Ground-Based Mobile Measurements to Track Urban Methane Emissions from Natural Gas in 12 Cities across Eight Countries.

To mitigate methane emission from urban natural gas distribution systems, it is crucial to understand local leak rates and occurrence rates. To explore urban methane emissions in cities outside the U.S., where significant emissions were found previously, mobile measurements were performed in 12 cities across eight countries. The surveyed cities range from medium size, like Groningen, NL, to large size, like Toronto, CA, and London, UK. Furthermore, this survey spanned across European regions from Barcelona, ES, to Bucharest, RO. The joint analysis of all data allows us to focus on general emission behavior for cities with different infrastructure and environmental conditions. We find that all cities have a spectrum of small, medium, and large methane sources in their domain. The emission rates found follow a heavy-tailed distribution, and the top 10% of emitters account for 60-80% of total emissions, which implies that strategic repair planning could help reduce emissions quickly. Furthermore, we compare our findings with inventory estimates for urban natural gas-related methane emissions from this sector in Europe. While cities with larger reported emissions were found to generally also have larger observed emissions, we find clear discrepancies between observation-based and inventory-based emission estimates for our 12 cities.

Priority setting for adult malnutrition and nutritional screening in healthcare: a James Lind Alliance.

BACKGROUND: Malnutrition is one the greatest global health challenges of our generation, leading to the increased utilisation of healthcare resources, as well as morbidity and mortality. Research has primarily been driven by industry, academia and clinical working groups and has had little involvement from patients and carers. The project described in the present study aimed to establish a priority setting partnership allowing patients, carers and healthcare professionals an opportunity to influence the research agenda. METHODS: A national survey was conducted to gather malnutrition uncertainties and identify key issues (i.e. areas within scope where an evidence-base is lacking) from those with experience of malnutrition. Uncertainties were analysed according to themes. Similar questions were grouped and summary questions were developed. A second survey was conducted and respondents were asked to choose their 10 most important summary questions. A workshop was conducted to finalise the top 10 research priorities from the most frequently indicated uncertainties on the interim survey. RESULTS: Overall, 1128 uncertainty questions were submitted from 268 people. The interim survey had 71 responses and a list of the top 26 questions was generated for the workshop. There were 26 questions discussed, ranked and agreed by healthcare professionals, carers and patients at the workshop. The top 10 research priorities were then chosen. These included questions on oral nutritional supplements, vulnerable groups, screening, community care, use of body mass index and technology. CONCLUSIONS: The top 10 research priorities in malnutrition and nutritional screening have been identified from a robust process involving patients, carers and healthcare professionals.

A novel discharge pathway for patients with advanced cancer requiring home parenteral nutrition.

BACKGROUND: The use of home parenteral nutrition (HPN) for palliative indications is increasing internationally and is the leading indication in some countries. Discharge on HPN can be complex in metabolically unstable patients and requires intestinal failure expertise. METHODS: Between 2012 and 2018, we performed a retrospective analysis aiming to assess the impact of a novel remote discharge pathway for palliative HPN patients. This was evaluated using a quality improvement approach. RESULTS: One hundred and twenty-five patients with active malignancy [mean (range) age 58 (25-80) years] were referred to the intestinal failure unit (IFU) for remote discharge. Of 82 patients were discharged from the oncology Centre on HPN using the pathway. The remaining 43 patients either declined HPN or the Oncology team felt that the patient became too unwell for HPN or died prior to discharge. There was an increase in patients referred for remote discharge from 13 in 2012 to 43 in 2017. The mean number of days between receipt of referral by the IFU to discharge on HPN from the oncology centre reduced from 29.4 days to 10.1 days. Following remote discharge, the mean number of days on HPN was 215.9 days. Catheter-related blood stream infection rates in this cohort were very low at 0.169 per 1000 catheter days. CONCLUSIONS: This is the first study to demonstrate the remote safe, effective and rapid discharge of patients requiring palliative HPN between two hospital sites. This allows patients with a short prognosis more time in their desired location.

Electroacoustic stimulation: now and into the future.

Cochlear implants have provided hearing to hundreds of thousands of profoundly deaf people around the world. Recently, the eligibility criteria for cochlear implantation have been relaxed to include individuals who have some useful residual hearing. These recipients receive inputs from both electric and acoustic stimulation (EAS). Implant recipients who can combine these hearing modalities demonstrate pronounced benefit in speech perception, listening in background noise, and music appreciation over implant recipients that rely on electrical stimulation alone. The mechanisms bestowing this benefit are unknown, but it is likely that interaction of the electric and acoustic signals in the auditory pathway plays a role. Protection of residual hearing both during and following cochlear implantation is critical for EAS. A number of surgical refinements have been implemented to protect residual hearing, and the development of hearing-protective drug and gene therapies is promising for EAS recipients. This review outlines the current field of EAS, with a focus on interactions that are observed between these modalities in animal models. It also outlines current trends in EAS surgery and gives an overview of the drug and gene therapies that are clinically translatable and may one day provide protection of residual hearing for cochlear implant recipients.

Development of a cell-based treatment for long-term neurotrophin expression and spiral ganglion neuron survival.

Spiral ganglion neurons (SGNs), the target cells of the cochlear implant, undergo gradual degeneration following loss of the sensory epithelium in deafness. The preservation of a viable population of SGNs in deafness can be achieved in animal models with exogenous application of neurotrophins such as brain-derived neurotrophic factor (BDNF) and neurotrophin-3. For translation into clinical application, a suitable delivery strategy that provides ongoing neurotrophic support and promotes long-term SGN survival is required. Cell-based neurotrophin treatment has the potential to meet the specific requirements for clinical application, and we have previously reported that Schwann cells genetically modified to express BDNF can support SGN survival in deafness for 4 weeks. This study aimed to investigate various parameters important for the development of a long-term cell-based neurotrophin treatment to support SGN survival. Specifically, we investigated different (i) cell types, (ii) gene transfer methods and (iii) neurotrophins, in order to determine which variables may provide long-term neurotrophin expression and which, therefore, may be the most effective for supporting long-term SGN survival in vivo. We found that fibroblasts that were nucleofected to express BDNF provided the most sustained neurotrophin expression, with ongoing BDNF expression for at least 30 weeks. In addition, the secreted neurotrophin was biologically active and elicited survival effects on SGNs in vitro. Nucleofected fibroblasts may therefore represent a method for safe, long-term delivery of neurotrophins to the deafened cochlea to support SGN survival in deafness.

Legionella pneumophila serogroup 3 infection: importance of serology.

We present a case of Legionella pneumophila serogroup 3 (LP3) infection in a patient with severe community-acquired pneumonia (CAP). The diagnosis was complicated by an initial equivocal L. pneumophila urinary antigen test, followed by two negative samples. LP3 was cultured from a sputum sample and the diagnosis was confirmed by serology 15 days into the admission. This case highlights the importance of considering non-LP1 serogroups as causes of CAP and the role of serological testing in diagnosis.

Effect of oxytocin on suppression of oestrus in mares exhibiting normal oestrous cycles.

AIM: To compare the efficacy of oxytocin given once daily, either I/V or I/M, on Days 7-14 post-ovulation, on the expression of oestrus in mares through to 65 days post-ovulation. METHODS: Eighteen mares of various breeds that were displaying normal oestrous cycles were randomly assigned to one of three treatment groups on the day of ovulation (Day 0), detected using transrectal ultrasonography. Mares in the control group (n = 6) were given 1 mL saline I/V; mares in the I/V and I/M groups (n = 6 per group) were injected with 10 IU oxytocin I/V and I/M, respectively. All treatments were given once daily on Days 7-14. Mares were teased by a stallion three times per week, up to 65 days post-ovulation, to detect oestrous or dioestrous behaviour. Ovarian follicular and luteal activity were monitored using transrectal ultrasonography three times weekly, and daily when a follicle >30 mm diameter was present until ovulation. Blood samples were collected weekly for analysis of concentrations of progesterone in serum. Prolonged dioestrus was defined as a period of >30 days of dioestrous behaviour after Day 0, confirmed by detection of corpora lutea and concentrations of progesterone in serum >4 nmol/L. RESULTS: Overall, 8/18 (44%) mares showed prolonged dioestrus. These included 2/6 (33%) mares in the control group, compared with 5/6 (83%) and 1/6 (16%) mares in the I/V and I/M groups, respectively (p = 0.11). The median duration of the first dioestrus was longer for the I/V group (64 (min 16, max 66) days) compared with the control group (18 (min 12, max 64) days) (p = 0.05), but was not different between the control group and the I/M group (16 (min 13, max 65) days) (p = 0.57). For all mares there was strong agreement between teasing behaviours, ultrasonographic assessment of ovarian activity, and concentration of progesterone in serum. CONCLUSIONS AND CLINICAL RELEVANCE: This study found that low doses of oxytocin did not increase the proportion of mares with prolonged dioestrus, compared with controls, although I/V oxytocin did increase the median duration of dioestrus. The results must be interpreted with some caution as group numbers were small, and a variety of breeds were used. Further investigation of oxytocin given I/V may be warranted as a potential method of oestrus suppression in mares exhibiting oestrous cycles that is low cost, safe and well-tolerated, and potentially reversible with prostaglandin.

Changes in subcellular localisation of MI-ER1 alpha, a novel oestrogen receptor-alpha interacting protein, is associated with breast cancer progression.

The oestrogen receptor-alpha (ER alpha) plays a key role in breast development and tumorigenesis and inhibiting its activity remains a prime strategy in the treatment of ER alpha-positive breast cancers. Thus, elucidation of the molecular mechanisms responsible for regulating ER alpha activity may facilitate the design of new, more effective breast cancer therapies. The MI-ER1 alpha is a novel transcriptional repressor that contains an LXXLL motif for interaction with nuclear hormone receptors. We investigated the ability of MI-ER1 alpha to bind to ER alpha in HEK293 and MCF-7 breast carcinoma cells, using co-immunoprecipitation assays. In both cell lines, MI-ER1 alpha interacted with ER alpha in the presence and absence of oestrogen, but the interaction was stronger in the absence of ligand. Functional analysis revealed that overexpression of MI-ER1 alpha in T47D breast carcinoma cells results in inhibition of oestrogen-stimulated anchorage-independent growth, suggesting that MI-ER1 alpha may play a role in regulating breast carcinoma cell proliferation in vivo. To explore this further, we performed an immunohistochemical analysis of normal breast tissue and breast carcinoma; a total of 110 cases were examined in whole tissue sections and 771 cases were analysed in tissue microarrays. No consistent difference in the MI-ER1 alpha expression level between normal breast tissue and breast carcinoma was discernible. However, there was a dramatic shift in the subcellular localisation: nuclear MI-ER1 alpha was detectable in 75% of normal breast samples and in 77% of hyperplasia, but in breast carcinoma, only 51% of DCIS, 25% of ILC and 4% of IDC contained nuclear staining. This shift from nuclear to cytoplasmic localisation of MI-ER1 alpha during breast cancer progression suggests that loss of nuclear MI-ER1 alpha might contribute to the development of invasive breast carcinoma.

Vitamin D and vitamin D analogues for preventing fractures associated with involutional and post-menopausal osteoporosis.

BACKGROUND: Vitamin D and related compounds have been used to prevent fractures. OBJECTIVES: To determine the effects of vitamin D or analogues, with or without calcium, in the prevention of fractures in older people. SEARCH STRATEGY: We searched the Cochrane Bone, Joint and Muscle Trauma Group trials register, the Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 1, 2005), MEDLINE, EMBASE, CINAHL, and reference lists of articles. Most recent search: March 2005. SELECTION CRITERIA: Randomised or quasi-randomised trials comparing vitamin D or an analogue, alone or with calcium, against placebo, no intervention, or calcium, reporting fracture outcomes, in older people. DATA COLLECTION AND ANALYSIS: Two authors independently assessed trial quality, and extracted data. Data were pooled, where admissible, using the fixed-effect model, or random-effects model if the relative risks were heterogeneous. MAIN RESULTS: Vitamin D alone showed no statistically significant effect on hip fracture (seven trials, 18,668 participants, RR 1.17, 95% CI 0.98 to 1.41), vertebral fracture (four trials, 5698 participants, RR (random effects) 1.13, 95% CI 0.50 to 2.55) or any new fracture (eight trials, 18,903 participants, RR 0.99, 95% CI 0.91 to 1.09). Vitamin D with calcium marginally reduced hip fractures (seven trials, 10,376 participants, RR 0.81, 95% CI 0.68 to 0.96), non-vertebral fractures (seven trials, 10,376 participants, RR 0.87, 95% CI 0.78 to 0.97), but there was no evidence of effect of vitamin D with calcium on vertebral fractures. The effect appeared to be restricted to those living in institutional care. Hypercalcaemia was more common when vitamin D or its analogues was given compared with placebo or calcium (14 trials, 8035 participants, RR 2.38, 95% CI 1.52 to 3.71). The risk was particularly high with calcitriol (three trials, 742 participants, RR 14.94, 95% CI 2.95 to 75.61). There was no evidence that vitamin D increased gastro-intestinal symptoms (seven trials, 10,188 participants, RR (random effects) 1.03, 95% CI 0.79 to 1.36) or renal disease (nine trials, 10,107 participants, RR 0.80, 95% CI 0.34 to 1.87). AUTHORS' CONCLUSIONS: Frail older people confined to institutions may sustain fewer hip and other non-vertebral fractures if given vitamin D with calcium supplements. Effectiveness of vitamin D alone in fracture prevention is unclear. There is no evidence of advantage of analogues of vitamin D compared with vitamin D. Calcitriol may be associated with an increased incidence of adverse effects. Dose, frequency, and route of administration of vitamin D in older people require further investigation.

Hip protectors for preventing hip fractures in older people.

BACKGROUND: Hip fracture in older people usually results from a fall on the hip. Hip protectors have been advocated as a means to reduce the risk of sustaining a hip fracture. OBJECTIVES: To determine if external hip protectors reduce the incidence of hip fractures in older people following a fall. SEARCH STRATEGY: We searched the Cochrane Musculoskeletal Injuries Group trials register (January 2005), the Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 1, 2005), MEDLINE (1966 to January Week 2, 2005), EMBASE (1988 to 2005 Week 02), CINAHL (1982 to December Week 2 2004), other databases and reference lists of relevant articles. We also contacted trialists. SELECTION CRITERIA: All randomised or quasi-randomised controlled trials comparing the use of hip protectors with a control group. DATA COLLECTION AND ANALYSIS: Two authors independently assessed trial quality and extracted data. We sought additional information from trialists. Pooling of uncorrected data from cluster-randomised trials was only done on an exploratory basis. MAIN RESULTS: Fifteen included trials contributed data to this updated review. One trial, which was a study of compliance (adherence) lasting 12 weeks, contributed no fracture outcome data. Pooling of data from eleven trials conducted in nursing or residential care settings, including six cluster-randomised studies, showed evidence of a marginally statistically significant reduction in hip fracture incidence (relative risk (RR) 0.77, 95% confidence interval (CI) 0.62 to 0.97). This analysis showed significant statistical heterogeneity. Pooling of data from three individually randomised trials involving 5135 community dwelling participants, showed no reduction in hip fracture incidence from the provision of hip protectors (RR 1.16, 95% CI 0.85 to 1.59). There was no evidence of any significant effect of hip protectors on incidence of pelvic or other fractures. No important adverse effects of the hip protectors were reported but compliance, particularly in the long term, was poor. AUTHORS' CONCLUSIONS: Accumulating evidence casts some doubt on the effectiveness of the provision of hip protectors in reducing the incidence of hip in older people. Acceptance and adherence by users of the protectors remain poor due to discomfort and practicality.

Hip protectors for preventing hip fractures in the elderly.

BACKGROUND: Hip fracture in the elderly usually results from a fall on the hip. Hip protectors have been advocated as a means to reduce the risk of sustaining a hip fracture. OBJECTIVES: To determine if external hip protectors reduce the incidence of hip fractures in elderly persons following a fall. SEARCH STRATEGY: We searched the Cochrane Musculoskeletal Injuries Group trials register (February 2004), the Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 1, 2004), MEDLINE (1966 to February Week 2 2004), EMBASE (1988 to 2004 Week 08), CINAHL (1982 to February Week 2 2004), other databases and reference lists of relevant articles. We also contacted trialists. SELECTION CRITERIA: All randomised or quasi-randomised controlled trials comparing the use of hip protectors with a control group. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trial quality and extracted data. We sought additional information from all trialists. MAIN RESULTS: An additional trial with 4169 participants was included in this update, giving a total of 14 included trials. One, which was a study of compliance (adherence) lasting 12 weeks, contributed no fracture outcome data. Five studies involving 4316 participants were cluster randomised by care unit, nursing home or nursing home ward rather than by the individual. Each of these studies reported a reduced incidence of hip fractures within those units allocated to receive the protectors. Because the majority of these trials had not been analysed to allow for clustering, pooling of their results was not undertaken. Pooling of data from five individually randomised trials conducted in nursing/residential care settings (1426 participants) showed no significant reduction in hip fracture incidence (hip protectors 37/822, controls 40/604, relative risk (RR) 0.83, 95% confidence interval (CI) 0.54 to 1.29). Three individually randomised trials of 5135 community dwelling participants, reported no reduction in hip fracture incidence with the hip protectors (RR 1.16, 95% CI 0.85 to 1.59). No important adverse effects of the hip protectors were reported but compliance, particularly in the long term, was poor. REVIEWERS' CONCLUSIONS: There is no evidence of effectiveness of hip protectors from studies in which randomisation was by individual patient within an institution, or for those living in their own homes. Data from cluster randomised studies indicate that, for those living in institutional care with a high background incidence of hip fracture, a programme of providing hip protectors appears to reduce the incidence of hip fractures. Acceptability by users of the protectors remains a problem, due to discomfort and practicality.

The use of PCR to detect Neospora caninum DNA in the blood of naturally infected cows.

Twelve 2-year old heifers in their fifth month of gestation when pregnancy tested were used in this study. Six heifers aborted at approximately 4 months of gestation and had blood samples drawn less than 6 weeks after the abortions were identified. Blood samples were also drawn from three sero-positive pregnant and three sero-negative pregnant heifers. DNA was isolated from the samples and a 350 bp fragment of the Nc-5 gene was PCR amplified using primer pair Np21+ and Np6+. Also, the Internal Transcribed Spacer 1 (ITS1) was PCR amplified using Tim 3 and Tim 11 primer pair. The Nc-5 gene fragment was cloned, sequenced and the sequence BLAST-tested. Similarly, the ITS1 product was sequenced and BLAST-tested. The BLAST test results revealed that Neospora caninum DNA was present in these blood samples indicating that polymerase chain reaction can be used in the detection of N. caninum DNA in the blood of sero-positive cows.

Acinar dysplasia: a rare cause of neonatal respiratory failure.

UNLABELLED: Acinar dysplasia is a rare cause of death in the first few hours of life, due to an absence of alveoli. This report presents the first case associated with additional major renal malformations. The diagnosis of acinar dysplasia was unexpectedly made at autopsy. CONCLUSION: Even in the presence of antenatally diagnosed severe anomalies, autopsy may reveal diagnostically important information.

Isolation and molecular characterisation of Neospora caninum in cattle in New Zealand.

AIM: To isolate Neospora caninum from the brains of naturally infected cattle and use molecular techniques to characterise the isolates. METHODS: Neospora caninum tachyzoites were isolated in Vero cell culture from the brains of a cow and two calves. The isolates were characterised using polymerase chain reaction (PCR) methods, DNA sequencing, an immunofluorescent antibody test (IFAT), transmission electron microscopy (TEM), and immunohistochemistry (IHC). The brains of the three cattle were subjected to histopathological examination. A pathogenicity study was conducted in 120 BALB/c mice. RESULTS: Neospora caninum tachyzoites were isolated from all three cases and first observed in vitro between 14 and 17 days post-inoculation. Parasites were sub-cultured and maintained in Vero cell culture for more than 6 months. PCR products were generated for all three isolates, using two different primers. Sequencing of the PCR products and a subsequent BLAST search identified the isolates as N. caninum. In addition, the isolates tested positive using IFAT and IHC, and ultrastructure revealed by TEM was characteristic of N. caninum. Histopathological examination revealed lesions characteristic of N. caninum in 1/3 brains. In the pathogenicity study using BALB/c mice, the mortality rate was 3-7%. CONCLUSION: This was the first successful isolation of N. caninum in New Zealand confirmed using molecular characterisation tests.

Interventions for preventing falls in elderly people.

BACKGROUND: Approximately 30 per cent of people over 65 years of age and living in the community fall each year; the number is higher in institutions. Although less than one fall in 10 results in a fracture, a fifth of fall incidents require medical attention. OBJECTIVES: To assess the effects of interventions designed to reduce the incidence of falls in elderly people (living in the community, or in institutional or hospital care). SEARCH STRATEGY: We searched the Cochrane Musculoskeletal Group specialised register (January 2003), Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 1, 2003), MEDLINE (1966 to February 2003), EMBASE (1988 to 2003 Week 19), CINAHL (1982 to April 2003), The National Research Register, Issue 2, 2003, Current Controlled Trials (www.controlled-trials.com accessed 11 July 2003) and reference lists of articles. No language restrictions were applied. Further trials were identified by contact with researchers in the field. SELECTION CRITERIA: Randomised trials of interventions designed to minimise the effect of, or exposure to, risk factors for falling in elderly people. Main outcomes of interest were the number of fallers, or falls. Trials reporting only intermediate outcomes were excluded. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trial quality and extracted data. Data were pooled using the fixed effect model where appropriate. MAIN RESULTS: Sixty two trials involving 21,668 people were included. Interventions likely to be beneficial: Multidisciplinary, multifactorial, health/environmental risk factor screening/intervention programmes in the community both for an unselected population of older people (4 trials, 1651 participants, pooled RR 0.73, 95%CI 0.63 to 0.85), and for older people with a history of falling or selected because of known risk factors (5 trials, 1176 participants, pooled RR 0.86, 95%CI 0.76 to 0.98), and in residential care facilities (1 trial, 439 participants, cluster-adjusted incidence rate ratio 0.60, 95%CI 0.50 to 0.73) A programme of muscle strengthening and balance retraining, individually prescribed at home by a trained health professional (3 trials, 566 participants, pooled relative risk (RR) 0.80, 95% confidence interval (95%CI) 0.66 to 0.98) Home hazard assessment and modification that is professionally prescribed for older people with a history of falling (3 trials, 374 participants, RR 0.66, 95% CI 0.54 to 0.81) Withdrawal of psychotropic medication (1 trial, 93 participants, relative hazard 0.34, 95%CI 0.16 to 0.74) Cardiac pacing for fallers with cardioinhibitory carotid sinus hypersensitivity (1 trial, 175 participants, WMD -5.20, 95%CI -9.40 to -1.00) A 15 week Tai Chi group exercise intervention (1 trial, 200 participants, risk ratio 0.51, 95%CI 0.36 to 0.73). Interventions of unknown effectiveness: Group-delivered exercise interventions (9 trials, 1387 participants) Individual lower limb strength training (1 trial, 222 participants) Nutritional supplementation (1 trial, 46 participants) Vitamin D supplementation, with or without calcium (3 trials, 461 participants) Home hazard modification in association with advice on optimising medication (1 trial, 658 participants), or in association with an education package on exercise and reducing fall risk (1 trial, 3182 participants) Pharmacological therapy (raubasine-dihydroergocristine, 1 trial, 95 participants) Interventions using a cognitive/behavioural approach alone (2 trials, 145 participants) Home hazard modification for older people without a history of falling (1 trial, 530 participants) Hormone replacement therapy (1 trial, 116 participants) Correction of visual deficiency (1 trial, 276 participants). Interventions unlikely to be beneficial: Brisk walking in women with an upper limb fracture in the previous two years (1 trial, 165 participants). REVIEWER'S CONCLUSIONS: Interventions to prevent falls that are likely to be effective are now available; less is known about their effectiveness in preventing fall-related injuries. Costs per fall prevented have been established for four of the interventions and careful economic modelling in the context of the local healthcare system is important. Some potential interventions are of unknown effectiveness and further research is indicated.

Hip protectors for preventing hip fractures in the elderly.

BACKGROUND: Hip fracture in the elderly is usually the result of a simple fall. Hip protectors have been advocated as a means to reduce the risk of sustaining a fracture in a fall on the hip. OBJECTIVES: To determine if external hip protectors reduce the incidence of hip fractures in elderly persons following a fall. SEARCH STRATEGY: We searched the Cochrane Musculoskeletal Injuries Group trials register (April 2003), the Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 1, 2003), MEDLINE (1966 to April 2003), EMBASE (1988 to 2003 week 14), CINAHL (1982 to April 2003) and reference lists of relevant articles. Trialists were contacted, and ongoing trials identified in The National Research Register (http://www.update-software.com/national/ accessed 20/01/03) and Current Controlled Trials (http://controlled-trials.com/ accessed 20/01/03). SELECTION CRITERIA: All randomised or quasi-randomised controlled trials (RCTs) comparing the use of hip protectors with a control group. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trial quality, using a 10-item scale, and extracted data. Additional information was sought from all trialists. Wherever appropriate and possible, the data are presented graphically. MAIN RESULTS: In this third update, 13 randomised controlled trials were included. One, which was a study of compliance lasting 12 weeks, contributed no fracture outcome data. Five studies involving 4316 participants were cluster randomised by care unit, nursing home or nursing home ward rather than by the individual. Individually, each of these studies reported a reduced incidence of hip fractures within those units allocated to receive the protectors. Because of the use of cluster randomisation pooling of results of these studies was not undertaken. Pooling of data from five individually randomised trials conducted in nursing/residential care settings (1426 participants) showed no significant reduction in hip fracture incidence (hip protectors 37/822, controls 40/604, RR 0.83, 95% CI 0.54 to 1.29). Two individually randomised trials of 966 community dwelling participants, reported no reduction in hip fracture incidence with the hip protectors (RR 1.11, 95% CI 0.65 to 1.90). No important adverse effects of the hip protectors were reported but compliance, particularly in the long term, was poor. REVIEWER'S CONCLUSIONS: There is no evidence of effectiveness of hip protectors from studies in which randomisation was by individual patient within an institution, or for those living in their own homes. Data from cluster randomised studies indicates that, for those living in institutional care with a high background incidence of hip fracture, a programme of providing hip protectors appears to reduce the incidence of hip fractures. Acceptability by users of the protectors remains a problem, due to discomfort and practicality. Cost effectiveness remains unclear.

Interventions for preventing falls in elderly people.

BACKGROUND: Approximately 30 per cent of people over 65 years of age and living in the community fall each year; the number is higher in institutions. Although less than one fall in 10 results in a fracture, a fifth of fall incidents require medical attention. OBJECTIVES: To assess the effects of interventions designed to reduce the incidence of falls in elderly people (living in the community, or in institutional or hospital care). SEARCH STRATEGY: We searched the Cochrane Musculoskeletal Group specialised register (January 2001), Cochrane Controlled Trials Register (The Cochrane Library, Issue 1, 2001), MEDLINE (1966 to February 2001), EMBASE (1988 to 2001 Week 14), CINAHL (1982 to March 2001), The National Research Register, Issue 1, 2001, Current Controlled Trials (www.controlled-trials.com accessed 25 May 2001), and reference lists of articles. We also contacted researchers in the field. SELECTION CRITERIA: Randomised trials of interventions designed to minimise the effect of, or exposure to, risk factors for falling in elderly people. Main outcomes of interest were the number of fallers, or falls. Trials reporting only intermediate outcomes were excluded. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trial quality and extracted data. Data were pooled using the fixed effect model where appropriate. MAIN RESULTS: Interventions likely to be beneficial: ~bullet~A programme of muscle strengthening and balance retraining, individually prescribed at home by a trained health professional (3 trials, 566 participants, pooled relative risk (RR) 0.80, 95% confidence interval (95%CI) 0.66 to 0.98). ~bullet~A 15 week Tai Chi group exercise intervention (1 trial, 200 participants, risk ratio 0.51, 95%CI 0.36 to 0.73). ~bullet~Home hazard assessment and modification that is professionally prescribed for older people with a history of falling (1 trial, 530 participants, RR 0.64, 95% CI 0.49 to 0.84). A reduction in falls was seen both inside and outside the home. ~bullet~Withdrawal of psychotropic medication (1 trial, 93 participants, relative hazard 0.34, 95%CI 0.16 to 0.74). ~bullet~Multidisciplinary, multifactorial, health/environmental risk factor screening/intervention programmes, both for unselected community dwelling older people (data pooled from 3 trials, 1973 participants, pooled RR 0.73, 95%CI 0.63 to 0.86), and for older people with a history of falling, or selected because of known risk factors (data pooled from 2 trials, 713 participants, pooled RR 0.79, 95%CI 0.67 to 0.94). Interventions of unknown effectiveness: ~bullet~Group-delivered exercise interventions (9 trials, 2177 participants). ~bullet~Nutritional supplementation (1 trial, 50 participants). ~bullet~Vitamin D supplementation, with or without calcium (3 trials, 679 participants). ~bullet~Home hazard modification in association with advice on optimising medication (1 trial, 658 participants), or in association with an education package on exercise and reducing fall risk (1 trial, 3182 participants). ~bullet~Pharmacological therapy (raubasine-dihydroergocristine, 1 trial, 95 participants). ~bullet~Fall prevention programmes in institutional settings. ~bullet~Interventions using a cognitive/behavioural approach alone (2 trials, 145 participants). ~bullet~Home hazard modification for older people without a history of falling (1 trial, 530 participants). ~bullet~ Hormone replacement therapy (1 trial, 116 participants). Interventions unlikely to be beneficial: ~bullet~Brisk walking in women with an upper limb fracture in the previous two years (1 trial, 165 participants). REVIEWER'S CONCLUSIONS: Interventions to prevent falls that are likely to be effective are now available; less is known about their effectiveness in preventing fall-related injuries. Costs per fall prevented have been established for four of the interventions and careful economic modelling in the context of the local healthcare system is important. Some potential interventions are of unknown effectiveness and further research is indicated.

Nuclear localization signals in the Xenopus FGF embryonic early response 1 protein.

Xenopus early response 1 (XER1) is a fibroblast growth factor-inducible transcription factor whose developmentally regulated nuclear localization is thought to be important in the control of cell differentation during embryonic development [Luchman et al., Mech. Dev. 80 (1999) 111-114]. Analysis of the XER1 amino acid sequence revealed four regions which contain potential nuclear localization sequences (NLSs). Using mutant XER1 proteins and portions of XER1 fused to green fluorescent protein (GFP) transfected into NIH 3T3 cells, we have determined that only one of these, NLS4, located near the carboxy-terminus of XER1, is necessary and sufficient for targeting exclusively to the nucleus. Of the other three predicted NLS sequences, only NLS1, consisting of the sequence (138)RPRRCK(143) was shown to function as a cryptic, weak NLS. NLS4 contains a core region consisting of the sequence (463)RPIKRQRMD(471) which is similar to the core NLS directing the human c-MYC protein to the nucleus. The core sequence is flanked by a predicted cdc2/protein kinase A phosphorylation motif, however mutation of the serine(472) to alanine or aspartic acid had no detectable effect on accumulation of GFP-XER1 fusion proteins in the nucleus, demonstrating that this putative phosphorylation site plays no role in regulating nuclear transport.