Altered cell cycle regulation helps stem-like carcinoma cells resist apoptosis

Reemergence of carcinomas following chemotherapy and/or radiotherapy is not well understood, but a recent study in BMC Cancer suggests that resistance to apoptosis resulting from altered cell cycle regulation is crucial

Acquiring in situ training data for context-aware ubiquitous computing applications

Ubiquitous, context-aware computer systems may ultimately enable computer applications that naturally and usefully respond to a user's everyday activity. Although new algorithms that can automatically detect context from wearable and environmental sensor systems show promise, many of the most flexible and robust systems use probabilistic detection algorithms that require extensive libraries of training data with labeled examples. In this paper, we describe the need for such training data and some challenges we have identified when trying to collect it while testing three contextdetection systems for ubiquitous computing and mobile applications. Author Keywords Context-aware, ubiquitous, computing, supervised learning, experience sampling, user interface design ACM Classification Keywords H5.m Information interfaces and presentation (e.g. HCI): Miscellaneous

Watching individual molecules flex within lipid membranes using SERS.

Interrogating individual molecules within bio-membranes is key to deepening our understanding of biological processes essential for life. Using Raman spectroscopy to map molecular vibrations is ideal to non-destructively 'fingerprint' biomolecules for dynamic information on their molecular structure, composition and conformation. Such tag-free tracking of molecules within lipid bio-membranes can directly connect structure and function. In this paper, stable co-assembly with gold nano-components in a 'nanoparticle-on-mirror' geometry strongly enhances the local optical field and reduces the volume probed to a few nm(3), enabling repeated measurements for many tens of minutes on the same molecules. The intense gap plasmons are assembled around model bio-membranes providing molecular identification of the diffusing lipids. Our experiments clearly evidence measurement of individual lipids flexing through telltale rapid correlated vibrational shifts and intensity fluctuations in the Raman spectrum. These track molecules that undergo bending and conformational changes within the probe volume, through their interactions with the environment. This technique allows for in situ high-speed single-molecule investigations of the molecules embedded within lipid bio-membranes. It thus offers a new way to investigate the hidden dynamics of cell membranes important to a myriad of life processes.We acknowledge financial support from EPSRC grant EP/G060649/1, EP/I012060/1, ERC grant LINASS 320503. FB acknowledges support from the Winton Programme for the Physics of Sustainability.This is the final published version. It's also available from Nature Publishing at http://www.nature.com/srep/2014/140812/srep05940/full/srep05940.html

Lack of a functioning P2X7 receptor leads to increased susceptibility to toxoplasmic ileitis

Background: Oral infection of C57BL/6J mice with the protozoan parasite Toxoplasma gondii leads to a lethal inflammatory ileitis. Principal Findings: Mice lacking the purinergic receptor P2X7R are acutely susceptible to toxoplasmic ileitis, losing significantly more weight than C57BL/6J mice and exhibiting much greater intestinal inflammatory pathology in response to infection with only 10 cysts of T. gondii. This suscep-tibility is not dependent on the ability of P2X7R-deficient mice to control the parasite, which they accomplish just as efficiently as C57BL/6J mice. Rather, susceptibility is associated with elevated ileal concentrations of pro-inflammatory cytokines, reactive nitrogen interme-diates and altered regulation of elements of NFκB activation in P2X7R-deficient mice. Conclusions: Our data support the thesis that P2X7R, a well-documented activator of pro-inflammatory cytokine production, also plays an important role in the regulation of intestinal inflammation

Biomechanical risk factors for carpal tunnel syndrome: a pooled study of 2474 workers

BACKGROUND: Between 2001 and 2010, five research groups conducted coordinated prospective studies of carpal tunnel syndrome (CTS) incidence among US workers from various industries and collected detailed subject-level exposure information with follow-up of symptoms, electrophysiological measures and job changes. OBJECTIVE: This analysis examined the associations between workplace biomechanical factors and incidence of dominant-hand CTS, adjusting for personal risk factors. METHODS: 2474 participants, without CTS or possible polyneuropathy at enrolment, were followed up to 6.5 years (5102 person-years). Individual workplace exposure measures of the dominant hand were collected for each task and included force, repetition, duty cycle and posture. Task exposures were combined across the workweek using time-weighted averaging to estimate job-level exposures. CTS case-criteria were based on symptoms and results of electrophysiological testing. HRs were estimated using Cox proportional hazard models. RESULTS: After adjustment for covariates, analyst (HR=2.17; 95% CI 1.38 to 3.43) and worker (HR=2.08; 95% CI 1.31 to 3.39) estimated peak hand force, forceful repetition rate (HR=1.84; 95% CI 1.19 to 2.86) and per cent time spent (eg, duty cycle) in forceful hand exertions (HR=2.05; 95% CI 1.34 to 3.15) were associated with increased risk of incident CTS. Associations were not observed between total hand repetition rate, per cent duration of all hand exertions, or wrist posture and incident CTS. CONCLUSIONS: In this prospective multicentre study of production and service workers, measures of exposure to forceful hand exertion were associated with incident CTS after controlling for important covariates. These findings may influence the design of workplace safety programmes for preventing work-related CTS

General population job exposure matrix applied to a pooled study of prevalent carpal tunnel syndrome

A job exposure matrix may be useful for the study of biomechanical workplace risk factors when individual-level exposure data are unavailable. We used job title–based exposure data from a public data source to construct a job exposure matrix and test exposure-response relationships with prevalent carpal tunnel syndrome (CTS). Exposures of repetitive motion and force from the Occupational Information Network were assigned to 3,452 active workers from several industries, enrolled between 2001 and 2008 from 6 studies. Repetitive motion and force exposures were combined into high/high, high/low, and low/low exposure groupings in each of 4 multivariable logistic regression models, adjusted for personal factors. Although force measures alone were not independent predictors of CTS in these data, strong associations between combined physical exposures of force and repetition and CTS were observed in all models. Consistent with previous literature, this report shows that workers with high force/high repetition jobs had the highest prevalence of CTS (odds ratio = 2.14–2.95) followed by intermediate values (odds ratio = 1.09–2.27) in mixed exposed jobs relative to the lowest exposed workers. This study supports the use of a general population job exposure matrix to estimate workplace physical exposures in epidemiologic studies of musculoskeletal disorders when measures of individual exposures are unavailable

Exposure-response relationships for the ACGIH threshold limit value for hand-activity level: results from a pooled data study of carpal tunnel syndrome

OBJECTIVE: This paper aimed to quantify exposure–response relationships between the American Conference of Governmental Industrial Hygienists’ (ACGIH) threshold limit value (TLV) for hand-activity level (HAL) and incidence of carpal tunnel syndrome (CTS). METHODS: Manufacturing and service workers previously studied by six research institutions had their data combined and re-analyzed. CTS cases were defined by symptoms and abnormal nerve conduction. Hazard ratios (HR) were calculated using proportional hazards regression after adjusting for age, gender, body mass index, and CTS predisposing conditions. RESULTS: The longitudinal study comprised 2751 incident-eligible workers, followed prospectively for up to 6.4 years and contributing 6243 person-years of data. Associations were found between CTS and TLV for HAL both as a continuous variable [HR 1.32 per unit, 95% confidence interval (95% CI) 1.11–1.57] and when categorized using the ACGIH action limit (AL) and TLV. Those between the AL and TLV and above the TLV had HR of 1.7 (95% CI 1.2–2.5) and 1.5 (95% CI 1.0–2.1), respectively. As independent variables (in the same adjusted model) the HR for peak force (PF) and HAL were 1.14 per unit (95% CI 1.05–1.25), and 1.04 per unit (95% CI 0.93–1.15), respectively. CONCLUSION: Those with exposures above the AL were at increased risk of CTS, but there was no further increase in risk for workers above the TLV. This suggests that the current AL may not be sufficiently protective of workers. Combinations of PF and HAL are useful for predicting risk of CTS

Developing a pooled job physical exposure data set from multiple independent studies: An example of a consortium study of carpal tunnel syndrome

BackgroundSix research groups independently conducted prospective studies of carpal tunnel syndrome (CTS) incidence in 54 US workplaces in 10 US States. Physical exposure variables were collected by all research groups at the individual worker level. Data from these research groups were pooled to increase the exposure spectrum and statistical power.ObjectiveThis paper provides a detailed description of the characteristics of the pooled physical exposure variables and the source data information from the individual research studies.MethodsPhysical exposure data were inspected and prepared by each of the individual research studies according to detailed instructions provided by an exposure subcommittee of the research consortium. Descriptive analyses were performed on the pooled physical exposure data set. Correlation analyses were performed among exposure variables estimating similar exposure aspects.ResultsAt baseline, there were a total of 3010 participants in the pooled physical exposure data set. Overall, the pooled data meaningfully increased the spectra of most exposure variables. The increased spectra were due to the wider range in exposure data of different jobs provided by the research studies. The correlations between variables estimating similar exposure aspects showed different patterns among data provided by the research studies.ConclusionsThe increased spectra of the physical exposure variables among the data pooled likely improved the possibility of detecting potential associations between these physical exposure variables and CTS incidence. It is also recognised that methods need to be developed for general use by all researchers for standardisation of physical exposure variable definition, data collection, processing and reduction

Personal and workplace psychosocial risk factors for carpal tunnel syndrome: a pooled study cohort

BACKGROUND: Between 2001 and 2010, six research groups conducted coordinated multiyear, prospective studies of carpal tunnel syndrome (CTS) incidence in US workers from various industries and collected detailed subject-level exposure information with follow-up symptom, physical examination, electrophysiological measures and job changes. OBJECTIVE: This analysis of the pooled cohort examined the incidence of dominant-hand CTS in relation to demographic characteristics and estimated associations with occupational psychosocial factors and years worked, adjusting for confounding by personal risk factors. METHODS: 3515 participants, without baseline CTS, were followed-up to 7 years. Case criteria included symptoms and an electrodiagnostic study consistent with CTS. Adjusted HRs were estimated in Cox proportional hazard models. Workplace biomechanical factors were collected but not evaluated in this analysis. RESULTS: Women were at elevated risk for CTS (HR=1.30; 95% CI 0.98 to 1.72), and the incidence of CTS increased linearly with both age and body mass index (BMI) over most of the observed range. High job strain increased risk (HR=1.86; 95% CI 1.11 to 3.14), and social support was protective (HR=0.54; 95% CI 0.31 to 0.95). There was an inverse relationship with years worked among recent hires with the highest incidence in the first 3.5 years of work (HR=3.08; 95% CI 1.55 to 6.12). CONCLUSIONS: Personal factors associated with an increased risk of developing CTS were BMI, age and being a woman. Workplace risk factors were high job strain, while social support was protective. The inverse relationship between CTS incidence and years worked among recent hires suggests the presence of a healthy worker survivor effect in the cohort