Search

BackgroundRecent developments in computational psychiatry have led to the hypothesis that mood represents an expectation (prior belief) on the likely interoceptive consequences of action (i.e. emotion). This stems from ideas about how the brain navigates its external world by minimising an upper bound on surprisal (free energy) of sensory information and echoes developments in other perceptual domains.AimsIn this paper we aim to present a simple partial observable Markov decision process that models mood updating in response to stressful or non-stressful environmental fluctuations while seeking to minimise surprisal in relation to prior beliefs about the likely interoceptive signals experienced with specific actions (attenuating or amplifying stress and pleasure signals).MethodWe examine how, by altering these prior beliefs we can model mood updating in depression, mania and anxiety.ResultsWe discuss how these models provide a computational account of mood and its related psychopathology and relate it to previous research in reward processing.ConclusionsModels such as this can provide hypotheses for experimental work and also open up the potential modelling of predicted disease trajectories in individual patients.

The use of diet and exercise has become the cornerstone to treatment of overfatness issues. Yet, the implementation of such factors into lifestyle changes has not been able to meet intrinsic expectations or desires and has led to continuous repetition of short-term success within a coercive environment that is followed by rebound leading to secondary short-term success, that is yo-yo’ing. Even though this has become common, there has been little insight into how we might be able to improve suggestions for diet and exercise to better encourage long-term success as opposed to the short-term gains that are regularly met. In this commentary, we offer a narrative review describing how the use of behavioural analytic methodologies and techniques might allow for the development of self-selective lifestyle modifications (e.g. changes to diet, use of exercise) and choices in behaviour that better serve individuals attempting to reverse the health issues associated with overfatness, without the sense of their being coerced into their choices.

The testis transcriptome is highly complex and includes RNAs that potentially hybridize to form double-stranded RNA (dsRNA). We isolated dsRNA using the monoclonal J2 antibody and deep-sequenced the enriched samples from testes of juvenile Dicer1 knockout mice, age-matched controls, and adult animals. Comparison of our data set with recently published data from mouse liver revealed that the dsRNA transcriptome in testis is markedly different from liver: In testis, dsRNA-forming transcripts derive from mRNAs including promoters and immediate downstream regions, whereas in somatic cells they originate more often from introns and intergenic transcription. The genes that generate dsRNA are significantly expressed in isolated male germ cells with particular enrichment in pachytene spermatocytes. dsRNA formation is lower on the sex (X and Y) chromosomes. The dsRNA transcriptome is significantly less complex in juvenile mice as compared to adult controls and, possibly as a consequence, the knockout of Dicer1 has only a minor effect on the total number of transcript peaks associated with dsRNA. The comparison between dsRNA-associated genes in testis and liver with a reported set of genes that produce endogenous siRNAs reveals a significant overlap in testis but not in liver. Testis dsRNAs also significantly associate with natural antisense genes—again, this feature is not observed in liver. These findings point to a testis-specific mechanism involving natural antisense transcripts and the formation of dsRNAs that feed into the RNA interference pathway, possibly to mitigate the mutagenic impacts of recombination and transposon mobilization.

Background & Aims: Obesity-associated inflammation is a key player in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). However, the role of macrophage scavenger receptor 1 (MSR1, CD204) remains incompletely understood. Methods: A total of 170 NAFLD liver biopsies were processed for transcriptomic analysis and correlated with clinicopathological features. Msr1(-/-) and wild-type mice were subjected to a 16-week high-fat and high-cholesterol diet. Mice and ex vivo human liver slices were treated with a monoclonal antibody against MSR1. Genetic susceptibility was assessed using genome-wide association study data from 1,483 patients with NAFLD and 430,101 participants of the UK Biobank. Results: MSR1 expression was associated with the occurrence of hepatic lipid-laden foamy macrophages and correlated with the degree of steatosis and steatohepatitis in patients with NAFLD. Mice lacking Msr1 were protected against diet-induced metabolic disorder, showing fewer hepatic foamy macrophages, less hepatic inflammation, improved dyslipidaemia and glucose tolerance, and altered hepatic lipid metabolism. Upon induction by saturated fatty acids, MSR1 induced a pro-inflammatory response via the JNK signalling pathway. In vitro blockade of the receptor prevented the accumulation of lipids in primary macrophages which inhibited the switch towards a proinflammatory phenotype and the release of cytokines such as TNF-alpha Targeting MSR1 using monoclonal antibody therapy in an obesity-associated NAFLD mouse model and human liver slices resulted in the prevention of foamy macrophage formation and inflammation. Moreover, we identified that rs41505344, a polymorphism in the upstream transcriptional region of MSR1, was associated with altered serum triglycerides and aspartate aminotransferase levels in a cohort of over 400,000 patients. Conclusions: Taken together, our data suggest that MSR1 plays a critical role in lipid-induced inflammation and could thus be a potential therapeutic target for the treatment of NAFLD. Lay summary: Non-alcoholic fatty liver disease (NAFLD) is a chronic disease primarily caused by excessive consumption of fat and sugar combined with a lack of exercise or a sedentary lifestyle. Herein, we show that the macrophage scavenger receptor MSR1, an innate immune receptor, mediates lipid uptake and accumulation in Kupffer cells, resulting in liver inflammation and thereby promoting the progression of NAFLD in humans and mice. (C) 2021 The Authors. Published by Elsevier B.V. on behalf of European Association for the Study of the Liver. Funding Agencies|EPoS (Elucidating Pathways of Steatohepatitis) consortium - Horizon 2020 Framework Program of the European Union [634413]; LITMUS (Liver Investigation: Testing Marker Utility in Steatohepatitis) consortium - Innovative Medicines Initiative (IMI2) Program of the European Union from the EU Horizon 2020 programme [777377]; EFPIA; Newcastle NIHR Biomedical Research Centre; Newcastle University; Wellcome Trust [215542/Z/19/Z]; Knut och Alice Wallenberg Foundation Wallenberg Centre for molecular and translational medicine; University of Gothenburg, Sweden; Ake Wirbergs Research [M18-0121]; Cancerfonfen [19 0352 Pj]; Belgian Federal Science Policy Office (Interuniversity Attraction Poles Program) grant [Network P7/83-HEPRO2]; Rosetrees Trust; Flemish Cancer Society Kom op tegen Kanker; Belgian Cancer Society Stichting tegen Kanker

The purpose of this review is to address what is known, speculated, and hypothesized regarding the issue of hydration and concussions. Based on the question, “What impact does hydration have on the relative risk for suffering concussive injuries along with long-term ramifications that have been associated with concussive (and repeated subconcussive) traumas to the cerebral cortex?,” a search of available literature was performed through June 2019. Deducing from the available literature, we can stipulate that changes in hydration within the cerebral cortex increase the likelihood for disruption of neurofilament proteins, dysregulation of membrane dynamics of the neurons and exacerbate inflammation responses following head trauma. As such, it can be speculated that differences in incidence rates may be attributed to difference in tissue fluid based on athlete demographics, level of whole-body water balance, and degree of tissue dehydration more than selection of sport. Moreover, tissue hydration in combination with other inflammation factors provides the scaffolding for the development of long-term issues (e.g. chronic traumatic encephalopathy) associated with repetitive head trauma in athletes.

Exercise goals that tend to focus on weight loss have varying degrees of long-term success, leading to the phenomenon commonly referenced as yo-yo dieting. The aim of the investigation is to examine the impact of periodized training focused on specific performance goals on long-term weight loss and improvement in fitness for individuals who are overfat with long-term history of yo-yoing. 12 family-related overfat volunteers, 28 ± 5 year and average history of overfatness 8 ± 12 year, completed 108-week periodized training program, broken into 9–12 week mesocycles combining progressive and undulating periodization of exercise choice and training volume for specific improvements in performance measures. Diet was energy density standardized to Cal/d of 90–95% BMR and macronutrient standardized to have a protein intake of 2.2 g/kg BM and carbohydrates intake of 50–100 g/d. There was an average reduction of 35 ± 3% in total body mass and 72 ± 9% fat mass, with a gain of 9 ± 8% in fat-free mass across the length of the study. This was accompanied by 56 ± 3% increase in aerobic fitness and 52 ± 14% reduction in resting heart rate, and strength and endurance gains of 148 ± 65% (squat), 130 ± 10% (dead lift), 110 ± 33% (leg press), 88 ± 27% (lateral pull-downs), 102 ± 36% (bench press), and 720 ± 260% (1-min push-up) and 271 ± 44% (1-min sit-up). Periodized exercise focusing on performance changes, and not weight loss, may provide the stimulus necessary for long-term behavioral modification that is necessary for long-term changes to body composition, where the performance goals may induce a reward response and encourage continuation of exercise for longer durations than had previously attained.

Background: Previous studies have consistently shown increased rates of childhood adversity in chronic fatigue syndrome (CFS). However, such aetiopathogenic studies of CFS are potentially confounded by co-morbidity and misdiagnosis particularly with depression. Purpose: We examined the relationship between rates of childhood adversity using two complimentary approaches (1) a sample of CFS patients who had no lifetime history of depression and (2) a modelling approach. Methods: Childhood trauma questionnaire (CTQ) administered to a sample of 52 participants with chronic fatigue syndrome and 19 controls who did not meet criteria for a psychiatric disorder (confirmed using the Structured Clinical Interview for DSM-IV). Subsequently, Mediation Analysis (Baye’s Rules) was used to establish the risk childhood adversity poses for CFS with and without depression. Results: In a cohort of CFS patients with depression comprehensively excluded, CTQ scores were markedly lower than in all previous studies and, in contrast to these previous studies, not increased compared with healthy controls. Post-hoc analysis showed that CTQ scores correlated with the number of depressive symptoms during the lifetime worst period of low mood. The probability of developing CFS given a history of childhood trauma is 4%, a two-fold increased risk compared to the general population. However, much of this risk is mediated by the concomitant development of major depression. Conclusions: The data suggests that previous studies showing a relationship between childhood adversity and CFS may be attributable to the confounding effects of co-morbid or misdiagnosed depressive disorder. Abbreviations: CFS: Chronic fatigue syndrome; CTQ: Childhood trauma questionnaire; MDD: Major depressive disorder; CA: Childhood adversity; P: Probability

Neuroendocrine data are typically positively skewed and rarely conform to the expectations of a Gaussian distribution. This can be a problem when attempting to analyse results within the framework of the general linear model, which relies on assumptions that residuals in the data are normally distributed. One frequently used method for handling violations of this assumption is to transform variables to bring residuals into closer alignment with assumptions (as residuals are not directly manipulated). This is often attempted through ad hoc traditional transformations such as square root, log and inverse. However, Box and Cox (Box & Cox, ) observed that these are all special cases of power transformations and proposed a more flexible method of transformation for researchers to optimise alignment with assumptions. The goal of this paper is to demonstrate the benefits of the infinitely flexible Box-Cox transformation on neuroendocrine data using syntax in spss. When applied to positively skewed data typical of neuroendocrine data, the majority (~2/3) of cases were brought into strict alignment with Gaussian distribution (i.e. a non-significant Shapiro-Wilks test). Those unable to meet this challenge showed substantial improvement in distributional properties. The biggest challenge was distributions with a high ratio of kurtosis to skewness. We discuss how these cases might be handled, and we highlight some of the broader issues associated with transformation. Copyright © 2016 John Wiley & Sons, Ltd.

This review examined the general level of effectiveness that can be drawn from a systematic review of the literature for dietary supplements based on the following three premises: 1) ability to elicit body compositional changes; 2) ability to elicit changes in musculoskeletal performance; and 3) ability to elicit improvements in cardiovascular health and endurance. Based on the culmination of review of available studies, to date there is limited support to many of the purported benefits that have been ascribed to a host of dietary supplements.

Aims PKN1 is a stress-responsive protein kinase acting downstream of small GTP-binding proteins of the Rho/Rac family. The aim was to determine its role in endogenous cardioprotection. Methods and results Hearts from PKN1 knockout (KO) or wild type (WT) littermate control mice were perfused in Langendorff mode and subjected to global ischaemia and reperfusion (I/R). Myocardial infarct size was doubled in PKN1 KO hearts compared to WT hearts. PKN1 was basally phosphorylated on the activation loop Thr778 PDK1 target site which was unchanged during I/R. However, phosphorylation of p42/p44-MAPK was decreased in KO hearts at baseline and during I/R. In cultured neonatal rat ventricular cardiomyocytes (NRVM) and NRVM transduced with kinase dead (KD) PKN1 K644R mutant subjected to simulated ischaemia/reperfusion (sI/R), PhosTag® gel analysis showed net dephosphorylation of PKN1 during sI and early R despite Thr778 phosphorylation. siRNA knockdown of PKN1 in NRVM significantly decreased cell survival and increased cell injury by sI/R which was reversed by WT- or KD-PKN1 expression. Confocal immunofluorescence analysis of PKN1 in NRVM showed increased localization to the sarcoplasmic reticulum (SR) during sI. GC-MS/MS and immunoblot analysis of PKN1 immunoprecipitates following sI/R confirmed interaction with CamKIIδ. Co-translocation of PKN1 and CamKIIδ to the SR/membrane fraction during sI correlated with phospholamban (PLB) Thr17 phosphorylation. siRNA knockdown of PKN1 in NRVM resulted in increased basal CamKIIδ activation and increased PLB Thr17 phosphorylation only during sI. In vivo PLB Thr17 phosphorylation, Sarco-Endoplasmic Reticulum Ca2+ ATPase (SERCA2) expression and Junctophilin-2 (Jph2) expression were also basally increased in PKN1 KO hearts. Furthermore, in vivo P-V loop analysis of the beat-to-beat relationship between rate of LV pressure development or relaxation and end diastolic P (EDP) showed mild but significant systolic and diastolic dysfunction with preserved ejection fraction in PKN1 KO hearts. Conclusion Loss of PKN1 in vivo significantly reduces endogenous cardioprotection and increases myocardial infarct size following I/R injury. Cardioprotection by PKN1 is associated with reduced CamKIIδ-dependent PLB Thr17 phosphorylation at the SR and therefore may stabilize the coupling of SR Ca2+ handling and contractile function, independent of its kinase activity.

This investigation assessed differences between the response of men and women with knee osteoarthritis to superficial heat, cold, or contrast therapy applied with a water-circulating system or a standard heating pad, and rest. We further analyzed data from a previous study to better understand the influence of gender on the response to treatment based on Knee Injury and Osteoarthritis Outcome Score (KOOS) subscales and a visual analog pain scale (VAS). Using a within-subject, randomized order design, 34 patients received each treatment in 1-week blocks. A KOOS questionnaire and VAS were completed at baseline and twice each week. Women were more likely to report clinically meaningful improvement in pain and symptoms on the KOOS with the use of heat, cold, and a heating pad. There were no significant differences in response to treatment between men and women for the function-daily living and quality of life subscales or percent pain reduction on the VAS. Men and women reported improved quality of life with intervention. Women are more likely to report clinically meaningful improvement in pain and symptoms associated with knee OA following the use of superficial heat, cold, or a heating pad than men.

The purpose of this study is to perform a match comparison of 3 different exercise programs: traditional continuous endurance training (ET); mixed-intensity interval ET (MI-ET); and circuit-interval resistance training (CRT) programs, to determine which of the 3 programs provides greater benefit of exercise in individuals who are overweight. This benefit of training is measured in Caloric expenditure per minute of exercise (kcalxmin), along with acute cardiovascular responses (average and maximal heart rate [HR], bxmin) and time of training spent within a favorable HR training zone for the exerciser. Thirteen (13) individuals, 7 men and 6 women, average of 35 +/- 2.3 years of age, who are overweight, average body weight of 79.8 +/- 5.1 kg with a body mass index of 35 +/- 1, were recruited from a local fitness center and were then randomly assigned to an order to complete 1 session of each of the 3 modes of exercise. There was no difference between program groups (MI-ET, CRT, and ET programs) for average HR response, p0.05; however, the individuals while performing the MI-ET program spent a greater percent of training time within a favorable training zone than the CRT or ET programs (p0.01). Additionally, the MI-ET and CRT programs produced greater Caloric expenditure (kcalxmin) than the ET program (p0.01) with no statistical difference between the MI-ET and CRT programs (p0.05). Although the CRT produces the greatest overall Caloric expenditure, the MI-ET program produces measures that provided a significantly greater benefit of exercise for the 3 programs of interest.

Background Chronic fatigue syndrome is a common condition characterized by severe fatigue with post-exertional malaise, impaired cognitive ability, poor sleep quality, muscle pain, multi-joint pain, tender lymph nodes, sore throat or headache. Its defining symptom, fatigue is common to several diseases. Areas of agreement Research has established a broad picture of impairment across autonomic, endocrine and inflammatory systems though progress seems to have reached an impasse. Areas of controversy The absence of a clear consensus view of the pathophysiology of fatigue suggests the need to switch from a focus on abnormalities in one system to an experimental and clinical approach which integrates findings across multiple systems and their constituent parts and to consider multiple environmental factors. Growing points We discuss this with reference to three key factors, non-determinism, non-reductionism and self-organization and suggest that an approach based on these principles may afford a coherent explanatory framework for much of the observed phenomena in fatigue and offers promising avenues for future research. Areas timely for developing research By adopting this approach, the field can examine issues regarding aetiopathogenesis and treatment, with relevance for future research and clinical practice.

Objectives: Previous studies have consistently shown increased rates of childhood adversity in chronic fatigue syndrome (CFS). However, such aetiopathogenic studies of CFS are potentially confounded by co-morbidity and misdiagnosis particularly with depression. We used a modelling approach with existing data and data generated in our examination of the rates of childhood adversity in a sample of CFS patients who had no lifetime history of depression. Methods: The childhood trauma questionnaire (CTQ) was completed by a sample of 52 participants and 19 controls with chronic fatigue syndrome who did not meet criteria for a psychiatric disorder (confirmed using the Structured Clinical Interview for DSM-IV). Subsequently, Mediation Analysis (Baye’s Rules) was used to establish the risk childhood adversity poses for CFS with and without depression. Results: In a cohort of CFS patients with depression robustly excluded, CTQ scores were markedly lower than in all previous studies and, in contrast to these previous studies, not increased compared with healthy controls. Post-hoc analysis showed that CTQ scores correlated with the number of depressive symptoms during the lifetime worst period of low mood. The probability of developing CFS given a history of childhood trauma was shown to be 4%, a two-fold increased risk compared to the general population. However, much of this risk is mediated by the concomitant development of major depression. Discussion: The data suggests that previous studies showing a relationship between childhood adversity and CFS may be mediated by depression

Neuroendocrine data are typically positively skewed and rarely conform to the expectations of a Gaussian distribution. This can be a problem when attempting to analyse results within the framework of the general linear model, which relies on assumptions that residuals in the data are normally distributed. One frequently used method for handling violations of this assumption is to transform variables to bring residuals into closer alignment with assumptions (as residuals are not directly manipulated). This is often attempted through ad hoc traditional transformations such as square root, log and inverse. However, Box and Cox (BoxCox, ) observed that these are all special cases of power transformations and proposed a more flexible method of transformation for researchers to optimise alignment with assumptions. The goal of this paper is to demonstrate the benefits of the infinitely flexible Box-Cox transformation on neuroendocrine data using syntax in spss. When applied to positively skewed data typical of neuroendocrine data, the majority (~2/3) of cases were brought into strict alignment with Gaussian distribution (i.e. a non-significant Shapiro-Wilks test). Those unable to meet this challenge showed substantial improvement in distributional properties. The biggest challenge was distributions with a high ratio of kurtosis to skewness. We discuss how these cases might be handled, and we highlight some of the broader issues associated with transformation. Copyright © 2016 John WileySons, Ltd.

The purpose of this paper is to explore various traffic modeling aspects and theories that may overcome some of the limitations in existing microscopic simulation models. A multiregime microscopic traffic simulation approach has been formulated featuring realistic and comprehensive carfollowing and lane-changing logic. A prototype implementation of the multiregime approach was developed in C++ and extensively tested. The multiregime simulation results demonstrate the efficiency and validity of the proposed models for a broad range of traffic scenarios. The test and validation results indicate that the model and program outperformed traditional methods and other existing traffic simulation programs. The validity and efficiency of the model is attributed to the fact that the regimes were added to the model incrementally to reflect increasing agreement with real-world traffic flow. The techniques and corresponding models will be used to improve existing microscopic traffic simulation models and programs.

Michael F Joseph1, Craig R Denegar1, Elaine Horn1, Bradley MacDougall1, Michael Rahl1, Jessica Sheehan1, Thomas Trojian2, Jeffery M Anderson1, James E Clark1, William J Kraemer11Department of Kinesiology, 2Department of Sports Medicine, University of Connecticut, Storrs, CT, USAAbstract: Lower extremity mechanics during landing have been linked to traumatic and nontraumatic knee injuries, particularly in women’s athletics. The effects of efforts to mitigate these risks have not been fully elucidated. We previously reported that a 5° medial wedge reduced ankle eversion and knee valgus. In the present report we further investigated the effect of a 5° medial wedge inserted in the shoes of female athletes on frontal plane hip motion, as well as ankle, knee, hip, and trunk saggital plane motion during a jump landing task. Kinematic data were obtained from 10 intercollegiate female athletes during jump landings from a 31 cm platform with and without a 5° medial wedge. Hip adduction was reduced 1.98° (95% CI 0.97–2.99°) by the medial wedge but saggital plane motions were unaffected. A 5° medial wedge reduces frontal plane motion and takes the knee away from a position associated with anterior cruciate ligament injury and patellofemoral pain syndrome. Although frontal plane motion was not captured it is unlikely to have increased in a bilateral landing task. Thus, it is likely that greater muscle forces were generated in these highly trained athletes to dissipate ground reaction forces when a medial wedge was in place. Additional investigation in younger and lesser trained athletes is warranted to assess the impact of orthotic devices on knee joint mechanics.Keywords: jump landing, foot orthotic, lower extremity kinematics, knee biomechanics, knee injury

Fifty-three primary uncemented custom-molded Identifit (Depuy, Warsaw, IN) hip arthroplasties were evaluated prospectively at a mean follow-up period of 30 months. The custom technique provided the capability to reproduce the unique femoral offset, version, and height in each hip and to achieve high percentages of femoral canal fill. Surgical time for unilateral cases was a mean 153 minutes. Clinical results, however, were disappointing. Nine hips (17%) required stem revision for persistent thigh pain and limping. Of the remaining 44 hips, the mean Harris hip score was 83, and 20% experienced moderate to severe thigh pain and 50% had a limp. Radiographically, 65% of the stems had subsided and 27% had migrated into valgus. Survivorship analysis predicted an 80% stem survival rate at 43 months. A precise fit and fill of the femoral canal is not in itself sufficient for femoral implant stability in total hip arthroplasty surgery.

Microconductance catheters have been successfully applied to measure left ventricular (LV) function in the mouse to assess cardiac or pharmacological interventions for a number of years. New complex admittance methods produce an estimate of the parallel admittance of cardiac muscle that can be used to correct the measurement in real time. This contrasts with existing conductance technologies that require in vivo calibration using a bolus of hypertonic saline. Here, we report the application of this emerging technology in the context of myocardial infarction and LV remodelling. Using a combination of high-resolution ultrasound and LV conductance catheters, we compared measures of LV function using an admittance system and a traditional conductance-derived pressure-volume (PV) system. We subjected C57BL/6 mice to focal myocardial ischaemia-reperfusion by transient ligation of the left anterior descending coronary artery and assessed cardiac function with different systems to determine the reliability and accuracy of these methods to distinguish between normal and dysfunctional ventricle. We demonstrate that the admittance PV system, in our hands, provides a straightforward solution for assessing LV function in mice. Using this technique in combination with other established methods, we measured LV dysfunction following coronary artery occlusion and reperfusion, which can be ameliorated using a known preconditioning agent (CORM-3), and found that functional read-outs are representative of other methods. We have found that, especially in diseased tissue, LV pressure-volume loops derived from complex admittance provide a reproducible and reliable method of determining LV function without the need for technically challenging calibration. Our data suggest that admittance records accurate/physiological LV cavity volumes when compared with other invasive methods in the same animal. This emerging technology is both effective and reproducible for measuring LV function and dysfunction in the mouse, without the need for complicated interventions to calibrate the measurements or training in a new technology. This may mark the way towards a fast and accurate assessment of murine cardiac function in normal animals and disease models.

Over the last half century there has been an epidemic of diminished health status induced by what seems as a concurrent rise in a population of individuals that are overfat. During the past few decades, the use of exercise has become a staple in the prevention and treatment options for the retarding the development of health issues pertaining to individuals who are overweight, overfatness or experience obesity. However, there are few studies and reviews look at the global issues surrounding the metabolic and hormone consequences of overfatness and the interaction of exercise with adiposity in humans developing the health status for the individual. This review offers an insight into our current understanding of health issues pertaining to metabolic and hormonal disruption related to overfatness and the treatment effect that exercise, especially resistance exercise, can have on impacting the health status, and overall well-being, for individuals who are overfat, regardless of body compositional changes leading toward a lessening of diseased state, and eventually a return to a normal health status for the individual.

“No Migration” Petitions must be submitted by operators of Class I hazardous disposal wells to apply for an exemption from the federal land ban restrictions on the disposal of hazardous waste. In many Class I disposal well operations, the injectate density can vary daily and usually has a different density than the native formation brine. The influence of the density contrast on the fluid potential must be included in a “No Migration” Petition modeling demonstration. After the model wells (s) is shut-in, the density contrast results in a net updip (lower density injectate) or downdip (higher density injectate) component of flow near the center of mass of the calculated plume (neglecting regional flow). In many cases, two model runs are required: one using the lowest anticipated injectate density and one using the highest anticipated injectate density for the entire modeled operational period. This was intended to provide adequate plume delineation over the injectate density range and implies that buoyancy effects on the plume position are not related to the average density. Three separate cases of a two-dimensional generic numerical model were used to examine buoyancy effects using constant and variable injectate density input values. Case 1 used a random selection of the daily variation about the mean density, and case 2 used correlated daily injectate densities over a five day period. The model calculated concentrations from cases 1 and 2 were compared to the results from a third case that used the mean density input value for the entire operational period. The calculated plume extent for all three cases is virtually identical for simulation times up to 10,000 years. The modeling results demonstrate that using a long-term average injectate density in “No Migration” Petition modeling rather than the range of extreme values may be justifiable by operators of Class I injection well facilities.

A factor analysis of the Survey on Economic Attitudes suggests an underlying set of seven orthogonal attitude variables. The cognitive learning effect of these variables is contrasted with results from a change score model of learning that did not include these attitude measures.

Osteoarthritis (OA) of the knee is a common and progressive condition. Michael et al1 reported that 6% of adults suffer from clinically significant knee OA with the prevalence increasing with each decade of life. Lawrence et al2 provided a summary of population based studies which revealed estimates of symptomatic and radiographically confirmed knee OA as high as 16.7%3 for those 45 years and older, with women more affected than men.2 OA results in pain and recurrent swelling and is associated with progressive functional limitations and disability.2 Multiple treatment options are available for patients with OA of the knee including the use of superficial heat or cold, transcutaneous electrical nerve stimulation (TENS), oral medications, injection of hyaluronic acid or a corticosteroid, or ultimately knee joint replacement surgery.4–6 Unfortunately, knee OA is a progressive disease and not all patients are good candidates for all interventions. Moreover, there are risks and side effects associated with medications and surgery that are not associated with some remedies, such as superficial heat or cold applications.6,7 Furthermore, not all treatment options meet with the same results, supporting individualized patient management approaches. The benefits of others such as injections of hyaluronic acid or a corticosteroid do not last indefinitely and must be repeated.8,9 The use of lower risk, lower cost interventions that are effective in helping patients manage chronic conditions including knee OA, warrant further examination and attention when discussing treatment options or recommending a plan of care. The periodic application of superficial heat or cold is a relatively safe and low cost treatment that can be recommended in isolation or in combination with other treatments for patients with knee OA.10 Contrast therapy involving intervals of heat and cold application within a treatment session offers yet another option in the management of many different musculoskeletal conditions, including knee OA. Few studies are available to demonstrate if either superficial heat, cold, or contrast therapies are of greater benefit.11 Despite limited understanding of the response to heat, cold, or contrast modalities in the management of knee OA, the application of superficial heat or cold is very common, often self-initiated, and is considered a component of a “first-line” intervention in the management of knee pain in older adults.4,12 Porcheret et al12 reported that of 201 older patients with knee pain surveyed, 84% reported applying superficial heat or cold, and most reported this treatment as a self-initiated intervention. Additionally, Cetin et al4 reported that the use of superficial heat or cold in conjunction with diathermy, TENS or ultrasound led to varying levels of symptom relief and functional improvements in patients with knee OA. Health care providers are often asked whether heat or cold is better, and how these modalities should be used outside of clinical settings for treatment of knee OA.11 Unfortunately, as previously noted, there are no clear answers or recommendations for patients to follow, hence anecdotal recommendations are often based on personal experiences, patient preferences, and previously established clinical training and education.10–15 Studying the response to thermal modalities is complicated by the fact that it is not possible to blind subjects or providers to the intervention. Moreover, clinical observations show many patients have experiences with heat and cold applications and express preferences based on these experiences. The first purpose of this Phase I study (subjects were randomized to order but not to a particular treatment with primary focus on treatment preference) was to investigate the preferences of patients with knee OA using a single device that is able to provide multiple treatment options with an identical method of application. Other factors may also need to be considered in recommending treatments. Impairments of the hand and loss of mobility in the lower extremities may impede an individual’s ability to self-apply superficial heat and cold around a peripheral joint. For example, securing an ice pack can be difficult for some patients. Furthermore, wrapping an electric heating pad in place poses risk of burns, especially if peripheral sensation or circulation is compromised. Several commercially available warm and cold-water circulating units offer a means of surrounding a joint with a garment through which temperature controlled water circulates. These garments are wrapped around the joint and held in place with Velcro™ closures. These garments may offer a safer and more convenient means of applying cold or heat. The second purpose of this investigation was to assess the preferences of patients toward a given treatment option provided by a wrap-around system when compared to use of a standard electric heating pad. A preferred treatment may or may not yield a better outcome. The third purpose of this investigation was to assess self-reports of patients with level II or greater OA16 for pain, symptoms, function in daily living (FDL) and recreation, and quality of life (QOL), following 5 days of twice daily superficial heat, cold or contrast therapy applied with a wrap-around water circulating device, twice daily use of a standard heating pad, or twice daily rest for 20 minutes.

Growth hormone (hGH) presents pleiotropic effects in many tissues encompassing a diverse range of physiological actions. Its complexity as a family of hormones with different isoforms and different somatotroph molecular functions continues to challenge the status quo of our understanding of its release, function, and signaling. Owing to the fact that the majority of the literature has viewed hGH from the perspective of the primary 22 kD monomer, further investigation is needed as to the influence and biological activity of other aggregate and splice variant isoforms that are released into circulation. Its role over the life span and with supplementation yields equivocal results with more study needed. Testing for the use of hGH has progressed, and the first positive test was recently documented. Understanding of pituitary function and physiology will remain complex until the use of a broader range of analytical techniques, including assays, becomes mainstream.

The purpose of this study is to examine improvements in cardiorespiratory fitness (VO(2)) after the use of a mixed-intensity interval endurance-training (MI-ET) program in female soccer players, to validate the MI-ET program as an appropriate training regimen to improve cardiorespiratory fitness (VO(2)) in soccer players. 32 female soccer players (average 18.66 +/- 0.31 years) were recruited from a group of currently conditioning local U-19 and college soccer teams and randomly assigned to participate in an 8-week periodized training program that involved either the MI-ET program or the continuation of a current endurance-training (ET) program. Analysis of variance indicates no differences in VO(2) values within the group of athletes before participating in the exercise program. After the 8 weeks of training, the MI-ET group of athletes had significantly greater average VO(2) values (62.13 +/- 0.96 ml O2.kg.min vs. 57.27 +/- 1.59 ml O2.kg.min), p = 0.015, along with a greater group average of change in VO(2) (12.44 +/- 0.92 ml O2.kg.min vs. 7.72 +/- 0.99 ml O2.kg.min), p < 0.001. The MI-ET program is shown to be a valid means to improve aerobic fitness as indicated by the MI-ET group exhibiting significantly greater VO(2) measures after training.

Ischemic heart disease complicated by coronary artery occlusion causes myocardial infarction (MI), which is the major cause of morbidity and mortality in humans (http://www.who.int/cardiovascular_diseases/resources/atlas/en/index.html). After MI the human heart has an impaired capacity to regenerate and, despite the high prevalence of cardiovascular disease worldwide, there is currently only limited insight into how to stimulate repair of the injured adult heart from its component parts. Efficient cardiac regeneration requires the replacement of lost cardiomyocytes, formation of new coronary blood vessels, and appropriate modulation of inflammation to prevent maladaptive remodeling, fibrosis/scarring, and consequent cardiac dysfunction. Here we show that thymosin beta4 (Tbeta4) promotes new vasculature in both the intact and injured mammalian heart. We demonstrate that limited EPDC-derived endothelial-restricted neovascularization constitutes suboptimal "endogenous repair," following injury, which is significantly augmented by Tbeta4 to increase and stabilize the vascular plexus via collateral vessel growth. As such, we identify Tbeta4 as a facilitator of cardiac neovascularization and highlight adult EPDCs as resident progenitors which, when instructed by Tbeta4, have the capacity to sustain the myocardium after ischemic damage.

Computers have been a useful engineering tool for several years. As computers have become more inexpensive and easier to use, engineers have increased their use of them. Associated with increased use of computers are a number of management problems. These problems are related to the relationships between individuals, individuals and machines, and organizations. These problems really relate to the management of work, rather than the technical performance of work. This paper describes some of the management problems that have been encountered, as well as ways to prevent such problems for other users. Management problems have been classified into primary and secondary types for the purpose of suggesting solutions. It is the intent of the paper to make future users of computer programs aware of the problems so that their particular applications may be successful.

The first reported case of bilateral renal hemangiopericytoma ispresented. The 19 previous renal hemangiopericytomas that have been reported in the world literature are reviewed. This lesion has afflicted patients ranging in age from sixteen to sixty-eight years (mean 41 years) with an equal sex distribution. Mortality from hemangiopericytoma of the kidney has been 50 percent, and the primary mode of therapy remains surgical.

Glycogen synthase kinase-3 (GSK-3) is implicated as an important signalling mediator in normal developmental myocardial growth and adverse hypertrophic remodelling. Upstream phosphorylation of isoform specific N-terminal serine residues - ser21(GSK-3α) and ser9(GSK-3β), respectively - inhibits kinase activity. Opposing effects of the two isoforms have recently been described in response to hypertrophic stimuli, but little is known of the overall effect of dual-isoform manipulation. We set out to characterise baseline and isoproterenol (ISO) stimulated phenotypes of mice with inactivation-resistant GSK-3αβ knockin (KI) alleles, in which ser21/9 are converted to non-phosphorylatable alanine. Between 5–15 weeks there was a non-significant trend towards higher heart weight (HW): body weight (BW) ratios in KI mice versus wild type (WT) mice. Mean left ventricular wall thickness (LVWT) at the level of the papillary muscle was comparable between genotypes (1.3±0.2mm vs 1.6±0.2mm, ns, n=8). 8–10 week old weight-matched mice received 2 weeks subcutaneous ISO (30mg/kg/d) or control saline (Con) infusions. WT hearts hypertrophied with ISO (LVWT 1.9±0.1mm vs 1.3±0.2mm Con, n=8; HW:BW ratio 6.7±0.6 vs 5.4±0.4 Con, n=10, both p< 0.05), but KI mice did not (1.4±0.1mm vs 1.6±0.2mm KI Con; HW:BW 6.2±1.0 vs 6.1±0.6 KI Con, respectively, both ns). Hypertrophy in the WT hearts was associated with reduced LV ejection fraction (41±9% vs 63±5% Con, n=6, p< 0.05) and greater interstitial fibrosis (2.1±0.5% vs 0.8±0.6%, n=6, p< 0.05). These were both attenuated in the KI mice subjected to ISO (70±13% vs 64±11% Con, and 1.3±0.7% vs 0.8±0.3% Con, respectively, both ns). GSK-3 inhibition with daily intraperitoneal 6-bromoindirubin-3′-oxime restored hypertrophic sensitivity to ISO in the KI mice (LVWT 1.8±0.2mm; HW:BW 7.3±0.5, p< 0.05 for both groups vs KI + ISO alone) but had no effect in the absence of hypertrophic stimulus (1.4±0.2mm and 5.4±0.7, respectively, for KI + Con + Bio, ns vs KI + Con alone). In conclusion, inactivation-resistant GSK-3αβ dual isoform expression does not affect age-related (eutrophic) myocardial growth in the mouse. However, it protects against pathological growth, maintaining cardiac function and attenuating interstitial fibrosis.

Publisher Summary Disposal of liquids into underground formations through injection wells was started in 1930 by the U. S. petroleum industry, which as a common practice, disposed of produced brine in this manner. Underground injection is the disposal of liquid waste material into isolated geologic strata, placing the wastes in portions of the earth's crust that are free from the usual effects of the hydrologic cycle. Enactment of the Safe Drinking Water Act (SDWA) in 1974 ratified the Environmental Protection Agency's (EPA's) underground injection policy position and required the Agency to promulgate minimum injection well requirements of state programs to prevent endangerment of underground sources of drinking water (USDWs). In 1984, the Hazardous and Solid Waste Amendments (HSWA) prohibited land disposal of hazardous waste, including underground injection, unless the EPA could determine that the disposal would not adversely affect human health and the environment. Since 1980, with the implementation of the underground injection control (UIC) program of the SDWA, no cases of USDW contamination have occurred, due to stringent siting, construction, operation, and testing requirements for Class I hazardous and nonhazardous wells.

Publisher Summary This chapter explains that the rock mass near the dissolution cavities at Louisville was stable against collapse and remained so for the duration of injection operations and presents the test comparing stresses for various orientations of a test plane to the strength of rock samples near a 250 ft radius cavity. The solid straight line emerging from the origin is the locus of the normal stress–shear stress points that would exist in the absence of the cavity. The failure envelope, based on the measurements quoted above, intersects the shear stress axis at about 4800 psi, and slopes upward to the right. The failure envelope is well above the spread of calculated stress points in this case. Anticipated injection operations could lead to a cavity of roughly twice the size of the present-day cavity. The localized stresses in the vicinity of the solution cavities at Louisville are predicted. This perturbation of the preexisting stress field is insufficient to cause failure of the rock mass. Thus, the rock mass undergoes elastic deformation, and the calculated values are much less than ambient deformations due to other causes.

1 Carbon monoxide (CO), one of the end products of heme catabolism by heme oxygenase, possesses antihypertensive and vasodilatory characteristics. We have recently discovered that certain transition metal carbonyls are capable of releasing CO in biological fluids and modulate physiological functions via the delivery of CO. Because the initial compounds identified were not water soluble, we have synthesized new CO-releasing molecules that are chemically modified to allow solubility in water. The aim of this study was to assess the vasoactive properties of tricarbonylchloro(glycinato)ruthenium(II) (CORM-3) in vitro and in vivo. 2 CORM-3 produced a concentration-dependent relaxation in vessels precontracted with phenylephrine, exerting significant vasodilatation starting at concentrations of 25-50 microm. Inactive CORM-3, which does not release CO, did not affect vascular tone. 3 Blockers of ATP-dependent potassium channels (glibenclamide) or guanylate cyclase activity (ODQ) considerably reduced CORM-3-dependent relaxation, confirming that potassium channels activation and cGMP partly mediate the vasoactive properties of CO. In fact, increased levels of cGMP were detected in aortas following CORM-3 stimulation. 4 The in vitro and in vivo vasorelaxant activities of CORM-3 were further enhanced in the presence of YC-1, a benzylindazole derivative which is known to sensitize guanylate cyclase to activation by CO. Interestingly, inhibiting nitric oxide production or removing the endothelium significantly decreased vasodilatation by CORM-3, suggesting that factors produced by the endothelium influence CORM-3 vascular activities. 5 These results, together with our previous findings on the cardioprotective functions of CORM-3, indicate that this molecule is an excellent prototype of water-soluble CO carriers for studying the pharmacological and biological features of CO.

Nash MS, Jacobs PL, Woods JM, Clark JE, Pray TA, Pumarejo AE. A comparison of 2 circuit exercise training techniques for eliciting matched metabolic responses in persons with paraplegia. Arch Phys Med Rehabil 2002;83:201-9. Objective: To test whether acute metabolic (VO 2 ), chronotropic (heart rate), and perceptual (rating of perceived exertion; RPE) responses to exercise by persons with paraplegia differ when the exercise is on a multistation isoinertial exercise system (MultiGym) or on a customized system of Thera-Band® resistance bands (ElasticGym). Design: Within-subjects comparison of 2 treatments. Setting: Academic medical center. Participants: Sixteen men and 1 woman with complete paraplegia (T4-L1), as defined by the American Spinal Injury Association. Interventions: A circuit resistance training (CRT) program for persons with paraplegia was adapted to both a MultiGym and a customized ElasticGym. Exercises used for training and testing used 6 resistance maneuvers at 50% of the 1-repetition maximum (1-RM), with interposed rapid arm spinning. Subjects were habituated to both conditions for 2 weeks before testing on randomized nonconsecutive days. Main Outcome Measures: VO 2 (L/min) was measured by portable spirometry, heart rate (beats/min) by a chest strap monitor, and RPE by the Borg Scale of Perceived Exertion (6-20). Results: No significant effects of test condition on average VO 2 or heart rate were observed, with differences between conditions reflecting only.08L/min and 6.4 beats/min, respectively. Average RPE was significantly higher in testing under the ElasticGym condition ( P Conclusions: CRT on a customized ElasticGym system elicited acute metabolic and chronotropic responses that did not differ from responses to exercise on a MultiGym, though RPE was greater with the ElasticGym. © 2002 by the American Congress of Rehabilitation Medicine and the American Academy of Physical Medicine and Rehabilitation

Traffic congestion has historically been regarded as a problem confined to major metropolitan areas. Over the years, the traffic problems that existed in densely developed urban areas began creeping into the suburbs as the work force migrated away from the traditional center city work pattern. Modem business operates at a feverish pace and is more mobile in nature, automobile technology advances have allowed more people to drive, and the commuting public has caused traffic congestion problems to appear even in small towns. Simply adding pavement to mitigate the traffic problems is neither adequate nor feasible. The Intelligent Transportation Systems (ITS) initiative was invoked by congress in 1991 to advance our traffic control systems by fostering development of Advanced Traffic Management Systems (ATMS). These technologies are designed to help move the motoring public more efficiently over the existing transportation system. Computer simulation has proved to be a vital adjunct to traditional traffic engineering analysis methods in hlly understanding the dynamics of traffic movement and control operations,. These simulation tools are critical in the development and evaluation of these new ideas, algorithms, and traffic control systems. This paper presents three case studies illustrating the importance and positive impacts of

The development of a computer simulation model to approximate the interactions of those traffic elements present at a signalized intersection is presented. The simulation model is designed as a tool for the engineer or analyst to predict the behavior of a signalized intersection under different operational conditions. GASP IV is the simulation language used in this study. This language is FORTRAN based and can be easily implemented on the computing systems of different manufacturers. By varying different parameters (logo, geometrics, movement percentages, traffic signal information, volumes, phasing, etc.) while holding others constant, the impact of design changes were studied. Both exclusive and no exclusive left-turn phase signal operation were investigated and the simulation output indicates reasonable results. The engineer could use this simulation model in the integral part of making traffic operation decisions.