LIGHTSITE III: 13-Month Efficacy and Safety Evaluation of Multiwavelength Photobiomodulation in Nonexudative (Dry) Age-Related Macular Degeneration Using the Lumithera Valeda Light Delivery System.

PURPOSE: The LIGHTSITE III study evaluated multiwavelength photobiomodulation (PBM) therapy in nonexudative (dry) age-related macular degeneration (AMD) using the LumiThera Valeda Light Delivery System. METHODS: LIGHTSITE III is a randomized, controlled trial to assess the safety and effectiveness of PBM in dry AMD. Subjects were given multiwavelength PBM (590, 660, and 850 nm) or Sham treatment delivered in a series of nine sessions over 3 to 5 weeks every four months over 24 months. Subjects were assessed for efficacy and safety outcomes. Data from the 13-month analysis are presented in this report. RESULTS: A total of 100 subjects (148 eyes) with dry AMD were randomized. LIGHTSITE III met the primary efficacy best-corrected visual acuity endpoint with a significant difference between PBM (n = 91 eyes) and Sham (n = 54 eyes) groups (Between group difference: 2.4 letters (SE 1.15), CI: -4.7 to -0.1, P = 0.02) (PBM alone: 5.4 letters (SE 0.96), CI: 3.5 to 7.3, P < 0.0001; Sham alone: 3.0 letters (SE 1.13), CI: 0.7-5.2, P < 0.0001). The PBM group showed a significant decrease in new onset geographic atrophy ( P = 0.024, Fisher exact test, odds ratio 9.4). A favorable safety profile was observed. CONCLUSION: LIGHTSITE III provides a prospective, randomized, controlled trial showing improved clinical and anatomical outcomes in intermediate dry AMD following PBM therapy.

Bioinformatic Analysis of Topoisomerase IIα Reveals Interdomain Interdependencies and Critical C-Terminal Domain Residues.

DNA Topoisomerase IIα (Top2A) is a nuclear enzyme that is a cancer drug target, and there is interest in identifying novel sites on the enzyme to inhibit cancer cells more selectively and to reduce off-target toxicity. The C-terminal domain (CTD) is one potential target, but it is an intrinsically disordered domain, which prevents structural analysis. Therefore, we set out to analyze the sequence of Top2A from 105 species using bioinformatic analysis, including the PSICalc algorithm, Shannon entropy analysis, and other approaches. Our results demonstrate that large (10th-order) interdependent clusters are found including non-proximal positions across the major domains of Top2A. Further, CTD-specific clusters of the third, fourth, and fifth order, including positions that had been previously analyzed via mutation and biochemical assays, were identified. Some of these clusters coincided with positions that, when mutated, either increased or decreased relaxation activity. Finally, sites of low Shannon entropy (i.e., low variation in amino acids at a given site) were identified and mapped as key positions in the CTD. Included in the low-entropy sites are phosphorylation sites and charged positions. Together, these results help to build a clearer picture of the critical positions in the CTD and provide potential sites/regions for further analysis.

Commercial weight management programmes for patients living with overweight or obesity prior to elective orthopaedic surgery: an evidence review.

BACKGROUND: Increased body mass index is associated with increased operative risk during elective joint replacement surgery. Commercial weight management programmes are designed to achieve weight loss. It is not known whether commercial weight management programmes are effective at achieving weight loss in patients awaiting planned hip or knee replacement surgery, or whether achieving significant planned weight loss prior to surgery is associated with changes in surgical outcome. METHODS: A systematic literature search of seven databases was conducted. Reference lists and grey literature were searched, including commercial weight management programme and medical association websites. Four relevant primary interventional studies were identified. RESULTS: There is weak, low-quality evidence from four small studies, of which three demonstrated that commercial weight management programmes initiated between 3 and 6 months prior to elective joint replacement surgery are associated with a statistically significant weight loss and body mass index reduction. There is a weak evidence from two studies that peri- and post-operative complications are similar between control and commercial weight management programme groups. CONCLUSION: There is a paucity of studies investigating commercial weight management programmes aiming to reduce weight in patients living with overweight or obesity awaiting total joint replacement. Further, high-quality research is urgently needed.

Correction to: Lean mass and lower limb muscle function in relation to hip strength, geometry and fracture risk indices in community-dwelling older women.

The original version of this article, published on 14 December 2018, unfortunately contained a mistake.

The importance of the laser pulse-ablator interaction dynamics prior to the ablation plasma phase in inertial confinement fusion studies.

This work presents studies which demonstrate the importance of the very early heating dynamics of the ablator long before the ablation plasma phase begins in laser driven inertial confinement fusion (ICF) studies. For the direct-drive fusion concept using lasers, the development of perturbations during the thermo-elasto-plastic (TEP) and melting phases of the interaction of the laser pulse with the ablator's surface may act as seeding to the subsequent growth of hydro-dynamic instabilities apparent during the acceleration phase of the interaction such as for instance the Rayleigh-Taylor and the Richtmyer-Meshkov, which strongly affect the implosion dynamics of the compression phase. The multiphysics-multiphase finite-element method (FEM) simulation results are experimentally validated by advanced three-dimensional whole-field dynamic imaging of the surface of the ablator allowing for a transverse to the surface spatial resolution of only approximately 1 nm. The study shows that the TEP and melting phases of the interaction are of crucial importance since transverse perturbations of the ablator's surface can reach tens of nanometres in amplitude within the TEP and melting phases. Such perturbations are of Rayleigh type and are transferred from the ablator to the substrate from the very first moments of the interaction. This article is part of a discussion meeting issue 'Prospects for high gain inertial fusion energy (part 1)'.

A DOUBLE-MASKED, RANDOMIZED, SHAM-CONTROLLED, SINGLE-CENTER STUDY WITH PHOTOBIOMODULATION FOR THE TREATMENT OF DRY AGE-RELATED MACULAR DEGENERATION.

PURPOSE: The LIGHTSITE I study investigated the efficacy and safety of photobiomodulation (PBM) treatment in subjects with dry age-related macular degeneration. METHODS: Thirty subjects (46 eyes) were treated with the Valeda Light Delivery System, wherein subjects underwent two series of treatments (3× per week for 3-4 weeks) over 1 year. Outcome measures included best-corrected visual acuity, contrast sensitivity, microperimetry, central drusen volume and drusen thickness, and quality of life assessments. RESULTS: Photobiomodulation-treated subjects showed a best-corrected visual acuity mean letter score gain of 4 letters immediately after each treatment series at Month 1 (M1) and Month 7 (M7). Approximately 50% of PBM-treated subjects showed improvement of ≥5 letters versus 13.6% in sham-treated subjects at M1. High responding subjects (≥5-letter improvement) in the PBM-treated group showed a gain of 8 letters after initial treatment (P < 0.01) and exhibited earlier stages of age-related macular degeneration disease. Statistically significant improvements in contrast sensitivity, central drusen volume, central drusen thickness, and quality of life were observed (P < 0.05). No device-related adverse events were reported. CONCLUSION: Photobiomodulation treatment statistically improved clinical and anatomical outcomes with more robust benefits observed in subjects with earlier stages of dry age-related macular degeneration. Repeated PBM treatments are necessary to maintain benefits. These pilot findings support previous reports and suggest the utility of PBM as a safe and effective therapy in subjects with dry age-related macular degeneration.

Dissemination of multiple carbapenem resistance genes in an in vitro gut model simulating the human colon.

BACKGROUND: Carbapenemase-producing Enterobacteriaceae (CPE) pose a major global health risk. Mobile genetic elements account for much of the increasing CPE burden. OBJECTIVES: To investigate CPE colonization and the impact of antibiotic exposure on subsequent resistance gene dissemination within the gut microbiota using a model to simulate the human colon. METHODS: Gut models seeded with CPE-negative human faeces [screened with BioMérieux chromID® CARBA-SMART (Carba-Smart), Cepheid Xpert® Carba-R assay (XCR)] were inoculated with distinct carbapenemase-producing Klebsiella pneumoniae strains (KPC, NDM) and challenged with imipenem or piperacillin/tazobactam then meropenem. Resistant populations were enumerated daily on selective agars (Carba-Smart); CPE genes were confirmed by PCR (XCR, Check-Direct CPE Screen for BD MAX™). CPE gene dissemination was tracked using PacBio long-read sequencing. RESULTS: CPE populations increased during inoculation, plateauing at ∼105 log10 cfu/mL in both models and persisting throughout the experiments (>65 days), with no evidence of CPE 'washout'. After antibiotic administration, there was evidence of interspecies plasmid transfer of blaKPC-2 (111742 bp IncFII/IncR plasmid, 99% identity to pKpQIL-D2) and blaNDM-1 (∼170 kb IncFIB/IncFII plasmid), and CPE populations rose from <0.01% to >45% of the total lactose-fermenting populations in the KPC model. Isolation of a blaNDM-1K. pneumoniae with one chromosomal single-nucleotide variant compared with the inoculated strain indicated clonal expansion within the model. Antibiotic administration exposed a previously undetected K. pneumoniae encoding blaOXA-232 (KPC model). CONCLUSIONS: CPE exposure can lead to colonization, clonal expansion and resistance gene transfer within intact human colonic microbiota. Furthermore, under antibiotic selective pressure, new resistant populations emerge, emphasizing the need to control exposure to antimicrobials.

Impact of mild and moderate/severe vertebral fractures on physical activity: a prospective study of older women in the UK.

Little is known about the long-term impact of vertebral fractures on physical activity. There is also uncertainty over the clinical significance of mild vertebral fracture. We showed that women with moderate/severe but not mild vertebral fracture do less walking duration and housework than those without fracture after 5.4 years of follow-up. INTRODUCTION: Little is known about the long-term impact of vertebral fractures on physical activities. There is also uncertainty over the clinical significance of mild fracture. Therefore, the aim of this study was to evaluate the prospective association between vertebral fracture and future physical activity. METHODS: This is a 5-year prospective study of a mixed community and secondary care cohort of women aged > 50 from the UK. Vertebral fractures were identified at baseline on radiographs or DXA-based Vertebral Fracture Assessment by a Quantitative Morphometric approach and defined as moderate/severe (≥ 25% height decrease) or mild (20-24.9% height decrease). Physical activity data were collected 5.4 years later by self-completion questionnaires. Multivariable logistic regression was used to determine the association between presence of fracture and various physical activities while adjusting for potential confounders. RESULTS: Two hundred eighty-six women without, 58 with mild, and 69 with moderate/severe fracture were recruited. Those with mild and moderate/severe fracture were older than women without fracture and had more concomitant diseases at baseline. At 5.4 years follow-up, women with moderate/severe fracture self-reported shorter walking duration compared to those without fracture, even after adjusting for potential confounders (OR 2.96, 95%CI 1.11-7.88, P = 0.030). No independent association was seen between the presence of mild fractures and reduced physical activity at follow-up. CONCLUSION: This is the first study of older women from the UK that explored the prospective association between vertebral fracture and physical activity duration. Moderate/severe fractures were associated with reduced walking duration. Mild fractures had no impact on future physical ability.

Lean mass and lower limb muscle function in relation to hip strength, geometry and fracture risk indices in community-dwelling older women.

In a population-based sample of British women aged over 70 years old, lean mass and peak lower limb muscle force were both independently associated with hip strength and fracture risk indices, thereby suggesting a potential benefit of promoting leg muscle strengthening exercise for the prevention of hip fractures in postmenopausal women. INTRODUCTION: To investigate cross-sectional associations of lean mass and physical performance, including lower limb muscle function, with hip strength, geometry and fracture risk indices (FRIs) in postmenopausal women. METHODS: Data were from the Cohort of Skeletal Health in Bristol and Avon. Total hip (TH) and femoral neck (FN) bone mineral density (BMD), hip geometry and total body lean mass (TBLM) were assessed by dual x-ray absorptiometry (DXA). Finite element analysis of hip DXA was used to derive FN, intertrochanteric and subtrochanteric FRIs. Grip strength, gait speed and chair rise time were measured objectively. Lower limb peak muscle force and muscle power were assessed by jumping mechanography. RESULTS: In total, 241 women were included (age = 76.4; SD = 2.6 years). After adjustment for age, height, weight/fat mass and comorbidities, TBLM was positively associated with hip BMD (ßTH BMD = 0.36, P ≤ 0.001; ßFN BMD = 0.26, P = 0.01) and cross-section moment of inertia (0.24, P ≤ 0.001) and inversely associated with FN FRI (- 0.21, P = 0.03) and intertrochanteric FRI (- 0.11, P = 0.05) (estimates represent SD difference in bone measures per SD difference in TBLM). Lower limb peak muscle force was positively associated with hip BMD (ßTH BMD = 0.28, P ≤ 0.001; ßFN BMD = 0.23, P = 0.008) and inversely associated with FN FRI (- 0.17, P = 0.04) and subtrochanteric FRI (- 0.18, P = 0.04). Associations of grip strength, gait speed, chair rise time and peak muscle power with hip parameters were close to the null. CONCLUSIONS: Lean mass and lower limb peak muscle force were associated with hip BMD and geometrical FRIs in postmenopausal women. Leg muscle strengthening exercises may therefore help prevent hip fractures in older women.

A Structured Approach to Detecting and Treating Depression in Primary Care: VitalSign6 Project.

PURPOSE: This report describes outcomes of an ongoing quality-improvement project (VitalSign6) in a large US metropolitan area to improve recognition, treatment, and outcomes of depressed patients in 16 primary care clinics (6 charity clinics, 6 federally qualified health care centers, 2 private clinics serving low-income populations, and 2 private clinics serving patients with either Medicare or private insurance). METHODS: Inclusion in this retrospective analysis was restricted to the first 25,000 patients (aged ≥12 years) screened with the 2-item Patient Health Questionnaire (PHQ-2) in the aforementioned quality-improvement project. Further evaluations with self-reports and clinician assessments were recorded for those with positive screen (PHQ-2 >2). Data collected from August 2014 though November 2016 were available at 3 levels: (1) initial PHQ-2 (n = 25,000), (2) positive screen (n = 4,325), and (3) clinician-diagnosed depressive disorder with 18 or more weeks of enrollment (n = 2,160). RESULTS: Overall, 17.3% (4,325/25,000) of patients screened positive for depression. Of positive screens, 56.1% (2,426/4,325) had clinician-diagnosed depressive disorder. Of those enrolled for 18 or more weeks, 64.8% were started on measurement-based pharmacotherapy and 8.9% referred externally. Of the 1,400 patients started on pharmacotherapy, 45.5%, 30.2%, 12.6%, and 11.6% had 0, 1, 2, and 3 or more follow-up visits, respectively. Remission rates were 20.3% (86/423), 31.6% (56/177), and 41.7% (68/163) for those with 1, 2, and 3 or more follow-up visits, respectively. Baseline characteristics associated with higher attrition were: non-white, positive drug-abuse screen, lower depression/anxiety symptom severity, and younger age. CONCLUSION: Although remission rates are high in those with 3 or more follow-up visits after routine screening and treatment of depression, attrition from care is a significant issue adversely affecting outcomes.

Improving the identification and treatment of depression in low-income primary care clinics: a qualitative study of providers in the VitalSign6 program.

QUALITY PROBLEM: Despite its global burden and prevalence, Major Depressive Disorder often goes undetected and untreated, and is particularly pervasive in the primary care setting. INITIAL ASSESSMENT: One in four Texans lack health insurance, and people with behavioral health disorders are disproportionately affected. It is possible to provide high-quality depression treatment in primary care settings with outcomes equal to those provided by specialty care. The Center for Depression Research and Clinical Care offered an opportunity to transform service delivery practices in underserved primary care practices to improve quality, health status, patient experience and coordination. CHOICE OF SOLUTION: A point-of-care, web-based, self-report based software program, VitalSign6, was developed to provide universal depression screening in primary care practices and assist providers in monitoring and treating patients' symptoms using principles of Measurement-Based Care. IMPLEMENTATION: Implementation included a multi-faceted training program designed to build confidence and competence in participating clinics' medical providers and staff as well as ongoing performance improvement delivered by the VitalSign6 team. EVALUATION: Primary care providers (N = 11) were interviewed, using a semi-structured interview guide, with a focus on barriers and challenges to full integration, perceptions of the most/least valuable aspects of the program, and the program's impact on knowledge, attitudes and behaviors about depression screening and treatment. LESSONS LEARNED: More efficient technology is needed to reduce time wasted, as is training to reduce stigma and correct misconceptions about antidepressant medications. Provider buy-in is essential. CONCLUSIONS: Despite barriers, VitalSign6 increased knowledge, changed attitudes and enhanced providers' depression screening and treatment skills over time.

Caries-preventive efficacy of a supervised school toothbrushing programme in Northland, New Zealand.

BACKGROUND: Toothbrushing with fluoride toothpaste reduces the incidence of dental caries. OBJECTIVE: To evaluate a supervised school toothbrushing programme to reduce dental caries experience in children. BASIC RESEARCH DESIGN: Quasi-experimental study. All children had routine dental examinations at baseline using the ICDAS to record dental caries, along with bitewing radiographs. Half of the children were involved in a supervised toothbrushing programme. Examinations were repeated at the end of the school year. CLINICAL SETTING: Northland, New Zealand. PARTICIPANTS: 335 10-13-year-old New Zealand children with high caries experience. INTERVENTIONS: Half of the children participated in the supervised toothbrushing session each school day; the other half had no intervention. MAIN OUTCOME MEASURES: Caries increment, determined by comparing the baseline and follow-up status of each tooth surface. RESULTS: At baseline, there were 335 children, of whom 240 (71.6%) were followed up. The ICDAS net caries increment for those in the toothbrushing group was a mean of 11.7 surfaces improved; the control group had a mean of 8.6 surfaces which had deteriorated. Caries incidence for those in the toothbrushing group was 7.3%; that for the control group was 71.5%. Multivariate analysis showed that membership of the brushing group was the only statistically significant predictor of a lower net caries increment. CONCLUSION: A supervised school toothbrushing programme can reduce caries increment in a population experiencing high levels of dental disease.

Self-reported everyday physical activities in older people with osteoporotic vertebral fractures: a systematic review and meta-analysis.

Previous work has shown that patients with vertebral fractures do less physical activity. However, the association between vertebral fracture and different components of physical activity is unclear. Our results suggest that vertebral fracture (VF) is associated with a reduction in activities involving bending, ambulation, and daily living, regardless of age. INTRODUCTION: The aim of this study was to determine whether osteoporotic VF is associated with reduced self-reported everyday routine physical activity and/or ability (PAA). METHODS: A comprehensive search was undertaken using the databases of PubMed, Embase, Medline, Web of Science, and the "grey" literature from 1950 to the end of July 2016. Standardised search terms for VF and PAAs were used. Four categories of PAA were included: (1) bending ability, (2) ambulatory activities, (3) reaching arms above shoulder level, and (4) activities of daily living (ADLs). Strict inclusion and exclusion criteria were used, and only studies that adjusted for age were included. For the meta-analysis, pooled OR and 95% confidence interval (CI) were calculated using a random-effects model. RESULTS: Eleven studies in total were identified which had investigated the associations between the prevalent VF and the selected PAAs and expressed these as ORs or RR. Women (six studies) with VF had a 64% increase in difficulty forward bending compared to those without VF. Women (nine studies) with VF had a 27% increase in difficulty doing ambulatory activities, while no association was observed for men (four studies). Women also have 73% (five studies), 127% (three studies), and 100% (four studies) increase in difficulty reaching arms above shoulder, shopping, and preparing meals, respectively. CONCLUSION: Studies consistently show women with VF have reduced everyday activities, while much less research has been carried out in men. This information may be useful when designing interventions to improve physical function in people with osteoporotic VFs.

Correction to: Using self-reports of pain and other variables to distinguish between older women with back pain due to vertebral fractures and those with back pain due to degenerative changes.

This article was originally published under a CC BY-NC-ND 4.0 license, but has now been made available under a CC BY 4.0 license. The PDF and HTML versions of the paper have been modified accordingly.

The genomic architecture of mastitis resistance in dairy sheep.

BACKGROUND: Mastitis is the most prevalent disease in dairy sheep with major economic, hygienic and welfare implications. The disease persists in all dairy sheep production systems despite the implementation of improved management practises. Selective breeding for enhanced mastitis resistance may provide the means to further control the disease. In the present study, we investigated the genetic architecture of four mastitis traits in dairy sheep. Individual animal records for clinical mastitis occurrence and three mastitis indicator traits (milk somatic cell count, total viable bacterial count in milk and the California mastitis test) were collected monthly throughout lactation for 609 ewes of the Greek Chios breed. All animals were genotyped with a custom-made 960-single nucleotide polymorphism (SNP) DNA array based on markers located in quantitative trait loci (QTL) regions for mastitis resistance previously detected in three other distinct dairy sheep populations. RESULTS: Heritable variation and strong positive genetic correlations were estimated for clinical mastitis occurrence and the three mastitis indicator traits. SNP markers significantly associated with these mastitis traits were confirmed on chromosomes 2, 3, 5, 16 and 19. We identified pathways, molecular interaction networks and functional gene clusters for mastitis resistance. Candidate genes within the detected regions were identified based upon analysis of an ovine transcriptional atlas and transcriptome data derived from milk somatic cells. Relevant candidate genes implicated in innate immunity included SOCS2, CTLA4, C6, C7, C9, PTGER4, DAB2, CARD6, OSMR, PLXNC1, IDH1, ICOS, FYB, and LYFR. CONCLUSIONS: The results confirmed the presence of animal genetic variability in mastitis resistance and identified genomic regions associated with specific mastitis traits in the Chios sheep. The conserved genetic architecture of mastitis resistance between distinct dairy sheep breeds suggests that across-breed selection programmes would be feasible.

Spinal radiographs in those with back pain-when are they appropriate to diagnose vertebral fractures?

The presence of an osteoporotic vertebral fracture improves fracture risk assessment and may change management, so it is vital for healthcare professionals to assess patients for the presence or absence of these fractures. This may be particularly important in the presence of back pain. However, the correlation between low back symptoms and spinal imaging results is poor and the pathophysiology of most low back pain is not known, leading to a common conclusion that spinal radiographs are not appropriate for the assessment of back pain. For individual patients with back pain, spinal radiographs should be considered if they have certain features in the history and examination. As well as the traditional risk factors for osteoporosis, self-reported descriptives of back pain and novel physical examination findings have been shown to make the presence of vertebral fractures more likely. Systematic approaches have the potential to improve bone health across the population but need to be targeted to be cost-effective. Spinal radiographs should be considered for individual older patients with back pain if they have certain additional features in the history and examination.

Habitual levels of higher, but not medium or low, impact physical activity are positively related to lower limb bone strength in older women: findings from a population-based study using accelerometers to classify impact magnitude.

This study assessed the effect of accelerometry-measured higher impacts resulting from habitual weight-bearing activity on lower limb bone strength in older women. Despite higher impacts being experienced rarely in this population-based cohort, positive associations were observed between higher vertical impacts and lower limb bone size and strength. INTRODUCTION: We investigated whether the benefit of habitual weight-bearing physical activity (PA) for lower limb bone strength in older women is explained by exposure to higher impacts, as previously suggested by observations in younger individuals. METHODS: Four hundred and eight women from the Cohort for Skeletal Health in Bristol and Avon (COSHIBA), mean 76.8 years, wore tri-axial accelerometers at the waist for a mean of 5.4 days. Y-axis peaks were categorised, using previously identified cutoffs, as low (0.5-1.0 g), medium (1.0-1.5 g), and higher (≥1.5 g) impacts. Mid and distal peripheral quantitative computed tomography scans of the tibia and radius were performed, as were hip and lumbar spine Dual X-ray Absorptiometry (DXA) scans. Regressions between (log transformed) number of low, medium and high impacts, and bone outcomes were adjusted for artefact error grade, age, height, fat and lean mass and impacts in other bands. RESULTS: Eight thousand eight hundred and nine (4047, 16,882) low impacts were observed during the measurement week, 345 (99, 764) medium impacts and 42 (17, 106) higher impacts (median with 25th and 75th quartiles). Higher vertical impacts were positively associated with lower limb bone strength as reflected by cross-sectional moment of inertia (CSMI) of the tibia [0.042 (0.012, 0.072) p = 0.01] and hip [0.067 (0.001, 0.133) p = 0.045] (beta coefficients show standard deviations change per doubling in impacts, with 95 % confidence interval). Higher impacts were positively associated with tibial periosteal circumference (PC) [0.015 (0.003, 0.027) p = 0.02], but unrelated to hip BMD. Equivalent positive associations were not seen for low or medium impacts. CONCLUSIONS: Despite their rarity, habitual levels of higher impacts were positively associated with lower limb bone size and strength, whereas equivalent relationships were not seen for low or medium impacts.

A novel accelerometer-based method to describe day-to-day exposure to potentially osteogenic vertical impacts in older adults: findings from a multi-cohort study.

This observational study assessed vertical impacts experienced in older adults as part of their day-to-day physical activity using accelerometry and questionnaire data. Population-based older adults experienced very limited high-impact activity. The accelerometry method utilised appeared to be valid based on comparisons between different cohorts and with self-reported activity. INTRODUCTION: We aimed to validate a novel method for evaluating day-to-day higher impact weight-bearing physical activity (PA) in older adults, thought to be important in protecting against osteoporosis, by comparing results between four cohorts varying in age and activity levels, and with self-reported PA levels. METHODS: Participants were from three population-based cohorts, MRC National Survey of Health and Development (NSHD), Hertfordshire Cohort Study (HCS) and Cohort for Skeletal Health in Bristol and Avon (COSHIBA), and the Master Athlete Cohort (MAC). Y-axis peaks (reflecting the vertical when an individual is upright) from a triaxial accelerometer (sampling frequency 50 Hz, range 0-16 g) worn at the waist for 7 days were classified as low (0.5-1.0 g), medium (1.0-1.5 g) or higher (≥1.5 g) impacts. RESULTS: There were a median of 90, 41 and 39 higher impacts/week in NSHD (age 69.5), COSHIBA (age 76.8) and HCS (age 78.5) participants, respectively (total n = 1512). In contrast, MAC participants (age 68.5) had a median of 14,322 higher impacts/week. In the three population cohorts combined, based on comparison of beta coefficients, moderate-high-impact activities as assessed by PA questionnaire were suggestive of stronger association with higher impacts from accelerometers (0.25 [0.17, 0.34]), compared with medium (0.18 [0.09, 0.27]) and low impacts (0.13 [0.07,0.19]) (beta coefficient, with 95 % CI). Likewise in MAC, reported moderate-high-impact activities showed a stronger association with higher impacts (0.26 [0.14, 0.37]), compared with medium (0.14 [0.05, 0.22]) and low impacts (0.03 [-0.02, 0.08]). CONCLUSIONS: Our new accelerometer method appears to provide valid measures of higher vertical impacts in older adults. Results obtained from the three population-based cohorts indicate that older adults generally experience very limited higher impact weight-bearing PA.

Discontinuation of contact precautions with the introduction of universal daily chlorhexidine bathing.

Contact precautions are a traditional strategy to prevent transmission of methicillin-resistant Staphylococcus aureus (MRSA). Chlorhexidine bathing is increasingly used to decrease MRSA burden and transmission in intensive care units (ICUs). We sought to evaluate a hospital policy change from routine contact precautions for MRSA compared with universal chlorhexidine bathing, without contact precautions. We measured new MRSA acquisition in ICU patients and surveyed for MRSA environmental contamination in common areas and non-MRSA patient rooms before and after the policy change. During the baseline and chlorhexidine bathing periods, the number of patients (453 vs. 417), ICU days (1999 vs. 1703) and MRSA days/1000 ICU days (109 vs. 102) were similar. MRSA acquisition (2/453 vs. 2/457, P = 0·93) and environmental MRSA contamination (9/474 vs. 7/500, P = 0·53) were not significantly different between time periods. There were 58% fewer contact precaution days in the ICU during the chlorhexidine period (241/1993 vs. 102/1730, P < 0·01). We found no evidence that discontinuation of contact precautions for patients with MRSA in conjunction with adoption of daily chlorhexidine bathing in ICUs is associated with increased MRSA acquisition among ICU patients or increased MRSA contamination of ICU fomites. Although underpowered, our findings suggest this strategy, which has the potential to reduce costs and improve patient safety, should be assessed in similar but larger studies.

Effect of powder oxidation on the impact toughness of electron beam melt Ti-6Al-4V.

Powder quality in additive manufacturing (AM) electron beam melt (EBM) of Ti-6Al-4V components is crucial in determining the critical material properties of the end item. In this study, we report on the effect of powder oxidation on the Charpy impact energy of Ti-6Al-4V parts manufactured using EBM. In addition to oxidation, the effects on impact energy due to hot isostatic pressing (HIP), specimen orientation, and EBM process defects were also investigated. This research has shown that excessive powder oxidation (oxygen mass fraction above 0.25 % and up to 0.46 %) dramatically decreases the impact energy. It was determined that the room temperature impact energy of the parts after excessive oxidation was reduced by about seven times. We also report that HIP post-processing significantly increases the impact toughness, especially for specimens with lower or normal oxygen content. The specimen orientation effect was found to be more significant for low oxidation levels.