The burden of mental disorders and access to mental health and psychosocial support services in Syria and among Syrian refugees in neighboring countries: a systematic review.

BACKGROUND: Exposure to conflict, violence and forced displacement can increase poor mental health among affected populations. Our aim was to examine evidence on the burden of mental disorders and access to and effectiveness of mental health and psychosocial support (MHPSS) services in Syria and among Syrian refugees in neighboring countries. METHODS: A systematic review was done following systematic review criteria. Twelve bibliographic databases and additional gray literature sources were searched for quantitative and qualitative studies. Descriptive analysis and quality assessment were conducted. RESULTS: Twenty-eight eligible studies were identified, of which two were with conflict-affected populations within Syria. Levels of post-traumatic stress disorder ranged from 16 to 84%, depression from 11 to 49%, and anxiety disorder from 49 to 55%. Common risk factors were exposures to trauma and having a personal or family history of mental disorder. Financial and socio-cultural barriers were identified as the main obstacles to accessing MHPSS care. Evaluations of MHPSS services, albeit from predominantly nonrandomised designs, reported positive treatment outcomes. CONCLUSIONS: The MHPSS burden was high, but with considerable variation between studies. There are key evidence gaps on: MHPSS burden and interventions-particularly for those living within Syria; access and barriers to care; and implementation and evaluation of MHPSS interventions.

Population physiologically based modeling of pirlimycin milk concentrations in dairy cows.

Predictions of drug residues in milk are critical in food protection and are a major consideration in the economics of treatment of mastitis in dairy cows. Nonlinear mixed-effects modeling (NLME) has been advocated as a suitable pharmaco-statistical method for the study of drug residues in milk. Recent developments in physiologically based pharmacokinetic (PBPK) modeling of intramammary drugs allow the combination of a mechanistic description of milk pharmacokinetics with NLME methods. The PBPK model was applied to NLME analysis of a data set consisting of milk drug concentrations from 78 healthy cows and 117 with clinical mastitis. Pirlimycin milk pharmacokinetics were adequately described by the model across the range of observed concentrations. Mastitis was characterized by increased variance in milk production volume. Udder residual volume was larger in cows with 1, or 2 or greater diseased mammary glands than in the healthy cows. Low-producing cows had a greater risk of prolonged milk residues. With the exclusion of the low-production cows, the model predicted that healthy cows required a milk discard time 12 h longer than that indicated by the label, and the diseased cows 36 h longer than indicated by the label. More pirlimycin was systemically absorbed in the gram-positive infected compared with the gram-negative infected or healthy cows, suggesting a greater risk of violative meat residues in gram-positive infected cows. Using NLME and PBPK models, we identified factors associated with changes in pirlimycin milk residues that may affect food safety. This model extends the verification of a simple physiologically based framework for the study of intramammary drugs.

Controlled before-after intervention study of suburb-wide street changes to increase walking and cycling: Te Ara Mua-Future Streets study design.

BACKGROUND: Achieving a shift from car use to walking, cycling and public transport in cities is a crucial part of healthier, more environmentally sustainable human habitats. Creating supportive active travel environments is an important precursor to this shift. The longevity of urban infrastructure necessitates retrofitting existing suburban neighbourhoods. Previous studies of the effects of street changes have generally relied on natural experiments, have included few outcomes, and have seldom attempted to understand the equity impacts of such interventions. METHODS: In this paper we describe the design of Te Ara Mua - Future Streets, a mixed-methods, controlled before-after intervention study to assess the effect of retrofitting street changes at the suburb scale on multiple health, social and environmental outcomes. The study has a particular focus on identifying factors that improve walking and cycling to local destinations in low-income neighbourhoods and on reducing social and health inequities experienced by Maori (Indigenous New Zealanders) and Pacific people. Qualitative system dynamics modelling was used to develop a causal theory for the relationships between active travel, and walking and cycling infrastructure. On this basis we selected outcomes of interest. Together with the transport funder, we triangulated best evidence from the literature, transport policy makers, urban design professionals and community knowledge to develop interventions that were contextually and culturally appropriate. Using a combination of direct observation and random sample face to face surveys, we are measuring outcomes in these domains of wellbeing: road-user behaviour, changes to travel mode for short trips, physical activity, air quality, road traffic injuries, greenhouse gas emissions, and perceptions of neighbourhood social connection, safety, and walking and cycling infrastructure . DISCUSSION: While building on previous natural experiments, Te Ara Mua - Future Streets is unique in testing an intervention designed by the research team, community and transport investors together; including a wide range of objective outcome measures; and having an equity focus. When undertaking integrated intervention studies of this kind, a careful balance is needed between epidemiological imperatives, the constraints of transport funding and implementation and community priorities, while retaining the ability to contribute new evidence for healthy, equitable transport policy. The study was retrospectively registered as a clinical trial on 21 June 2018 in the ISCRTN registry: ISRCTN89845334 http://www.isrctn.com/ISRCTN89845334.

Ultrafast spectroscopy, superluminescence and theoretical modeling of a two-photon absorbing fluorene derivative.

A comprehensive study of photophysical and photochemical properties of an unsymmetrical fluorene derivative is presented, including linear absorption, fluorescence excitation anisotropy, photochemical stability, steady-state fluorescence, and fluorescence lifetimes in organic solvents of different polarities. Nonlinear optical properties were investigated using Z-scan measurements of degenerate two-photon absorption and femtosecond pump-probe spectroscopy. The strongly fluorescent compound exhibited good photostability, positioning it for use in a number of applications. A dramatic increase in fluorescence intensity along with spectral narrowing was observed under femtosecond pumping, demonstrating amplified spontaneous emission. An extensive set of experimental data is rationalized based on essential state models.

The cardiopulmonary effects and quality of anesthesia after induction with alfaxalone in 2-hydroxypropyl-ß-cyclodextrin in dogs and cats: a systematic review.

To systematically review the quality of evidence comparing the cardiopulmonary effects and quality of anesthesia after induction with alfaxalone vs. other anesthetic agents in dogs and cats. Studies published from 2001 until 20th May 2013 were identified with the terms 'alfaxan' OR 'alfaxalone' OR 'alphaxalone' in electronic databases: Discovery, PubMed, ScienceDirect, and Wiley Interscience. The study design and risk of bias of all included studies were assessed. Twenty-two studies from 408 (22 of 408, 5.39%) satisfied the inclusion criteria. Fourteen studies (14 of 22, 64%) focused on dogs and nine (9 of 22, 40%) on cats. One study had both dogs and cats as subjects. (Hunt et al., 2013) Twelve studies were rated an LOE1, and six of these as ROB1. One, seven, and two studies were rated as LOE2, LOE3, and LOE5, respectively. In dogs, strong evidence shows that induction quality with either alfaxalone-HPCD or propofol is smooth. Moderate evidence supports this finding in cats. In dogs, moderate evidence shows that there is no significant change in heart rate after induction with either alfaxalone-HPCD or propofol. In cats, moderate evidence shows no significant difference in postinduction respiratory rate and heart rate between alfaxalone-HPCD and propofol induction. Strong evidence shows dogs and cats have smooth recoveries after induction using either alfaxalone-HPCD or propofol, before reaching sternal recumbency.

Pharmacokinetics of enrofloxacin following oral and subcutaneous administration in the common ringtail possum (Pseudocheirus peregrinus).

[Correction added on 23 March 2015, after first online publication: Terminal half-life values of enrofloxacin is corrected in the fourth sentence of the abstract] Clinically healthy common ringtail possums (n = 5) received single doses of 10 mg/kg enrofloxacin orally and then 2 weeks later subcutaneously. Serial plasma samples were collected over 24 h for each treatment phase, and enrofloxacin concentrations were determined using a validated HPLC assay. Pharmacokinetic parameters were determined by noncompartmental analysis. Following oral administration, plasma concentrations were of therapeutic relevance (Cmax median 5.45 µg/mL, range 2.98-6.9 µg/mL), with terminal-phase half-life (t½ ) shorter than in other species (median 3.09 h, range 1.79-5.30 h). In contrast, subcutaneous administration of enrofloxacin did not achieve effective plasma concentrations, with plasma concentrations too erratic to fit the noncompartmental model except in one animal. On the basis of the AUC:MIC, enrofloxacin administered at 10 mg/kg orally, but not subcutaneously, is likely to be effective against a range of bacterial species that have been reported in common ringtail possums.

Binding of transmembrane mucins to galectin-3 limits herpesvirus 1 infection of human corneal keratinocytes.

Epithelial cells lining mucosal surfaces impose multiple barriers to viral infection. At the ocular surface, the carbohydrate-binding protein galectin-3 maintains barrier function by cross-linking transmembrane mucins on the apical glycocalyx. Despite these defense mechanisms, many viruses have evolved to exploit fundamental cellular processes on host cells. Here, we use affinity assays to show that herpes simplex virus type 1 (HSV-1), but not HSV-2, binds human galectin-3. Knockdown of galectin-3 in human corneal keratinocytes by small interfering RNA significantly impaired HSV-1 infection, but not expression of nectin-1, indicating that galectin-3 is a herpesvirus entry mediator. Interestingly, exposure of epithelial cell cultures to transmembrane mucin isolates decreased viral infectivity. Moreover, HSV-1 failed to elute the biological counterreceptor MUC16 from galectin-3 affinity columns, suggesting that association of transmembrane mucins to galectin-3 provides protection against viral infection. Together, these results indicate that HSV-1 exploits galectin-3 to enhance virus attachment to host cells and support a protective role for transmembrane mucins under physiological conditions by masking viral entry mediators on the epithelial glycocalyx.

Neural correlates involved in perspective-taking in early childhood.

Learning to consider another person's perspective is pivotal in early social development. Still, little is known about the neural underpinnings involved in perspective-taking in early childhood. In this EEG study, we examined 4-year-old children's brain activity during a live, social interaction that involved perspective-taking. Children were asked to pass one of two toys to another person. To decide which toy to pass, they had to consider either their partner's perspective (perspective-taking) or visual features unrelated to their partner's perspective (control). We analyzed power changes in midfrontal and temporal-parietal EEG channels. The results indicated that children showed higher power around 7 Hz at right temporal-parietal channels for perspective-taking compared to control trials. This power difference was positively correlated with children's perspective-taking performance, specifically for trials in which they needed to pass the toy their partner could not see. A similar power difference at right temporal-parietal channels was seen when comparing perspective-taking trials where children's visual access mismatched rather than matched that of their partner. No differences were detected for midfrontal channels. In sum, we identified distinct neural activity as 4-year-olds considered another person's perspective in a live interaction; this activity converges with neural findings of adults' social processing network.

Interfacial interaction between transmembrane ocular mucins and adhesive polymers and dendrimers analyzed by surface plasmon resonance.

PURPOSE: Development of the first in vitro method based on biosensor chip technology designed for probing the interfacial interaction phenomena between transmembrane ocular mucins and adhesive polymers and dendrimers intended for ophthalmic administration. METHODS: The surface plasmon resonance (SPR) technique was used. A transmembrane ocular mucin surface was prepared on the chip surface and characterized by QCM-D (Quartz Crystal Microbalance with Dissipation) and XPS (X-ray photoelectron spectroscopy). The mucoadhesive molecules tested were: hyaluronic acid (HA), carboxymethyl cellulose (CMC), hydroxypropylmethyl cellulose (HPMC), chitosan (Ch) and polyamidoamine dendrimers (PAMAM). RESULTS: While Ch originated interfacial interaction with ocular transmembrane mucins, for HA, CMC and HPMC, chain interdiffusion seemed to be mandatory for bioadherence at the concentrations used in ophthalmic clinical practise. Interestingly, PAMAM dendrimers developed permanent interfacial interactions with transmembrane ocular mucins whatever their surface chemical groups, showing a relevant importance of co-operative effect of these multivalent systems. Polymers developed interfacial interactions with ocular membrane-associated mucins in the following order: Ch(1 %) > G4PAMAM-NH(2)(2 %) = G4PAMAM-OH(2 %) > G3.5PAMAM-COOH(2 %)>> CMC(0.5 %) = HA(0.2 %) = HPMC(0.3 %). CONCLUSIONS: The method proposed is useful to discern between the mucin-polymer chemical interactions at molecular scale. Results reinforce the usefulness of chitosan and dendrimers as polymers able to increase the retention time of drugs on the ocular surface and hence their bioavailability.

Water consumption and wastage behaviour in pigs: implications for antimicrobial administration and stewardship.

Daily water use and wastage patterns of pigs have major effects on the efficacy of in-water antimicrobial dosing events when conducted for metaphylaxis or to treat clinical disease. However, daily water use and wastage patterns of pigs are not routinely quantified on farms and are not well understood. We conducted a prospective, observational 27-day study of the daily water use and wastage patterns of a pen group of 15 finisher pigs reared in a farm building. We found that the group of pigs wasted a median of 36.5% of the water used per day. We developed models of the patterns of water used and wasted by pigs over each 24-h period using a Bayesian statistical method with the brm() function in the brms package. Both patterns were uni-modal, peaking at 1400-1700, and closely aligned. Wastage was slightly greater during hours of higher water use. We have shown that it is feasible to quantify the water use and wastage patterns of pigs in farm buildings using a system that records and aggregates data, and analyses them using hierarchical generalised additive models. This system could support more efficacious in-water antimicrobial dosing on farms, and better antimicrobial stewardship, by helping to reduce the quantities of antimicrobials used and disseminated into the environment.

Tumoricidal activity of tumor necrosis factor-related apoptosis-inducing ligand in vivo.

To evaluate the utility of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) as a cancer therapeutic, we created leucine zipper (LZ) forms of human (hu) and murine (mu) TRAIL to promote and stabilize the formation of trimers. Both were biologically active, inducing apoptosis of both human and murine target cells in vitro with similar specific activities. In contrast to the fulminant hepatotoxicity of LZ-huCD95L in vivo, administration of either LZ-huTRAIL or LZ-muTRAIL did not seem toxic to normal tissues of mice. Finally, repeated treatments with LZ-huTRAIL actively suppressed growth of the TRAIL-sensitive human mammary adenocarcinoma cell line MDA-231 in CB.17 (SCID) mice, and histologic examination of tumors from SCID mice treated with LZ-huTRAIL demonstrated clear areas of apoptotic necrosis within 9-12 hours of injection.

Risk of brain tumours in relation to estimated RF dose from mobile phones: results from five Interphone countries.

OBJECTIVES: The objective of this study was to examine the associations of brain tumours with radio frequency (RF) fields from mobile phones. METHODS: Patients with brain tumour from the Australian, Canadian, French, Israeli and New Zealand components of the Interphone Study, whose tumours were localised by neuroradiologists, were analysed. Controls were matched on age, sex and region and allocated the 'tumour location' of their matched case. Analyses included 553 glioma and 676 meningioma cases and 1762 and 1911 controls, respectively. RF dose was estimated as total cumulative specific energy (TCSE; J/kg) absorbed at the tumour's estimated centre taking into account multiple RF exposure determinants. RESULTS: ORs with ever having been a regular mobile phone user were 0.93 (95% CI 0.73 to 1.18) for glioma and 0.80 (95% CI 0.66 to 0.96) for meningioma. ORs for glioma were below 1 in the first four quintiles of TCSE but above 1 in the highest quintile, 1.35 (95% CI 0.96 to 1.90). The OR increased with increasing TCSE 7+ years before diagnosis (p-trend 0.01; OR 1.91, 95% CI 1.05 to 3.47 in the highest quintile). A complementary analysis in which 44 glioma and 135 meningioma cases in the most exposed area of the brain were compared with gliomas and meningiomas located elsewhere in the brain showed increased ORs for tumours in the most exposed part of the brain in those with 10+ years of mobile phone use (OR 2.80, 95% CI 1.13 to 6.94 for glioma). Patterns for meningioma were similar, but ORs were lower, many below 1.0. CONCLUSIONS: There were suggestions of an increased risk of glioma in long-term mobile phone users with high RF exposure and of similar, but apparently much smaller, increases in meningioma risk. The uncertainty of these results requires that they be replicated before a causal interpretation can be made.

Observations on the use of a pain numbing device for repetitive percutaneous sampling in sheep.

AIMS: To evaluate the success of a commercially available analgesic device (CoolSense; Coolsense Ltd, Tel Aviv, Israel) in ameliorating pain while sampling from subcutaneous tissue cages in sheep. METHODS: The CoolSense device was used as part of a major parent study involving repetitive percutaneous sampling of subcutaneous tissue cages in seven sheep. Sampling was performed by passing a hypodermic needle through the skin and withdrawing fluid from the tissue cage. Each sheep had 10 tissue cages that were individually sampled 14 times over 74 h. The device was placed on the skin of the sampling site immediately before sampling cooling and numbing the skin. The reaction of the sheep was observed by the operators, flinching or jumping as the needle was passed through the skin was deemed to be a failure. We recorded the success or failure of the device for each needle stick. This was opportunistic data collection as part of a pharmacokinetic trial, therefore no controls were included. RESULTS: A total of 1655 observations were recorded and then analysed using a generalised linear mixed model. Overall, 1380 of 1655 (83.4%) observations were recorded as successfully providing analgesia. Marked inter-occasion variability was noted with success ranging from 61.42% to 92.86% across sheep:period (approximately 140 observations each). As no controls were available, the effect of treatment could not be evaluated. CONCLUSIONS AND CLINICAL RELEVANCE: The CoolSense device is a viable option for veterinary research and clinical applications.

Assessment of the clinical usefulness of ultrasound-guided cytological specimens obtained from gastrointestinal lesions in dogs and cats.

OBJECTIVES: Cytological biopsies are an integral additional test to an abdominal ultrasound when a lesion is identified, but there is little published on factors that that may impact achieving a clinically useful sample of gastrointestinal lesions obtained by ultrasound-guided fine-needle cytologic biopsy. This retrospective, descriptive study aimed to assess factors that may influence the clinical usefulness of submitted cytological samples collected from gastrointestinal lesions by ultrasound-guided percutaneous fine-needle cytologic biopsy. MATERIAL AND METHODS: Gastrointestinal cytological samples obtained from 25 dogs and 19 cats over 2.5 years were reviewed and determined as clinically useful or clinically useless as per the cytology report. Variables dependent on the ultrasound exam that were used in the analysis included lesion location, lesion thickness, loss of gastrointestinal layering, and the number of slides submitted. RESULTS: Thirty (30/44) of the submitted cytological samples were considered clinically useful. Factors associated with achieving a clinically useful sample in univariable models included the number of slides submitted and the thickness of the lesion. However, these two variables appear inter-related, as a weak correlation existed between them. Where histologic biopsies were obtained, a clinically useful sample had a partial or complete agreement with histology in three of 12 and eight of 12 cases, respectively. CLINICAL SIGNIFICANCE: Ultrasound-guided fine-needle cytological biopsies of gastrointestinal masses provided a clinically useful sample in two-third of the cases, especially if more slides were provided to the cytologist and thicker lesions were sampled.

Nurse-led clinics for strict hypertension control are effective long term: a 7 year follow-up study.

AIMS: The primary aim was to assess long-term blood pressure in 110 patients with Type 2 diabetes who had achieved optimal blood pressure control during attendance at a protocol-based nurse-led hypertension intensive intervention clinic 7 years previously. The secondary aim was to assess modifiable cardiovascular risk factor status. METHODS: One hundred and ten patients who attended the clinic during 2000-2002 were selected to reattend to have their blood pressure measured to the same standard as it was during the intensive intervention clinic, by the same specialist nurse. Treatment details were recorded. RESULTS: Of the 110 patients, 36 (33%) had died; 69 (63%) of the remaining 74 patients were eligible to be contacted by letter; and 35 (51%) agreed to reattend. Age was 70 +/- 9 years; 21 (60%) were male; and the duration of diabetes was 17 +/- 7 years. Compared with 7 years previously, there was no difference in blood pressure control (systolic 130 +/- 17 vs. 131 +/- 16 mmHg, P = 0.62; diastolic 68 +/- 9 vs. 65 +/- 9 mmHg, P = 0.11). The number of patients with blood pressure <130/80 mmHg remained the same: 17 (49%) vs. 17 (49%; P > 0.99). During the 7 year period, 14 (40%) vs. 20 (57%) had macrovascular disease (P = 0.23), and 14 (40%) vs. 19 (54%) microvascular disease (P = 0.33). Thirteen (37%) vs. 18 (51%) were taking three or more antihypertensive drugs (P = 0.33), and 26 (74%) vs. 28 (80%) angiotensin-converting enzyme inhibitor or angiotensin receptor blocker (P = 0.77). CONCLUSIONS: Optimal blood pressure control was sustained with no significant changes to antihypertensive medication, demonstrating the effectiveness of a protocol-based nurse-led clinic in achieving strict BP control.

Anatomical differentiation of direct and indirect inguinal hernias: Is it worthwhile in the modern era?

The study aimed to assess the clinical accuracy of differentiating direct and indirect inguinal hernias preoperatively by different grades of surgeons. A retrospective audit was conducted over a 9-year period and comprised all adult inguinal hernia patients operated by one consultant surgeon. The hernias were differentiated into direct and indirect hernias based on the direction of cough impulse and the deep ring occlusion test. The preoperative diagnosis was compared with intraoperative findings. During the study period, 503 patients were examined. Of these, 272 patients were diagnosed as having indirect hernias and 56 patients as having direct hernias. In 175 patients, no attempt was made to differentiate indirect and direct hernias. When compared with intraoperative findings, the diagnosis was correct in 77% of the indirect hernias and 55% of direct hernias. Of the patients in whom no differentiation was attempted, 115 patients had indirect hernias, 56 had direct hernias, and four had both. For indirect hernias, the diagnostic accuracy was 82, 63, and 30% for consultant, registrars, and senior house officers. For direct hernias, the diagnostic accuracy was 66, 50, and 44%, respectively. This study demonstrates relatively poor accuracy in diagnosing direct inguinal hernias regardless of seniority.

Survival time and relapse in dogs with meningoencephalomyelitis of unknown origin treated with prednisolone and ciclosporin: a retrospective study.

OBJECTIVE: To analyse outcome in dogs with a presumptive diagnosis of meningoencephalomyelitis of unknown origin (MUO) treated with prednisolone and ciclosporin and to assess the effect of a number of patient variables on survival time and rate of relapse. DESIGN: Retrospective case series. METHODS: Medical records of 40 client-owned dogs with a diagnosis of MUO treated with prednisolone and ciclosporin at one institution between June 2010 and January 2018 were reviewed retrospectively to assess survival times and prognostic indicators for death and/or relapse. The minimum follow-up time was 11 months post-diagnosis. RESULTS: Median survival was 1345 days (95% confidence interval: 487-∞). No associations with hazard of death or relapse were detected for the presence of multifocal magnetic resonance imaging (MRI) abnormalities, caudal fossa location of MRI abnormalities, value of cerebrospinal fluid total nucleated cell count or total protein at time of diagnosis, or suspected elevation in intracranial pressure at time of diagnosis. CONCLUSION: Protracted survival time may be achieved with a treatment combination of prednisolone and ciclosporin. Suspected elevation in intracranial pressure at the time of diagnosis did not affect long-term outcome in this cohort.

Breed is associated with the ABCB1-1Δ mutation in Australian dogs.

OBJECTIVE: The ABCB1 gene encodes P-glycoprotein (P-gp), a cellular membrane pump. One functional mutation that leads to expression of a less functional form of P-gp, ABCB1-1Δ, has been described in dogs. Individuals with this mutation can have severe adverse reactions to common veterinary pharmaceuticals that are known substrates of this pump. We investigated the detection of this mutation in samples submitted to two Australian diagnostic laboratories. METHODS: A total of 4842 dogs across 27 breeds were tested for the ABCB1-1Δ mutation from buccal swabs or EDTA blood using standard PCR, multiplex PCR, or genotyping chip. Statistical analysis was applied to determine the proportions and odds ratios of the ABCB1-1Δ mutation in herding breeds compared with non-herding breeds. RESULTS: The ABCB1-1Δ mutation was detected in nine breeds. The most commonly affected breeds were collies, Australian shepherds, white Swiss shepherds, and Shetland sheepdogs. Of 32 dogs in 18 non-herding breeds tested, one cocker spaniel and one labradoodle were positive for the mutation, both heterozygous. CONCLUSION: The most frequently affected breeds for ABCB1-1Δ mutation are the collie, Australian shepherd, white Swiss shepherd and Shetland sheepdog. As the mutation is associated with an increased incidence of adverse reactions to commonly used pharmaceuticals, veterinarians need to be aware of the breeds at most risk of carrying this mutation and consider testing these individuals prior to administering these medications.

Cardiac arrhythmia and nocturnal hypoglycaemia in type 1 diabetes--the 'dead in bed' syndrome revisited.

AIMS/HYPOTHESIS: Sudden nocturnal death in type 1 diabetes ('dead in bed' syndrome) is thought to be due to ECG QT prolongation with subsequent ventricular tachyarrhythmia in response to nocturnal hypoglycaemia. We investigated this theoretical mechanism using continuous ECG and continuous glucose monitoring in a group of patients with type 1 diabetes. METHODS: Twenty-five patients with type 1 diabetes (age 20-50 years) underwent two separate 24 h ECG and continuous glucose monitoring periods. Patients were fully ambulant and carried out normal daily activities. RESULTS: There were 13 episodes (26% of recordings) of nocturnal hypoglycaemia, eight of <2.2 mmol/l and five of 2.2-3.4 mmol/l. Corrected QT interval (QTc) was longer during nocturnal hypoglycaemia compared with normoglycaemic control periods (445 +/- 40 vs 415 +/- 23 ms; p = 0.037). Cardiac rate and rhythm disturbances (excluding sinus tachycardia) were seen in eight of the 13 nocturnal hypoglycaemia episodes (62%). These were sinus bradycardia (<40 beats/min; three episodes), ventricular ectopics (three episodes), atrial ectopics (one) and P wave abnormalities (one). CONCLUSIONS/INTERPRETATION: This study demonstrates QTc prolongation and cardiac rate/rhythm disturbances in response to episodes of nocturnal hypoglycaemia in ambulant patients with type 1 diabetes. This may support an arrhythmic basis for the 'dead in bed' syndrome.

Determinants of mobile phone output power in a multinational study: implications for exposure assessment.

OBJECTIVES: The output power of a mobile phone is directly related to its radiofrequency (RF) electromagnetic field strength, and may theoretically vary substantially in different networks and phone use circumstances due to power control technologies. To improve indices of RF exposure for epidemiological studies, we assessed determinants of mobile phone output power in a multinational study. METHODS: More than 500 volunteers in 12 countries used Global System for Mobile communications software-modified phones (GSM SMPs) for approximately 1 month each. The SMPs recorded date, time, and duration of each call, and the frequency band and output power at fixed sampling intervals throughout each call. Questionnaires provided information on the typical circumstances of an individual's phone use. Linear regression models were used to analyse the influence of possible explanatory variables on the average output power and the percentage call time at maximum power for each call. RESULTS: Measurements of over 60,000 phone calls showed that the average output power was approximately 50% of the maximum, and that output power varied by a factor of up to 2 to 3 between study centres and network operators. Maximum power was used during a considerable proportion of call time (39% on average). Output power decreased with increasing call duration, but showed little variation in relation to reported frequency of use while in a moving vehicle or inside buildings. Higher output powers for rural compared with urban use of the SMP were observed principally in Sweden where the study covered very sparsely populated areas. CONCLUSIONS: Average power levels are substantially higher than the minimum levels theoretically achievable in GSM networks. Exposure indices could be improved by accounting for average power levels of different telecommunications systems. There appears to be little value in gathering information on circumstances of phone use other than use in very sparsely populated regions.