Minimum indoor temperature threshold recommendations for English homes in winter - A systematic review.

OBJECTIVES: To identify and assess the available evidence on the impacts of cold indoor temperature thresholds on human health and make evidence-based recommendations for English homes. STUDY DESIGN: Systematic literature review. METHODS: A systematic search of peer-reviewed published literature from the UK and countries with similar climates, and grading of the evidence using the National Institute of Health (NIH) framework was followed by a discussion with experts and formulation of recommendations. RESULTS: Twenty papers were included. Studies were included if they were conducted outside England but were from countries considered to have similar climates. Studies included two small randomised controlled trials, two cohort studies and one case control study; other studies were cross-sectional, largely laboratory-based studies. Health effects in the general population start to occur at around 18 °C. Effects in older people are more profound than in younger adults. Older people are less able to perceive low temperatures. DISCUSSION: Although evidence was limited, a strong argument for setting thresholds remains. The effects observed on the general population and the effects on those more vulnerable makes a case for a recommended minimum temperature for all. Health messages should be clear and simple, allowing informed choices to be made. A threshold of 18 °C was considered the evidence based and practical minimum temperature at which a home should be kept during winter in England. CONCLUSION: There is limited evidence available on minimum temperature thresholds for homes. However a recommendation of at least 18 °C for the whole population with nuancing of messages for those more vulnerable to the effects of cold can be made from the results of the retrieved studies. RECOMMENDATION: Heating homes to at least 18 °C (65 °F) in winter poses minimal risk to the health of a sedentary person, wearing suitable clothing.

Impaired sodium-evoked paraventricular nucleus neuronal activation and blood pressure regulation in conscious Sprague-Dawley rats lacking central Gαi2 proteins.

AIM: We determined the role of brain Gαi2 proteins in mediating the neural and humoral responses of conscious male Sprague-Dawley rats to acute peripheral sodium challenge. METHODS: Rats pre-treated (24-h) intracerebroventricularly with a targeted oligodeoxynucleotide (ODN) (25 µg per 5 µL) to downregulate brain Gαi2 protein expression or a scrambled (SCR) control ODN were challenged with an acute sodium load (intravenous bolus 3 m NaCl; 0.14 mL per 100 g), and cardiovascular parameters were monitored for 120 min. In additional groups, hypothalamic paraventricular nucleus (PVN) Fos immunoreactivity was examined at baseline, 40, and 100 min post-sodium challenge. RESULTS: In response to intravenous hypertonic saline (HS), no difference was observed in peak change in mean arterial pressure between groups. In SCR ODN pre-treated rats, arterial pressure returned to baseline by 100 min, while it remained elevated in Gαi2 ODN pre-treated rats (P < 0.05). No difference between groups was observed in sodium-evoked increases in Fos-positive magnocellular neurons or vasopressin release. V1a receptor antagonism failed to block the prolonged elevation of arterial pressure in Gαi2 ODN pre-treated rats. A significantly greater number of Fos-positive ventrolateral parvocellular, lateral parvocellular, and medial parvocellular neurons were observed in SCR vs. Gαi2 ODN pre-treated rats at 40 and 100 min post-HS challenge (P < 0.05). In SCR, but not Gαi2 ODN pre-treated rats, HS evoked suppression of plasma norepinephrine (P < 0.05). CONCLUSION: This highlights Gαi2 protein signal transduction as a novel central mechanism acting to differentially influence PVN parvocellular neuronal activation, sympathetic outflow, and arterial pressure in response to acute HS, independently of actions on magnocellular neurons and vasopressin release.

The distribution of CY2PC19*2 allele in a Trinidadian population. Is Clopidogrel the right choice?

OBJECTIVE: To determine the distribution of the CYP2C19*2 allele among Trinidadians. DESIGN AND METHODS: This is a cross sectional study among 100 patients attending primary health centers within the North Central Region of Trinidad. A stratified sampling technique was used in which there were three mutually exclusive subgroups: those of South Asian descent (Indo-Trinidadians), African descent (Afro-Trinidadians) and mixed ethnicity. Subsequently, systematic sampling was applied to each stratum to improve the representativeness of the sample. Hence, the 100 subjects recruited for the study were 40 Indo-Trinidadians, 40 Afro-Trinidadians and 20 of mixed descent. Apart from baseline data which included age, gender and ethnicity, DNA was assessed for the CYP2C19*2 allelic variant using a PCR method. RESULTS: There was a high allelic frequency (37%) for CYP2C19*2 which was found to be more common among Indo-Trinidadians (47.5%, 95% CI 32.0-63.0) compared to Afro-Trinidadians (22.5%, 95% CI 9.6-35.4) or people of mixed origin (45%, 95% CI 23.2-66.8). There was a significant difference (p=0.019) between CYP2C19*2 frequencies for Indo-Trinidadians and Afro-Trinidadians. CONCLUSION: We provided evidence that the prevalence of CYP2C19*2 mutation was high in our setting.

The Cold Weather Plan evaluation: an example of pragmatic evidence-based policy making?

OBJECTIVES: An evaluation of the Cold Weather Plan (CWP) for England 2011-2012 was undertaken in April 2012 to generate the basis for further revisions. It is widely considered good practice to formulate and revise policy on the basis of the best available evidence. This paper examines whether the evaluation is an example of pragmatic evidence-based policy-making. STUDY DESIGN: A process evaluation with a formative multimethods approach. METHODS: An electronic survey and national workshop were conducted alongside the production of a number of summary reports from the Health Protection Agency surveillance systems and Met Office meteorological data. The Department of Health and the Met Office were consulted on how the evaluation recommendations shaped the revised CWP and Met Office Cold Weather Alerting System respectively. RESULTS: The Cold Weather Plan survey had 442 responses, a majority from Local Authorities, and from all regions of England. Thematic analysis generated qualitative data, which along with feedback from the workshop were synthesized into six main recommendations. Reviewing the new CWP and the Met Office Cold Weather Alerting System revealed significant modifications on the basis of the evaluation. CONCLUSIONS: The evaluation sets the context for cold weather and health during the 2011-2012 winter. This study shows that the CWP 2012-2013 was revised on the basis of the national evaluation recommendations and is an example of pragmatic evidence-based policy-making.

Using an Emergency Department Syndromic Surveillance System to investigate the impact of extreme cold weather events.

This report describes the development of novel syndromic cold weather public health surveillance indicators for use in monitoring the impact of extreme cold weather on attendances at EDs, using data from the 2010-11 and 2011-12 winters. A number of new surveillance indicators were created specifically for the identification and monitoring of cold weather related ED attendances, using the diagnosis codes provided for each attendance in the Emergency Department Syndromic Surveillance System (EDSSS), the first national syndromic surveillance system of its kind in the UK. Using daily weather data for the local area, a time series analysis to test the sensitivity of each indicator to cold weather was undertaken. Diagnosis codes relating to a health outcome with a potential direct link to cold weather were identified and assigned to a number of 'cold weather surveillance indicators'. The time series analyses indicated strong correlations between low temperatures and cold indicators in nearly every case. The strongest fit with temperature was cold related fractures in females, and that of snowfall was cold related fractures in both sexes. Though currently limited to a small number of sentinel EDs, the EDSSS has the ability to give near real-time detail on the magnitude of the impact of weather events. EDSSS cold weather surveillance fits well with the aims of the Cold Weather Plan for England, providing information on those particularly vulnerable to cold related health outcomes severe enough to require emergency care. This timely information aids those responding to and managing the effects on human health, both within the EDs themselves and in the community as a whole.

Warm Homes, Healthy People Fund 2011/12: a mixed methods evaluation.

OBJECTIVES: To assess how the Warm Homes Healthy People Fund 2011/12 was used by English local authorities and their partners to tackle excess winter mortality. STUDY DESIGN: Mixed-methods evaluation. METHODS: Three sources of data were used: an online survey to local authority leads, document analysis of local evaluation reports and telephone interviews of local leads. These were analysed to provide numerical estimates, key themes and case studies. RESULTS: There was universal approval of the fund, with all survey respondents requesting the fund to continue. An estimated 130,000 to 200,000 people in England (62% of them elderly) received a wide range of interventions, including structural interventions (such as loft insulation), provision of warm goods and income maximization. Raising awareness was another component, with all survey respondents launching a local media campaign. Strong local partnerships helped to facilitate the implementation of projects. The speed of delivery may have resulted in less strategic targeting of the most vulnerable residents. CONCLUSIONS: The Fund was popular and achieved much in winter 2011/2012, although its impact on cold-related morbidity and mortality is unknown.

Traumatic stress reactivity promotes excessive alcohol drinking and alters the balance of prefrontal cortex-amygdala activity.

Post-traumatic stress disorder (PTSD) and alcoholism are highly comorbid in humans and have partially overlapping symptomatic profiles. The aim of these studies was to examine the effects of traumatic stress (and stress reactivity) on alcohol-related behaviors and neuronal activation patterns. Male Wistar rats were trained to respond for alcohol, were exposed to predator odor (bobcat urine) paired with context and were tested for short- and long-term avoidance of the predator odor-paired context, alcohol self-administration and compulsivity of alcohol responding. Rats were re-exposed to the odor-paired context for western blot analysis of ERK phosphorylation in subregions of the medial prefrontal cortex (mPFC) and the amygdala. Rats that avoided the predator-paired chamber (Avoiders) exhibited persistent avoidance up to 6 weeks post conditioning. Avoiders exhibited increases in operant alcohol responding over weeks, as well as more compulsive-like responding for alcohol adulterated with quinine. Following re-exposure to the predator odor-paired context, Avoiders and Non-Avoiders exhibited unique patterns of neuronal activation in subregions of the mPFC and the amygdala, which were correlated with changes in avoidance and alcohol drinking. Furthermore, activity of upstream regions was differentially predictive of downstream regional activity in the Avoiders versus Non-Avoiders. An animal model for assessing the effect of traumatic stress on alcohol drinking reveals individual differences in neuronal activation patterns associated with re-exposure to traumatic stress-related stimuli, and may provide insight into the neural mechanisms underlying excessive alcohol consumption in humans with PTSD.

Transgenic, inducible RNAi in megakaryocytes and platelets in mice.

BACKGROUND: RNA interference (RNAi) is a powerful tool for suppressing gene function. The tetracycline (tet)-regulated expression system has recently been adapted to allow inducible RNAi in mice, however its efficiency in a particular cell type in vivo depends on a transgenic tet transactivator expression pattern and is often highly variable. OBJECTIVE: We aimed to establish a transgenic strategy that allows efficient and inducible gene knockdown in particular hematopoietic lineages in mice. METHODS AND RESULTS: Using a tet-regulated reporter gene strategy, we found that transgenic mice expressing the rtTA (tet-on) transactivator under control of the cytomegalovirus (CMV) promoter (CMV-rtTA mice) display inducible reporter gene expression with unusual and near-complete efficiency in megakaryocytes and platelets. To test whether the CMV-rtTA transgene can drive inducible and efficient gene knockdown within this lineage, we generated a novel mouse strain harboring a tet-regulated short hairpin RNA (shRNA) targeting Bcl-x(L) , a pro-survival Bcl-2 family member known to be essential for maintaining platelet survival. Doxycycline treatment of adult mice carrying both transgenes induces shRNA expression, depletes Bcl-x(L) in megakaryocytes and triggers severe thrombocytopenia, whereas doxycycline withdrawal shuts off shRNA expression, normalizes Bcl-x(L) levels and restores platelet numbers. These effects are akin to those observed with drugs that target Bcl-x(L) , clearly demonstrating that this transgenic system allows efficient and inducible inhibition of genes in megakaryocytes and platelets. CONCLUSIONS: We have established a novel transgenic strategy for inducible gene knockdown in megakaryocytes and platelets that will be useful for characterizing genes involved in platelet production and function in adult mice.

Microvascular responses following digital thermal hyperaemia and iontophoresis measured by laser Doppler imaging in idiopathic inflammatory myopathy.

OBJECTIVE: To measure microvascular function using laser Doppler imaging following digital hyperaemia and iontophoresis of vasoactive substances in patients with idiopathic inflammatory myopathy (IIM). METHODS: Fifteen patients with IIM including eight patients with dermatomyositis (DM) and seven patients with polymyositis (PM) were studied. Fifteen age-matched normal controls were also recruited. Scanning red laser Doppler imaging (LDI) was performed after resting the subject in a temperature controlled room at 23 degrees C for 20 min. An initial LDI scan was performed to assess baseline blood flow. Digital microvascular responses were quantified following a maximum hyperaemic response (MHR) and iontophoresis with endothelial dependent acetylcholine (Ach) and endothelial independent sodium nitroprusside (SNP). Maximum vasodilation following iontophoresis was expressed as a percentage of the MHR. RESULTS: All subjects were age matched, and the duration of disease was similar between the IIM patients. There was no significant difference in baseline blood flow when comparing the three study groups. There was no significant difference in MHR or SNP/MHR when comparing DM or PM with controls. However, Ach/MHR was significantly lower in both the DM and PM group compared with controls (both P < 0.01). There was no significant difference in any of the microvascular responses when comparing patients with DM directly with PM. CONCLUSION: This is the first study to evaluate microvascular responses using LDI in patients with IIM. We have demonstrated that patients with DM have abnormal endothelial dependent mediated vasodilation and the same abnormality is present in patients with PM.

Maximum blood flow and microvascular regulatory responses in systemic sclerosis.

Objectives. To investigate microvascular function using laser Doppler imaging (LDI) following response to hyperaemia, neurovascular reflex and iontophoresis in systemic sclerosis (SSc) in comparison with primary Raynaud's phenomenon (PRP) and age-matched controls. A secondary aim was to evaluate if SSc patients with a higher Medsger vascular score have lower endothelial responses. Methods. Twenty patients with SSc, 10 PRP and 17 controls were studied. Patients with SSc were scored using the vascular component of the Medsger severity scale. A baseline LDI scan was performed on the dorsal aspect of both hands. Digital responses were quantified following maximum hyperaemic response (MHR), contralateral vasoconstrictor response (CLVc) and iontophoresis with acetylcholine (Ach)-endothelial dependent and sodium nitroprusside (SNP)-endothelial independent. Mean blood flow was quantified over a standard region of interest. Results. MHR was lower in SSc patients compared with controls (P < 0.001). A similar trend was seen when comparing SSc with PRP although this did not reach significance (P = 0.07). CLVc and Ach/MHR were lower in SSc vs PRP (P < 0.05) and controls (P < 0.001). No difference was observed in MHR, CLVc and Ach/MHR between PRP and controls. Overall, SNP/MHR was similar in all the three groups. SSc patients with a higher Medsger vascular score had lower endothelial-dependent (P < 0.01) and independent (P < 0.05) responses. Conclusion. SSc patients have abnormal microvascular regulatory responses compared with PRP and controls. This study also suggests that the degree of endothelial dysfunction may be related to the degree of peripheral vascular involvement.

The clinical and genetic associations of anti-cyclic citrullinated peptide antibodies in psoriatic arthritis.

OBJECTIVES: Antibodies recognizing a cyclic citrullinated peptide (anti-CCP) are highly specific for rheumatoid arthritis (RA) but their role in psoriatic arthritis (PsA) remains unclear. The aim of this study was therefore to investigate the prevalence of anti-CCP antibodies in PsA and assess their clinical and genetic associations. METHODS: One hundred and twenty-six patients with PsA, 40 patients with seropositive RA and 40 controls were tested for the presence of anti-CCP antibodies, rheumatoid factor (RF) and the HLA-DRB1 shared epitope. Clinical and radiological data were collected prospectively on all patients and compared between anti-CCP-positive and -negative patients. RESULTS: Seven (5.6%) patients with PsA were positive for anti-CCP antibodies compared with 0% of controls and 97% of patients with seropositive RA. The presence of anti-CCP antibodies in PsA was significantly associated with the HLA-DRB1 shared epitope (P<0.005), erosive disease (P<0.05), number of swollen joints (P<0.02) and DMARD use (P<0.05). CONCLUSIONS: Overall, the increased prevalence of anti-CCP antibodies in this PsA population failed to reach statistical significance. However, when present, they were a marker of disease severity and had RA-linked MHC class II associations. Further studies are needed in a larger population of patients with PsA and appropriate controls to confirm any true association that may be present.

Joint and soft tissue injections: a survey of general practitioners.

OBJECTIVES: To determine the type of joint and soft tissue injections carried out by general practitioners (GPs) in the Bath area and factors affecting activity. METHODS: A questionnaire was sent to 360 GPs requesting information on injections carried out during the previous 12 months, referral pathways for injection, barriers to injecting and training. RESULTS: We received 251 replies. The commonest injections were for tennis elbow, glenohumeral joint, knee, supraspinatus tendonitis and carpal tunnel. The majority of GPs (66.4%) carry out most injections themselves, 26.3% refer to a colleague and 7.3% refer to secondary care. Over half (51%) of all the injections are carried out by 15.6% of the GPs. Factors associated with higher levels of injection activity were: male gender, partnership, more than 10 years' experience, a special interest in rheumatology or orthopaedics and working in a rural or mixed practice. The most important barriers to carrying out injections were lack of practical training, lack of confidence and inability to maintain skills. Most GPs have been trained on models. CONCLUSIONS: Most GPs carry out some joint and soft tissue injections, but limit themselves to knees, shoulders and elbows. A small highly active group receive referrals from colleagues. Gender and specialist training strongly influence activity. Many, especially female and part-time, GPs find it hard to maintain their skills and confidence. Training targeted at this group, based in practices and using models and other tools, is likely to increase the number of patients receiving timely injections in general practice.

Prior knowledge and exemplar encoding in children's concept acquisition.

Three experiments examined how children's domain knowledge and observation of exemplars interact during concept acquisition and how exposure to novel exemplars causes revision of such knowledge. In Experiments 1 (N = 126) and 2 (N = 64), children aged 4 to 10 years were shown exemplars of fictitious animal categories that were either unrelated to, or consistent with, their prior knowledge in 25% or 75% of presented exemplars. In Experiment 3, children (N = 290) saw fictitious animal, artifact, or unfamiliar social categories that were either consistent or inconsistent with their prior knowledge in 20%, 40%, 60%, or 80% of exemplars. In the test, children made judgments about the likely co-occurence of features. In all experiments, prior knowledge and exemplar observation independently influenced children's categorization judgments. Utilization of prior knowledge was consistent across age and domain, but 10-year-olds were more sensitive to observed feature covariation. Training with larger categories increased the impact of observed feature covariation and decreased reliance on prior knowledge.

Developmental instability and right shift theory hypotheses concerning correlates of familial sinistrality: negative findings.

Both the right shift (Annett, 1985) and developmental instability (Yeo & Gangestad, 1993) theories of handedness predict that familial sinistrality (FS) should relate to hand skill asymmetries (HSA) on peg-moving tasks. Annett also hypothesises that both HSA and a procedure she derived for classifying individuals according to the pattern of their hand preferences for different manual activities can index the genotypes posited in her theory, i.e. she believes these variables are highly correlated. These hypotheses were tested in a sample of 280 dextral college students. Results failed to support the finding of Gangestad and Yeo (1994) that subjects showing greater hand skill asymmetry deviations from typical asymmetry had a greater probability of having a left-handed parent. There was also no support for Annett's finding that greater dextrality, as defined by her hand preference classification system, was negatively associated with familial sinistrality. Additionally, the relationship between HSA and Annett's hand preference classes was found to be exceedingly weak, contrary to Annett's theorising. These and other failures to find highly replicable differences between FS- and FS+ dextrals cast doubt on the validity of genetic or partial-genetic theories of handedness that posit a ''penetrance'' of a recessive non-dextrality-favouring gene that causes presumed dextral heterozygotic persons to differ from presumed homozygotic dominant persons in cognitive or manual skills.

Objective behavior associated with an "ordinary" mild headache: a surprising failure of pain onset to signal self-protective or self-regulatory behavior.

OBJECTIVE: The goal of this study was to determine whether onset of an "ordinary" headache initiated self-protective behavior or self-regulation, as indexed by a reduction in effort expenditure. METHODS: A nonclinical sample was employed. The ambition and performance accuracy of a headache-developing group (n = 23) and a sex-matched, headache-free group (n = 23) was compared during a series of mental arithmetic problems. Embedded within the series of math problems was a task involving recall of a stressor previously found to induce headache in many subjects. RESULTS: Onset of mild head pain did not lead to effort conservation; instead, heightened ambition appeared to characterize the headache-developing participants before as well as after headache onset. Headache-developing subjects also displayed a performance accuracy deficit. CONCLUSIONS: The data suggest unusually ambitious, effortful task engagement may contribute to the onset of mild "ordinary" headache. This possibility requires further examination under other controlled conditions as well as in the natural environment.

Neurologic validity of the Wisconsin Card Sorting Test with a pediatric population.

This study investigated the neurologic validity of the Wisconsin Card Sorting Test (WCST) with a pediatric population; that is, the ability of the test to detect dysfunction in the frontal lobes. Fifty children with diverse etiologies of brain dysfunction were classified via EEG, MRI, or CT as having left hemisphere, right hemisphere, or bilateral frontal, extrafrontal, or multifocal/diffuse regions of brain dysfunction. Findings failed to support the hypotheses that WCST performance is more impaired in frontal lesions than extrafrontal or multifocal/diffuse lesions, or that WCST performance is more impaired in left hemisphere lesions than right. Although the WCST is not helpful in localizing cerebral area of dysfunction, it may still be a clinically useful test for examining processes that children use to solve complex problems.

Socioeconomic influences on the transmission of human immunodeficiency virus infection: the hidden risk.

Worldwide, and in pockets of poverty in the United States, there is growing evidence that poverty is a major contributor to the spread of human immunodeficiency virus infection. Specific socioeconomic forces contributing to the spread of the infection include the status of women, prostitution, drug use in poor populations, the role of prisons, economic factors that disrupt families, and cultural attitudes. A lack of awareness of or an unwillingness to address the social, cultural, and economic forces contributing to the transmission of the human immunodeficiency virus have hampered attempts to stem the epidemic. A "social prevention" strategy is called for in which socioeconomic influences on human immunodeficiency virus transmission can be ameliorated. Practicing physicians should be aware of these forces because they profoundly influence the effectiveness of patient education, prevention, and treatment.