments for the increased use of confidence intervals in place of hypothesis tests.

Pharmacokinetics and pharmacodynamics of morphine in llamas.

OBJECTIVE: To assess the pharmacokinetics and pharmacodynamics of morphine in llamas. ANIMALS: 6 healthy adult llamas. PROCEDURES: Llamas received morphine sulfate in a randomized crossover design. In phase 1, they received IV or IM administration of morphine at 0.05 or 0.5 mg/kg, respectively; in phase 2, they received IV administration of morphine at 0.05, 0.25, or 0.5 mg/kg. Plasma morphine and morphine-6-glucuronide concentrations were determined by validated methods. Body temperature, heart rate, respiratory rate, sedation, and analgesia were assessed and compared with plasma concentrations by regression analysis. RESULTS: Total body clearance was similar between IV administration of morphine sulfate at 0.25 and 0.5 mg/kg (mean +/- SD, 25.3 +/- 6.9 mL/min/kg and 27.3 +/- 5.9 mL/min/kg, respectively), and linearity was demonstrated between these doses. Bioavailability of morphine following IM administration at 0.5 mg/kg was 120 +/- 30%. Body temperature and sedation increased as the dose of morphine administered increased. Heart rate was unaffected by varying doses. Respiratory rate decreased as dose increased. Analgesia was difficult to assess as a result of high individual variability. Intravenous administration of morphine at 0.25 mg/kg provided the most consistent increase in tolerance to electric stimulation. Pharmacodynamic modeling revealed a sigmoidal relationship between plasma concentration and sedation score. CONCLUSIONS AND CLINICAL RELEVANCE: Morphine was characterized by a large apparent volume of distribution and high systemic clearance in llamas. A prolonged half-life was observed with IM injection. Intravenous administration of morphine sulfate at 0.25 mg/kg every 4 hours is suggested for further study.