Hemodynamic and metabolic responses to moderate and vigorous cycle ergometry in men with transtibial amputation

Adults with amputation face barriers to an active lifestyle which attenuates cardiorespiratory fitness. Prior studies in amputees typically involve treadmill walking or arm ergometry, yet physiological responses to leg cycling are less understood. PURPOSE: To assess hemodynamic and metabolic responses to moderate and vigorous cycle ergometry in men with transtibial amputation (TTA), with broader application towards exercise programming. METHODS: Using a randomized within-subjects crossover design, five men with unilateral TTA (age = 39 ± 15 yr) and six able-bodied controls (CON) (age = 31 ± 11 yr) performed two 20 min bouts of cycling differing in intensity.Cardiac output (CO), heart rate (HR), stroke volume (SV), and oxygen consumption (VO2) were measured during moderate intensity continuous exercise (MICE) and high intensity interval exercise (HIIE) using thoracic impedance and indirect calorimetry. RESULTS: In response to MICE and HIIE, HR and VO2 were similar (p \u3e 0.05) between groups. Stroke volume and CO were higher (p \u3c 0.05) in CON which was attributed to their higher body mass. In men with TTA, HIIE elicited peak HR = 88 %HRmax and substantial blood lactate accumulation, representing vigorous exercise intensity. CONCLUSION: Men with TTA show similar responses to MICE and HIIE versus CON.These results provide important insight for developing exercise programs for adults with TTA, and based on similar acute responses versus CON, it appears that moderate and vigorous physical activity recommendations designed for implementation in non-amputees can be applied to men with transtibial amputation

Comparing Physiological Responses During Rowing High Intensity Interval Training (HIIT) versus High Intensity Functional Training (HIFT)

High intensity interval training (HIIT) improves cardiorespiratory fitness, glycemic control, and body composition, yet the majority of studies used cycling which employs a smaller muscle mass. Less data have examined the acute response to whole-body HIIT. PURPOSE: To compare physiological responses between HIIT rowing and high intensity functional training (HIFT). METHODS: Healthy, non-obese men and women (N=18, age=25±8 yr) who are physically active (PA=7±2hr, VO2max=39±8mL/kg/min) underwent graded exercise testing to determine VO₂max and peak power output (PPO) on the rowing ergometer. On two separate days, subjects performed a time-matched bout of HIFT or HIIT rowing. HIIFT required 6 ‘all-out’ sets of 10 push-ups, 10 jump squats, 20 mountain climbers, and 20 body-weight squats separated by 75 s recovery. HIIT rowing consisted of six 1min bouts at 85% PPO with 75 s of recovery. Gas exchange data, heart rate (HR), affective valence, and RPE were obtained during exercise. Blood lactate concentration (BLa) was measured at rest, bout 3, and 5, 10, and 15 min post-exercise. RESULTS: There were significant differences (p2 was higher (p=0.03) with HIIT rowing versus HIFT (1.88 ± 0.51 vs. 1.67 ± 0.35 L/min) as was total O2 (31±8 vs. 28±6L). GroupXtime interactions (pE, and RPE occurred, with higher values demonstrated to HIFT. CONCLUSION: HIFT elicited a higher peak HR, BLa, and RER, suggesting a higher peak cardiovascular stimulus and greater activation of glycolysis, likely due to greater recruitment of fast twitch fibers. Yet, HIIT rowing elicited higher energy expenditure and mean VO2 versus HIFT. The eccentric nature of HIFT may explain the blunted VO2 response, although more studies are needed to verify this result

HOOK-GRIP IMPROVES POWER CLEAN KINETICS AND KINEMATICS

The purpose of this study was to compare one repetition maximum (1RM), as well as biomechanical outputs across a range of loads (75-100%) in the power clean (PC) utilizing the hook grip (HG) or closed-grip (CG). Eleven well-trained males (PC 1RM=1.34xBW) with at least six months of HG experience volunteered. Following a familiarization session, PC 1RM testing with the HG and CG were completed in random order, 5-7 days apart on a force platform with linear position transducers and 2D motion capture. The HG condition resulted in greater PC 1RM (6.6%, ES=0.43), peak barbell velocity (2.9-5.2%, ES=0.41-0.70) and relative peak barbell power (5.7-15.1%, ES=0.32-0.71) at all submaximal loads compared to CG. No substantial differences were found in horizontal bar-path (ES=-0.27-0.32). The results of this study suggest that athletes who implement weightlifting movements in their physical preparation should adopt the HG

A comparison of phenotypic and WGS drug susceptibility testing in Mycobacterium tuberculosis isolates from the Republic of Korea

BACKGROUND: WGS has significant potential to help tackle the major public health problem of TB. The Republic of Korea has the third highest rates of TB of all Organisation for Economic Cooperation and Development countries but there has been very limited use of WGS in TB to date. OBJECTIVES: A retrospective comparison of Mycobacterium tuberculosis (MTB) clinical isolates from 2015 to 2017 from two centres in the Republic of Korea using WGS to compare phenotypic drug susceptibility testing (pDST) and WGS drug susceptibility predictions (WGS-DSP). METHODS: Fifty-seven MTB isolates had DNA extracted and were sequenced using the Illumina HiSeq platform. The WGS analysis was performed using bwa mem, bcftools and IQ-Tree; resistance markers were identified using TB profiler. Phenotypic susceptibilities were carried out at the Supranational TB reference laboratory (Korean Institute of Tuberculosis). RESULTS: For first-line antituberculous drugs concordance for rifampicin, isoniazid, pyrazinamide and ethambutol was 98.25%, 92.98%, 87.72% and 85.96%, respectively. The sensitivity of WGS-DSP compared with pDST for rifampicin, isoniazid, pyrazinamide and ethambutol was 97.30%, 92.11%, 78.95% and 95.65%, respectively. The specificity for these first-line antituberculous drugs was 100%, 94.74%, 92.11% and 79.41%, respectively. The sensitivity and specificity for second-line drugs ranged from 66.67% to 100%, and from 82.98% to 100%, respectively. CONCLUSIONS: This study confirms the potential role for WGS in drug susceptibility prediction, which would reduce turnaround times. However, further larger studies are needed to ensure current databases of drug resistance mutations are reflective of the TB present in the Republic of Korea

Prolonged enoxaparin therapy compared with standard-of-care antithrombotic therapy in opiate-treated patients undergoing primary percutaneous coronary intervention

A novel enoxaparin regimen consisting of intra-arterial bolus (0.75 mg/kg) followed by intravenous infusion (0.75 mg/kg/6 hours) has been developed as a possible solution to the delayed absorption of oral P2Y12 inhibitors in opiate-treated ST-elevation myocardial infarction (STEMI) patients undergoing primary angioplasty. We aimed to study the feasibility of this regimen as an alternative to standard-of-care treatment (SOC) with unfractionated heparin ± glycoprotein IIb/IIIa antagonist (GPI). One hundred opiate-treated patients presenting with STEMI and accepted for primary angioplasty were randomized (1:1) to either enoxaparin or SOC. Fifty patients were allocated enoxaparin (median age 61, 40% females) and 49 allocated SOC (median age 62, 22% females). One developed stroke before angiography and was withdrawn. One SOC patient had a gastrointestinal bleed resulting in 1 g drop in hemoglobin and early cessation of GPI infusion. Two enoxaparin patients had transient minor bleeding: one transient gingival bleed and one episode of coffee ground vomit with no hemoglobin drop or hemodynamic instability. Two SOC and no enoxaparin group patients had acute stent thrombosis. These preliminary data support further study of this novel 6-hour enoxaparin regimen in opiate-treated PPCI patients

Observations and Recommendations for the Calibration of Landsat 8 OLI and Sentinel 2 MSI for Improved Data Interoperability

Combining data from multiple sensors into a single seamless time series, also known as data interoperability, has the potential for unlocking new understanding of how the Earth functions as a system. However, our ability to produce these advanced data sets is hampered by the differences in design and function of the various optical remote-sensing satellite systems. A key factor is the impact that calibration of these instruments has on data interoperability. To address this issue, a workshop with a panel of experts was convened in conjunction with the Pecora 20 conference to focus on data interoperability between Landsat and the Sentinel 2 sensors. Four major areas of recommendation were the outcome of the workshop. The first was to improve communications between satellite agencies and the remote-sensing community. The second was to adopt a collections-based approach to processing the data. As expected, a third recommendation was to improve calibration methodologies in several specific areas. Lastly, and the most ambitious of the four, was to develop a comprehensive process for validating surface reflectance products produced from the data sets. Collectively, these recommendations have significant potential for improving satellite sensor calibration in a focused manner that can directly catalyze efforts to develop data that are closer to being seamlessly interoperable

GENCODE: producing a reference annotation for ENCODE

BACKGROUND: The GENCODE consortium was formed to identify and map all protein-coding genes within the ENCODE regions. This was achieved by a combination of initial manual annotation by the HAVANA team, experimental validation by the GENCODE consortium and a refinement of the annotation based on these experimental results. RESULTS: The GENCODE gene features are divided into eight different categories of which only the first two (known and novel coding sequence) are confidently predicted to be protein-coding genes. 5' rapid amplification of cDNA ends (RACE) and RT-PCR were used to experimentally verify the initial annotation. Of the 420 coding loci tested, 229 RACE products have been sequenced. They supported 5' extensions of 30 loci and new splice variants in 50 loci. In addition, 46 loci without evidence for a coding sequence were validated, consisting of 31 novel and 15 putative transcripts. We assessed the comprehensiveness of the GENCODE annotation by attempting to validate all the predicted exon boundaries outside the GENCODE annotation. Out of 1,215 tested in a subset of the ENCODE regions, 14 novel exon pairs were validated, only two of them in intergenic regions. CONCLUSION: In total, 487 loci, of which 434 are coding, have been annotated as part of the GENCODE reference set available from the UCSC browser. Comparison of GENCODE annotation with RefSeq and ENSEMBL show only 40% of GENCODE exons are contained within the two sets, which is a reflection of the high number of alternative splice forms with unique exons annotated. Over 50% of coding loci have been experimentally verified by 5' RACE for EGASP and the GENCODE collaboration is continuing to refine its annotation of 1% human genome with the aid of experimental validation

Phenotypic heterogeneity and genetic modification of P102L inherited prion disease in an international series

The largest kindred with inherited prion disease P102L, historically Gerstmann-Sträussler-Scheinker syndrome, originates from central England, with émigrés now resident in various parts of the English-speaking world. We have collected data from 84 patients in the large UK kindred and numerous small unrelated pedigrees to investigate phenotypic heterogeneity and modifying factors. This collection represents by far the largest series of P102L patients so far reported. Microsatellite and genealogical analyses of eight separate European kindreds support multiple distinct mutational events at a cytosine-phosphate diester-guanidine dinucleotide mutation hot spot. All of the smaller P102L kindreds were linked to polymorphic human prion protein gene codon 129M and were not connected by genealogy or microsatellite haplotype background to the large kindred or each other. While many present with classical Gerstmann-Sträussler-Scheinker syndrome, a slowly progressive cerebellar ataxia with later onset cognitive impairment, there is remarkable heterogeneity. A subset of patients present with prominent cognitive and psychiatric features and some have met diagnostic criteria for sporadic Creutzfeldt-Jakob disease. We show that polymorphic human prion protein gene codon 129 modifies age at onset: the earliest eight clinical onsets were all MM homozygotes and overall age at onset was 7 years earlier for MM compared with MV heterozygotes (P = 0.02). Unexpectedly, apolipoprotein E4 carriers have a delayed age of onset by 10 years (P = 0.02). We found a preponderance of female patients compared with males (54 females versus 30 males, P = 0.01), which probably relates to ascertainment bias. However, these modifiers had no impact on a semi-quantitative pathological phenotype in 10 autopsied patients. These data allow an appreciation of the range of clinical phenotype, modern imaging and molecular investigation and should inform genetic counselling of at-risk individuals, with the identification of two genetic modifiers

Functional genomics of abiotic environmental adaptation in lacertid lizards and other vertebrates

Understanding the genomic basis of adaptation to different abiotic environments is important in the context of climate change and resulting short-term environmental fluctuations. Using functional and comparative genomics approaches, we here investigated whether signatures of genomic adaptation to a set of environmental parameters are concentrated in specific subsets of genes and functions in lacertid lizards and other vertebrates. We first identify 200 genes with signatures of positive diversifying selection from transcriptomes of 24 species of lacertid lizards and demonstrate their involvement in physiological and morphological adaptations to climate. To understand how functionally similar these genes are to previously predicted candidate functions for climate adaptation and to compare them with other vertebrate species, we then performed a meta-analysis of 1,100 genes under selection obtained from -omics studies in vertebrate species adapted to different abiotic factors. We found that the vertebrate gene set formed a tightly connected interactome, which was to 23% enriched in previously predicted functions of adaptation to climate, and to a large part (18%) involved in organismal stress response. We found a much higher degree of identical genes being repeatedly selected among different animal groups (43.6%), and of functional similarity and post-translational modifications than expected by chance, and no clear functional division between genes used for ectotherm and endotherm physiological strategies. In total, 171 out of 200 genes of Lacertidae were part of this network. These results highlight an important role of a comparatively small set of genes and their functions in environmental adaptation and narrow the set of candidate pathways and markers to be used in future research on adaptation and stress response related to climate change

Advance Care Plans in UK care home residents: a service evaluation using a stepped wedge design

Introduction Advance care planning (ACP) in care homes has high acceptance, increases the proportion of residents dying in place and reduces hospital admissions in research. We investigated whether ACP had similar outcomes when introduced during real-world service implementation. Methods A service undertaking ACP in Lincoln, UK care homes was evaluated using routine data. Outcomes were proportion of care homes and residents participating in ACP; characteristics of residents choosing/declining ACP; and place of death for those with/without ACP. Hospital admissions were analysed using mixed-effects Poisson regression for number of admissions, and a mixed-effects negative binomial model for number of occupied hospital bed days. Results15/24 (63%) eligible homes supported the service, in which 404/508 (79.5%) participants chose ACP. Residents choosing ACP were older, frailer, more cognitively impaired and malnourished. 384/404 (95%) residents choosing ACP recorded their care home as their preferred place of death: 380/404 (94%) declined cardiopulmonary resuscitation. Among deceased residents, 219/248 (88%) and 33/49 (67%) with and without advance care plan respectively died in their care home (relative risk 1.35, 95%CI 1.1-1.6, p<0.001). Hospital admission rates and bed occupancy did not differ after implementation. Discussion 79.5% participants chose ACP. Those doing so were more likely to die at home. Many homes were unwilling or unable to support the service. Further research should consider how to enlist the support of these homes. Hospital admissions were not reduced and may not be an appropriate outcome metric for ACP in care homes