Features and frequency of use of electronic health records in primary care across 20 countries: a cross-sectional study.

OBJECTIVES: Variation exists in the capabilities of electronic healthcare records (EHRs) systems and the frequency of their use by primary care physicians (PCPs) from different settings. We aimed to examine the factors associated with everyday EHRs use by PCPs, characterise the EHRs features available to PCPs, and to identify the impact of practice settings on feature availability. STUDY DESIGN: Cross-sectional study. METHODS: PCPs from 20 countries completed cross-sectional online survey between June and September 2020. Responses which reported frequency of EHRs use were retained. Associations between everyday EHRs use and PCP and practice factors (country, urbanicity, and digital maturity) were explored using multivariable logistic regression analyses. The effect of practice factors on the variation in availability of ten EHRs features was estimated using Cramer's V. RESULTS: Responses from 1520 out of 1605 PCPs surveyed (94·7%) were retained. Everyday EHRs use was reported by 91·2% of PCPs. Everyday EHRs use was associated with PCPs working >28 h per week, having more years of experience using EHRs, country of employment, and higher digital maturity. EHRs features concerning entering, and retrieving data were available to most PCPs. Few PCPs reported having access to tools for 'interactive patient education' (37·3%) or 'home monitoring and self-testing of chronic conditions' (34·3%). Country of practice was associated with availability of all EHRs features (Cramer's V range: 0·2-0·6), particularly with availability of tools enabling patient EHRs access (Cramer's V: 0·6, P < 0.0001). Greater feature availability of EHRs features was observed with greater digital maturity. CONCLUSIONS: EHRs features intended for patient use were uncommon across countries and levels of digital maturity. Systems-level research is necessary to identify the country-specific barriers impeding the implementation of EHRs features in primary care, particularly of EHRs features enabling patient interaction with EHRs, to develop strategies to improve systems-wide EHRs use.

Increased short interval intracortical inhibition in participants with previous hamstring strain injury.

PURPOSE: Cortical mechanisms may contribute to weakness in participants with previous hamstring strain injury. This study aims to examine intra-cortical inhibition (SICI) and corticospinal excitability in previously injured participants. METHODS: In this cross-sectional study, TMS was used to examine SICI, silent period, silent period: MEP ratios and area under the stimulus response curve in the biceps femoris and medial hamstrings. Comparisons were made between participants with (n = 10) and without (n = 10) previous hamstring strain injury. Motor threshold and isometric knee flexor strength were also compared between participants and the relationship between strength and SICI in control and previously injured participants was examined. RESULTS: Isometric knee flexor strength was lower in previously injured limbs compared with control limbs (mean difference = - 41 Nm (- 26%) [95% CI = - 80 to - 2 Nm], p = 0.04, Cohen's d = - 1.27) and contralateral uninjured limbs (mean difference = - 23 Nm (- 17%), [95% CI = - 40 to - 6 Nm], p = 0.01, Cohen's d = - 0.57). Previously injured limbs exhibited smaller responses to paired pulse stimulation (i.e. greater levels of SICI) in the biceps femoris compared with control limbs (mean difference = - 19%, [95% CI = - 34 to - 5%], p = 0.007, Cohen's d = - 1.33). Isometric knee flexor strength was associated with the level of SICI recorded in the biceps femoris in previously injured participants (coefficient = 23 Nm [95% CI = 7-40 Nm], adjusted R2 = 0.31, p = 0.01). There were no differences in markers of corticospinal excitability between previously injured and control limbs (all p > 0.24, all Cohen's d < 0.40). CONCLUSION: Athletes with previous injury in the biceps femoris exhibit increased SICI in this muscle compared with control participants. Increased SICI is related to lower levels of hamstring strength, and rehabilitation programs targeting the removal of intra-cortical inhibition should be considered.

Justifying quarantine in preventing the spread of COVID-19 in healthcare.

BACKGROUND: The first COVID-19-positive patient was identified in Ireland on 29 February 2020 (Department of Health, Government of Ireland; https://www.gov.ie/en/pressrelease/2f75fd-statement-from-the-national-public-healthemergency-team-sat-29-feb/). Healthcare worker (HCW) quarantining became a core intervention for those identified as 'close contacts' to reduce onward transmission within the workplace to patients and colleagues. Whether a quarantining strategy could be justified at a time when there was an increased demand for the services of HCWs remained unknown. AIMS: To establish whether quarantining staff away from a healthcare setting during a pandemic is justified. METHODS: This retrospective study examined close contacts of COVID-19-positive index cases (both residents and HCWs) in a community hospital over a 4-week period from 1 to 28 April 2020. Close contacts were identified in accordance with national guidelines. Zones of the hospital were examined to determine the number of COVID-positive index cases and their close contacts. A cumulative result for the hospital was recorded. RESULTS: While outcomes varied over time, per zone and per HCW category, the overall conversion rate from close contact to an index case was 30%. CONCLUSIONS: This study vindicates the policy of quarantining close contact HCWs from their workplaces as they pose a significant threat to both their patients and fellow workers.

C57BL/6 mice are resistant to joint degeneration induced by whole-body vibration.

OBJECTIVE: Whole-body vibration (WBV) platforms are commercially available devices that are used clinically to treat numerous musculoskeletal conditions based on their reported ability to increase bone mineral density and muscle strength. Despite widespread use, there is an alarming lack of understanding of the direct effects of WBV on joint health. Previous work by our lab demonstrated that repeated exposure to WBV using protocols that model those used clinically, induces intervertebral disc (IVD) degeneration and osteoarthritis-like damage in the knee of skeletally mature, male mice of a single outbred strain (CD-1). The present study examined whether exposure to WBV induces similar deleterious effects in a genetically different strain of mouse (C57BL/6). DESIGN: Male 10-week-old C57BL/6 mice were exposed to vertical sinusoidal WBV for 30 min/day, 5 days/week, for 4 or 8 weeks using previously reported protocols (45 Hz, 0.3 g peak acceleration). Following WBV, joint tissues were examined using histological analysis and gene expression was quantified using real-time PCR (qPCR). RESULTS: Our analyses show a lack of WBV-induced degeneration in either the knee or IVDs of C57BL/6 mice exposed to WBV for 4 or 8 weeks, in direct contrast to the WBV-induced damage previously reported by our lab in CD-1 mice. CONCLUSIONS: Together with previous studies from our group, the present study demonstrates that the effects of WBV on joint tissues vary in a strain-specific manner. These findings highlight the need to examine genetic or physiological differences that may underlie susceptibility to the deleterious effects of WBV on joint tissues.

Pooled long-term outcomes from two randomized trials of axillary node sampling with axillary radiotherapy versus axillary node clearance in patients with operable node-positive breast cancer.

BACKGROUND: The aim was to determine long-term overall, breast cancer-specific and metastasis-free survival as well as axillary relapse rate from a pooled analysis of two randomized trials in women with operable breast cancer. These trials compared axillary node sampling (ANS), combined with axillary radiotherapy (AXRT) if the sampled nodes were involved, with axillary node clearance (ANC). METHODS: Data from two clinical trials at the Edinburgh Breast Unit that randomized patients between 1980 and 1995 were pooled. Long-term survival was analysed using Kaplan-Meier curves and Cox regression, with separate analyses for patients with node-positive (ANS + AXRT versus ANC) and node-negative (ANS versus ANC) disease. RESULTS: Of 855 women randomized, 799 were included in the present analysis after a median follow-up of 19·4 years. Some 301 patients (37·7 per cent) had node-positive disease. There was no evidence of a breast cancer survival advantage for ANS versus ANC in patients with node-negative disease (hazard ratio (HR) 0·88, 95 per cent c.i. 0·58 to 1·34; P = 0·557), or for ANS + AXRT versus ANC in those with node-positive breast cancer (HR 1·07, 0·77 to 1·50; P = 0·688). There was no metastasis-free survival advantage for ANS versus ANC in patients with node-negative tumours (HR 1·03, 0·70 to 1·51; P = 0·877), or ANS + AXRT versus ANC in those with node-positive disease (HR 1·03, 0·75 to 1·43; P = 0·847). Node-negative patients who underwent ANS had a higher risk of axillary recurrence than those who had ANC (HR 3·53, 1·29 to 9·63; P = 0·014). Similarly, among women with node-positive tumours, the risk of axillary recurrence was greater after ANS + AXRT than ANC (HR 2·64, 1·00 to 6·95; P = 0·049). CONCLUSION: Despite a higher rate of axillary recurrence with ANS combined with radiotherapy to the axilla, ANC did not improve overall, breast cancer-specific or metastasis-free survival. Axillary recurrence is thus not a satisfactory endpoint when comparing axillary treatments.

Time dependence of biomarkers: non-proportional effects of immunohistochemical panels predicting relapse risk in early breast cancer.

BACKGROUND: We investigated the impact of follow-up duration to determine whether two immunohistochemical prognostic panels, IHC4 and Mammostrat, provide information on the risk of early or late distant recurrence using the Edinburgh Breast Conservation Series and the Tamoxifen vs Exemestane Adjuvant Multinational (TEAM) trial. METHODS: The multivariable fractional polynomial time (MFPT) algorithm was used to determine which variables had possible non-proportional effects. The performance of the scores was assessed at various lengths of follow-up and Cox regression modelling was performed over the intervals of 0-5 years and >5 years. RESULTS: We observed a strong time dependence of both the IHC4 and Mammostrat scores, with their effects decreasing over time. In the first 5 years of follow-up only, the addition of both scores to clinical factors provided statistically significant information (P<0.05), with increases in R(2) between 5 and 6% and increases in D-statistic between 0.16 and 0.21. CONCLUSIONS: Our analyses confirm that the IHC4 and Mammostrat scores are strong prognostic factors for time to distant recurrence but this is restricted to the first 5 years after diagnosis. This provides evidence for their combined use to predict early recurrence events in order to select those patients who may/will benefit from adjuvant chemotherapy.

The Texas Children's Hospital immunization forecaster: conceptualization to implementation.

OBJECTIVES: Immunization forecasting systems evaluate patient vaccination histories and recommend the dates and vaccines that should be administered. We described the conceptualization, development, implementation, and distribution of a novel immunization forecaster, the Texas Children's Hospital (TCH) Forecaster. METHODS: In 2007, TCH convened an internal expert team that included a pediatrician, immunization nurse, software engineer, and immunization subject matter experts to develop the TCH Forecaster. Our team developed the design of the model, wrote the software, populated the Excel tables, integrated the software, and tested the Forecaster. We created a table of rules that contained each vaccine's recommendations, minimum ages and intervals, and contraindications, which served as the basis for the TCH Forecaster. RESULTS: We created 15 vaccine tables that incorporated 79 unique dose states and 84 vaccine types to operationalize the entire United States recommended immunization schedule. The TCH Forecaster was implemented throughout the TCH system, the Indian Health Service, and the Virginia Department of Health. The TCH Forecast Tester is currently being used nationally. CONCLUSIONS: Immunization forecasting systems might positively affect adherence to vaccine recommendations. Efforts to support health care provider utilization of immunization forecasting systems and to evaluate their impact on patient care are needed.

Folic acid pathway single nucleotide polymorphisms associated with methotrexate significant adverse events in United States veterans with rheumatoid arthritis.

OBJECTIVES: Methotrexate (MTX) is the cornerstone medication in the treatment of rheumatoid arthritis (RA). We examined whether single nucleotide polymorphisms (SNPs) in enzymes of the folic acid pathway (folylpoly-gamma-glutamate synthetase [FPGS], gamma-glutamyl hydrolase [GGH], and methylenetetrahydrofolate reductase [MTHFR]) associate with significant adverse events (SigAE). METHODS: Patients (n=319) enrolled in the Veterans Affairs RA (VARA) registry taking MTX were genotyped for HLA-DRB1-SE and the following SNPs: FPGS (rs7033913, rs10760503, rs10106), GGH (12548933, rs7010484, rs4617146, rs719235, rs11988534), MTHFR (rs1801131, rs1801133). AE were abstracted from the medical record using a structured instrument. SigAE were defined as an AE leading to MTX discontinuation. Covariates included: age, gender, race, RA antibody status, tobacco, RA disease duration between diagnosis and MTX course, Charlson-Deyo comorbidity index, glucocorticoids, use of prior RA medications, and mean 4-variable disease activity score. Cox regression was performed to determine factors associated with time-to-SigAE. A p-value ≤ 0.005 established significance in the final model. RESULTS: The presence of ≥ 1 copy of the minor allele in MTHFR rs1801131 was associated with an increased hazard ratio (HR) of SigAE (HR 3.05, 95% CI 1.48-6.29, p-value 0.003 and HR 3.88, 95% CI 1.62-9.28, p-value 0.002 for heterozygotes and homozygotes for the minor allele, respectively). An interaction term, between FPGS rs7033913 heterozygotes and GGH rs11988534 homozygotes for the minor allele, had a p-value <0.0001. CONCLUSIONS: RA subjects taking MTX may have decreased time-to-SigAE with ≥ 1 copy of the minor allele in MTHFR rs1801131. Further investigation is warranted, as these SNPs may indicate susceptibility to MTX toxicity.

The perspectives of adults with venous leg ulcers on exercise: an exploratory study.

OBJECTIVE: Exercise has the potential to offer a range of health benefits in addition to improving healing outcomes for people with venous leg ulcers (VLUs). However, despite evidence-based recommendations, most of these individuals do not engage in regular exercise. The aim of this study was to gain an understanding of the perspectives of adults with VLUs, in relation to exercise. METHOD: This was a qualitative design using semi-structured interviews and discussions. Ten participants with venous leg ulceration volunteered to participate. Recruitment was through a specialist wound clinic. Verbatim data were collected by an experienced moderator using a semi-structured guide. Data saturation was reached after three group discussions and two interviews. A random selection of transcripts was sent back to the participants for verification. Thematic content analysis was used to determine major themes and categories. Two transcripts were independently analysed, categories and themes independently developed, cross checked and found comparable. Remaining transcripts were analysed using the developed categories and codes. RESULTS: Regardless of their current exercise routine, participants reported exercising before venous leg ulceration and expressed an interest in either becoming active or maintaining an active lifestyle. Overall, four themes emerged from the findings: i) participant understanding of the relationship between chronic venous insufficiency and exercise patterns; ii) fear of harm impacts upon positive beliefs and attitudes to exercise; iii) perceived factors limit exercise; and iv) structured management facilitates exercise. CONCLUSION: The value of exercise in improving outcomes in VLUs lies in its capacity to promote venous return and reduce the risk of secondary conditions in this population. Despite motivation and interest in being exercise active, people with VLUs report many obstacles. Further exploration of mechanisms that assist this patient population and promote understanding about management of barriers, coupled with promotion of enabling factors, is vital for improving their exercise participation.

Predicting the bodily self in space and time.

To understand how the human brain distinguishes itself from external stimulation, it was examined if motor predictions enable healthy adult volunteers to infer self-location and to distinguish their body from the environment (and other agents). By uniquely combining a VR-setup with full-body motion capture, a full-body illusion paradigm (FBI) was developed with different levels of motion control: (A) a standard, passive FBI in which they had no motion control; (B) an active FBI in which they made simple, voluntary movements; and (C) an immersive game in which they real-time controlled a human-sized avatar in third person. Systematic comparisons between measures revealed a causal relationship between (i) motion control (prospective agency), (ii) self-other identification, and (iii) the ability to locate oneself. Healthy adults could recognise their movements in a third-person avatar and psychologically align with it (action observation); but did not lose a sense of place (self-location), time (temporal binding), nor who they are (self/other). Instead, motor predictions enabled them to localise their body and to distinguish self from other. In the future, embodied games could target and strengthen the brain's control networks in psychosis and neurodegeneration; real-time motion simulations could help advance neurorehabilitation techniques by fine-tuning and personalising therapeutic settings.

Orchidectomy after primary chemotherapy for metastatic testicular cancer.

OBJECTIVE: To examine the outcome of orchidectomy following primary chemotherapy in patients with metastatic testicular cancer. PATIENTS AND METHODS: This was a retrospective analysis of patients who underwent primary chemotherapy without initial orchidectomy for testicular cancer between 1982 and 2006. The patients were identified from the regional oncology cancer database in our tertiary referral hospital. Their case notes were reviewed regarding initial presentation, chemotherapy, clinical progress and pathological outcomes following surgery. RESULTS: 21 evaluable patients were identified (14 non-seminomatous germ cell tumours, 7 seminomas). 16 patients underwent standard orchidectomy within 12 months of commencing chemotherapy and 5 patients underwent significantly delayed orchidectomy (19-68 months, mean 45.1 months). Orchidectomy in the standard group showed tumour necrosis or a scar in 13 patients (81%) and differentiated or mature teratoma in 3 patients associated with bulky poorly responsive retroperitoneal disease (19%). In the delayed orchidectomy group 3 out of 5 patients had viable seminoma, of which two were associated with carcinoma in situ. CONCLUSION: Our study raises concerns as regards a potentially high risk of late tumour development in testes which are preserved following apparent tumour resolution after chemotherapy.

The effect of standing posture on amplitude and variability of postural tremor in Parkinson's disease.

INTRODUCTION: This study examined whether altering body position (i.e., sitting or standing) affected the dynamics of physiological tremor for healthy older adults and persons with Parkinson's disease (PD). It was also of interest to determine how consistent the tremor was for both groups as determined by examining changes in within-subject variability of tremor amplitude, regularity and frequency. METHODS: Ten Parkinsonian participants (65.1 ± 3.2 yrs.) and twelve elderly persons (71.2 ± 2.6 yrs.) participated in this study. Tremor was collected from the index finger and hand segments using lightweight accelerometers during the performance of a bilateral pointing task. Persons performed the pointing task in a standing or sitting position. RESULTS: As expected, the tremor for the PD persons was greater in magnitude (mean RMS, peak power), more regular (lower SampEn), and more inconsistent from trial-to-trial (increased intra-individual variability, IIV) than the tremor recorded for the elderly. Further, when assessed during standing, the magnitude of the tremor for all individuals (elderly and PD) was greater, more variable, and less complex compared to the tremor when assessed during the sitting posture. The only measure which did not change within each group was the frequency of the major tremor peak which remained consistent, showing no significant change between limbs or as a function of the posture adopted. CONCLUSION: The findings revealed that tremor increased in amplitude and decreased in regularity for all individuals was assessed when standing compared to sitting. It is likely that these increases were task-related, reflecting the increased physical demands of performing the task when standing rather than being driven by specific age- or disease-related changes in the mechanisms underlying tremorgenesis. Further, the tremor for the PD individuals tended to be more variable from trial-by-trial in terms of both amplitude and regularity as compared to the elderly persons. Interestingly, the only tremor metric which showed no change within each group was the frequency of the major tremor peak which was consistent within both groups irrespective of the posture adopted.

NOD1 mediates interleukin-18 processing in epithelial cells responding to Helicobacter pylori infection in mice.

The interleukin-1 family members, IL-1ß and IL-18, are processed into their biologically active forms by multi-protein complexes, known as inflammasomes. Although the inflammasome pathways that mediate IL-1ß processing in myeloid cells have been defined, those involved in IL-18 processing, particularly in non-myeloid cells, are still not well understood. Here we report that the host defence molecule NOD1 regulates IL-18 processing in mouse epithelial cells in response to the mucosal pathogen, Helicobacter pylori. Specifically, NOD1 in epithelial cells mediates IL-18 processing and maturation via interactions with caspase-1, instead of the canonical inflammasome pathway involving RIPK2, NF-κB, NLRP3 and ASC. NOD1 activation and IL-18 then help maintain epithelial homoeostasis to mediate protection against pre-neoplastic changes induced by gastric H. pylori infection in vivo. Our findings thus demonstrate a function for NOD1 in epithelial cell production of bioactive IL-18 and protection against H. pylori-induced pathology.

Benefit of chemotherapy as part of treatment for HPV DNA-positive but p16-negative squamous cell carcinoma of the oropharynx.

BACKGROUND: To determine (a) the cause of an improvement in survival from oropharyngeal squamous cell carcinoma (OSCC) in South East Scotland and (b) whether this improvement was human papillomavirus (HPV) and p16 subtype-dependent. METHODS: Clinicopathological characteristics and outcome data for patients referred with OSCC from 1999 to 2001 (Cohort-1) and 2003 to 2005 (Cohort-2) were obtained. Molecular HPV detection and immunohistochemistry for p16 were performed from paraffin blocks. RESULTS: Cohort-1 and Cohort-2 contained 118 and 136 patients, respectively. Kaplan-Meier analysis revealed significantly improved survival in Cohort-2 (P<0.0001). Sub-classification according to HPV and p16 status revealed no improvement in survival in Class-I (HPV-ve/p16-ve; 47 patients) or Class-III (HPV+ve/p16+ve; 77 patients). However in Class-II (HPV+ve/p16-ve; 56 patients) an increase in 5-year cause-specific survival from 36% in Cohort-1 to 73% in Cohort-2 was detected (P=0.0001).Proportional hazards analysis of 217 patients treated radically demonstrated that significant variables were p16 (P<0.0001), N stage (P=0.0006) and cohort (P=0.0024). Removing cohort from the variables offered to the model showed that, whereas p16 (P<0.0001) and N stage (P=0.0016) remain significant, chemotherapy (P=0.0163) and T stage (P=0.0139) are now significant. This suggests that much of the cohort effect is due to the higher use of chemotherapy in the second cohort. CONCLUSION: These data suggest that HPV+ve/p16-ve patients constitute a separate subclass of OSCC who may particularly benefit from chemotherapy. They imply that p16 status cannot be considered a surrogate for HPV status, and those trials to de-escalate treatment in HPV+ve OSCC should take p16 status into account.

Irish Defence Forces combat medical technician training: experience of a novel university medical school-based programme.

AIMS: This study explores the opinions and experiences of Irish Defences Forces' (IDF) graduates from University College Dublin's Diploma in Military Medicine Care (DMMC). It aims to identify which aspects of medical education are relevant for the development of military graduates in the role of Combat Medical Technician (CMT) in future. METHODS: A validated Clinical Learning Environment Score tool was adapted and incorporated into an online survey. This was sent electronically to 71 graduates. Responses were anonymous. RESULTS: 38 (54%) graduates responded. Student feedback was positive regarding teaching and clinical placements in the DMMC. In total 16 (42%) students reported use of their new skills in their daily work. Of the 9 (24%) deployed overseas, all used their new skills. Emergency and occupational health skills were used more frequently, while advanced skills were used rarely. CONCLUSION: An increased emphasis on frequently used skills should be considered. Links to healthcare services would be of benefit to graduates in skills maintenance. Key advanced skills, such as intravenous cannulation and advanced airway management are rarely used but mechanisms to maintain them will improve the relevance of the programme to the CMT role. A change in how the IDF acknowledges qualifications may support more graduates in advancing and maintaining their career in the military medical workforce.

Trends in classification, referral and treatment and the effect on outcome of patients with glioma: a 20 year cohort.

This retrospective audit was conducted to examine the changes in patient characteristics, referral, treatment and outcome over a 20-year period in a large regional neuro-oncology centre, focusing on the impact of the changes in pathological classification of gliomas. Using the Edinburgh Cancer Centre (ECC) database all cases of glioma were identified and patient, tumour and treatment characteristics noted. Survival was calculated from date of surgery or, if no operation was performed, the date of referral. Comparison was made between four periods 1988-1992 (c1), 1993-1997(c2), 1998-2002(c3) and 2003-2007 (c4). During the 20 years, 1175 patients with a glioma were referred to ECC. The median age increased from 53 years to 57 years (p < 0.001) but the proportion without pathology remained unchanged (10%). The distribution of pathological grades changed over time Grade I-II: 24, 6, 6, and 6%, Grade III: 42, 27, 17, and 13% and Grade IV: 24, 61, 68, and 68% in c1, c2, c3 and c4, respectively (p < 0.001). Immediate RT was given to 68% (c1), 70% (c2), 78% (c3) and 79% (c4). Median interval from resection to RT reduced from 43 days (c1) to 36 days (c4) (p < 0.001). 5-year overall survival for patients with Grade III lesions increased: 21% (c1), 35% (c2), 37% (c3), 33% (c4) as did 1-year overall survival for Grade IV lesions: 18% (c1), 26% (c2), 29% (c3), 27% (c4)). This improvement probably reflects the change in pathological classification rather than a change in management. Proportional hazards analysis of grade IV 1993-2007 only (to reduce pathological variation) showed that younger age, frontal lesions, excision, higher RT dose had reduced hazard of death. Interval from surgery to RT had no impact on survival in this series.

Electromyographic activity in lower limb muscles is temporally associated with the slow phase of oxygen uptake during cycling.

Although the "slow" phase of pulmonary oxygen uptake (VO2) appears to represent energetic processes in contracting muscle, electromyographic evidence tends not to support this. The present study assessed normalized integrated electromyographic (NIEMG) activity in eight muscles that act about the hip, knee and ankle during 8 min of moderate (ventilatory threshold) cycling in six male cyclists. VO2 was measured breath by breath during four repeated trials at each of the two intensities. Moderate and very heavy exercise followed a 4-min period of light exercise (50 W). During moderate exercise the slow VO2 phase was absent and NIEMG in all muscles did not increase after the first minute of exercise. During very heavy exercise, the slow VO2 phase emerged (time delay=58 +/- 16 s) and increased progressively (time constant=120 +/- 35 s) to an amplitude (0.83 +/- 0.16 L/min) that was approximately 21% of the total response. This slow VO2 phase coincided with a significant increase in NIEMG in most muscles, and differences in NIEMG activities between the two intensities revealed "slow" muscle activation profiles that differed between muscles in terms of the onset, amplitude and shape of these profiles. This supports the hypothesis that the slow phase VO2 is a function of these different slow muscle activation profiles.

Comparison of microarray preprocessing methods.

Data preprocessing in microarray technology is a crucial initial step before data analysis is performed. Many preprocessing methods have been proposed but none has proved to be ideal to date. Frequently, datasets are limited by laboratory constraints so that the need is for guidelines on quality and robustness, to inform further experimentation while data are yet restricted. In this paper, we compared the performance of four popular methods, namely MAS5, Li & Wong pmonly (LWPM), Li & Wong subtractMM (LWMM), and Robust Multichip Average (RMA). The comparison is based on the analysis carried out on sets of laboratory-generated data from the Bioinformatics Lab, National Institute of Cellular Biotechnology (NICB), Dublin City University, Ireland. These experiments were designed to examine the effect of Bromodeoxyuridine (5-bromo-2-deoxyuridine, BrdU) treatment in deep lamellar keratoplasty (DLKP) cells. The methodology employed is to assess dispersion across the replicates and analyze the false discovery rate. From the dispersion analysis, we found that variability is reduced more effectively by LWPM and RMA methods. From the false positive analysis, and for both parametric and nonparametric approaches, LWMM is found to perform best. Based on a complementary q-value analysis, LWMM approach again is the strongest candidate. The indications are that, while LWMM is marginally less effective than LWPM and RMA in terms of variance reduction, it has considerably improved discrimination overall.

A causal role for the right angular gyrus in self-location mediated perspective taking.

Recent theories suggest that self-consciousness, in its most elementary form, is functionally disconnected from the phenomenal body. Patients with psychosis frequently misattribute their thoughts and actions to external sources; and in certain out-of-body experiences, lucid states, and dreams body-ownership is absent but self-identification is preserved. To explain these unusual experiences, we hypothesized that self-identification depends on inferring self-location at the right angular gyrus (i.e., perspective-taking). This process relates to the discrimination of self-produced signals (endogenous attention) from environmental stimulation (exogenous attention). Therefore, when this mechanism fails, this causes altered sensations and perceptions. We combined a Full-body Illusion paradigm with brain stimulation (HD-tDCS) and found a clear causal association between right angular gyrus activation and alterations in self-location (perspective-taking). Anodal versus sham HD-tDCS resulted in: a more profound out-of-body shift (with reduced sense of agency); and a weakened ability to discriminate self from other perspectives. We conclude that self-identification is mediated in the brain by inferring self-location (i.e., perspective-taking). Self-identification can be decoupled from the bodily self, explaining phenomena associated with disembodiment. These findings present novel insights into the relationship between mind and body, and may offer important future directions for treating psychosis symptoms and rehabilitation programs to aid in the recovery from a nervous system injury. The brain's ability to locate itself might be the key mechanism for self-identification and distinguishing self from other signals (i.e., perspective-taking).