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Background It is widely accepted that the risk of hepatitis C virus (HCV) vertical transmission (VT) is 5%–6% in monoinfected women, and that 25%–40% of HCV infection clears spontaneously within 5 years. However, there is no consensus on how VT rates should be estimated, and there is a lack of information on VT rates “net” of clearance. Methods We reanalyzed data on 1749 children in 3 prospective cohorts to obtain coherent estimates of overall VT rate and VT rates net of clearance at different ages. Clearance rates were used to impute the proportion of uninfected children who had been infected and then cleared before testing negative. The proportion of transmission early in utero, late in utero, and at delivery was estimated from data on the proportion of HCV RNA positive within 3 days of birth, and differences between elective cesarean and nonelective cesarean deliveries. Results Overall VT rates were 7.2% (95% credible interval [CrI], 5.6%–8.9%) in mothers who were human immunodeficiency virus (HIV) negative and 12.1% (95% CrI, 8.6%–16.8%) in HIV-coinfected women. The corresponding rates net of clearance at 5 years were 2.4% (95% CrI, 1.1%–4.1%), and 4.1% (95% CrI, 1.7%–7.3%). We estimated that 24.8% (95% CrI, 12.1%–40.8%) of infections occur early in utero, 66.0% (95% CrI, 42.5%–83.3%) later in utero, and 9.3% (95% CrI, 0.5%–30.6%) during delivery. Conclusions Overall VT rates are about 24% higher than previously assumed, but the risk of infection persisting beyond age 5 years is about 38% lower. The results can inform design of trials of interventions to prevent or treat pediatric HCV infection, and strategies to manage children exposed in utero.

ObjectivesTo identify aspects of the organisation and delivery of acute inpatient services for people with dementia that are associated with shorter length of hospital stay.Design and settingRetrospective cohort study of patients admitted to 200 general hospitals in England and Wales.Participants10 106 people with dementia who took part in the third round of National Audit of Dementia.Main outcome measureLength of admission to hospital.ResultsThe median length of stay was 12 days (IQR=6–23 days). People with dementia spent less time in hospital when discharge planning was initiated within 24 hours of admission (estimated effect −0.24, 95% CI: −0.29 to −0.18, pConclusionsThe way that services for inpatients with dementia are delivered can influence how long they spend in hospital. Initiating discharge planning within the first 24 hours of admission may help reduce the amount of time that people with dementia spend in hospital.

BackgroundCurrent guidelines recommend that infants born to women with hepatitis C (HCV) viremia are screened for HCV antibody at age 18 months, and if positive, referred for RNA testing at 3 years to confirm chronic infection. This policy is based in part on analyses suggesting 25%-40% of vertically acquired HCV infections clear spontaneously within 4-5 years.MethodsData on 179 infants with RNA and/or anti-HCV evidence of vertically acquired viraemia (single PCR+) or confirmed infection (2 PCR+ or anti-HCV beyond 18 months) in three prospective European cohorts were investigated. Ages at clearance of viremia and confirmed infection were estimated taking account of interval censoring and delayed entry. We also investigated clearance in infants in whom RNA was not detectable until after 6 weeks.ResultsClearance rates decline rapidly over the first 6 months. An estimated 90.6% (95%CrI: 83.5-95.9) of viremia cleared by 5 years, most within 3 months, and 65.9% (50.1-81.6) of confirmed infection cleared by 5 years, at a median 12.4 (7.1-18.9) months. If treatment began at age 6 months, 18 months or 3 years, at least 59.0% (42.0-76.9), 39.7 (17.9-65.9), and 20.9 (4.6-44.8) of those treated would clear without treatment. In seven (6.6%) confirmed infections, RNA was not detectable until after 6 weeks, and in 2 (1.9%) not until after 6 months. However, all such cases subsequently cleared.ConclusionsMost viraemia clears within 3 months, and most confirmed infection by 3 years. Delaying treatment avoids but does not eliminate over-treatment and should be balanced against loss to follow-up.Key pointsBased on a re-analysis of the largest purely prospective dataset assembled so far, 66% (50-82) of confirmed vertically acquired HCV clears spontaneously by age 5 years, rather than the 25-40% assumed in guidelines.

BackgroundIt is widely accepted that the risk of HCV vertical transmission (VT) is 5-6% in mono-infected women, and that 25-40% of HCV infection clears spontaneously within 5 years. However, VT and clearance rates have not been estimated from the same datasets, and there is a lack of information on VT rates “net” of clearance.MethodsWe re-analysed data on 1749 children in 3 prospective cohorts to obtain coherent estimates of overall VT rate and VT rates “net” of clearance at different ages. Clearance rates were used to impute the proportion of uninfected children who had been infected and then cleared before testing negative. The proportion of transmission early in utero, late in utero and at delivery was estimated from data on the proportion of RNA positives in samples tested within three days of birth, and differences between elective caesarean and non-elective caesarean deliveries.FindingsOverall VT rates were 7.2% (95% credible interval 5.6-8.9) in mothers who were HIV negative and 12.1% (8.6-16.8) in HIV-co-infected women. The corresponding rates net of clearance at 5 years were 2.4% (1.1-4.1) and 4.1% (1.7-7.3). We estimated that 24.8% (12.1-40.8) of infections occur early in utero, 66.0% (42.5-83.3) later in utero, and 9.3% (0.5-30.6) during delivery.ConclusionOverall VT rates are about 24% higher than previously assumed, but the risk of infection persisting beyond age 5 years is about 38% lower. The results can inform design of trials of to prevent or treat pediatric HCV infection, and strategies to manage children exposed in utero.Key pointsTaking account of infections that would have cleared spontaneously before detection, the rate of HCV vertical transmission is 7.2% (95%CrI 5.6-8.9) in mono-infected women, but transmission “net” of clearance is 3.1% (1.8-4.4) at 3 years, and 2.4% (1.1-4.1) at 5.

Background In-center hemodialysis (HD) has been the standard treatment for older dialysis patients, but reports suggest an associated decline in physical and cognitive function. Cross-sectional data suggest that assisted peritoneal dialysis (aPD), an alternative treatment, is associated with quality of life (QoL) outcomes that are comparable to in-center HD. We compared longitudinal changes in QoL between modalities. Methods We enrolled 106 aPD patients, matched with 100 HD patients from 20 renal centers in England and Northern Ireland. Patients were assessed quarterly for 2 years using the Hospital Anxiety and Depression Scale (HADS), SF-12 physical and mental scores, symptom score, Illness Intrusiveness Rating Scale (IIRS), Barthel's score, and the Renal Treatment Satisfaction Questionnaire (RTSQ). Mixed model analysis was used to assess the impact of dialysis modality on these outcomes during follow-up. P values were adjusted for multiple significance testing. Results Multivariate analysis showed no difference in any of the outcome measures between aPD and HD. Longitudinal trends in outcomes were also not significantly different. Higher age at baseline was associated with lower IIRS and RTSQ scores during follow-up. One-hundred and twenty-five (60.6%) patients dropped out of the study: 59 (28.6%) died, 61 (29.6%) withdrew during follow-up, and 5 (2.5%) were transplanted. Conclusions Quality of life outcomes in frail older aPD patients were equivalent to those receiving in-center HD. Assisted PD is thus a valid alternative to HD for older people with end-stage kidney disease (ESKD) wishing to dialyze at home.

To evaluate the relationship between adipose tissue measurements and anterior bowing of the posterior tracheal wall in a large nonselected group of patients undergoing CT pulmonary angiography (CTPA). Consecutive patients undergoing CTPA over a 4-month period were analyzed retrospectively. Using an adapted scoring system (posterior bowing, flattening, mild/moderate or severe anterior bowing of the posterior tracheal membrane), the axial morphology and cross-sectional area of the trachea at the narrowest point and 1 cm above the aortic arch were evaluated. Measurements of adipose tissue were taken (anterior mediastinal fat width, sagittal upper abdominal diameter and subcutaneous fat thickness at the level of the costophrenic angle). Relationships between tracheal morphology and measurements of adipose tissue were analyzed. 296 patients were included (120 males, 176 females, mean age 59 years, range 19–90). Severe anterior bowing of the posterior tracheal wall correlated with increasing sagittal upper abdominal diameter (p = 0.002). Mild/moderate and severe anterior bowing of the posterior tracheal wall correlated with increasing mediastinal fat width (p = 0.000 and p = 0.031, respectively). Tracheal cross-sectional area was inversely correlated with increasing subcutaneous fat thickness (p = 0.022). The findings demonstrate a statistically significant relationship between CT tracheal morphology and adipose tissue measurements in a large nonselected population. • There is increasing interest in the effects of obesity on the airways. • A relationship between anterior bowing of the posterior tracheal wall and adipose tissue measurements is demonstrated. • This is of clinical relevance in an increasingly obese population. • Further studies with functional correlation are required.

The carbonation rate of concrete has implications for the lifecycle carbon emissions of concrete. This paper describes the reported effect of several variables on the rate of concrete carbonation and collates a data set of measurements published in the literature. Many studies producing predictive models for the carbonation rate constant, K, use only small data sets. 1999 measurements of carbonation depth as a function of time and other variables were collected for analysis. Models in the form ln (K) = a + bI1 + cI2 + … have been produced by which the rate of carbonation can be predicted. Hierarchical Models were used to combine different authors' data and introduces a new explanatory variable called ‘origin’, which indicates whether the concrete was taken from a working structure or cast specifically for experiments. Two models of the carbonation rate using concrete properties have been produced, allowing prediction of K over a range of conditions and compositions.

Sepsis is the leading cause of direct maternal mortality, but there are no data directly comparing the response to sepsis in pregnant and nonpregnant (NP) individuals. This study uses a mouse model of sepsis to test the hypothesis that the cardiovascular response to sepsis is more marked during pregnancy. Female CD1 mice had radiotelemetry probes implanted and were time mated. NP and day 16 pregnant CD-1 mice received intraperitoneal lipopolysaccharide (LPS; 10 μg, serotype 0111: B4). In a separate study, tissue and serum (for RNA, protein and flow cytometry studies), aorta and uterine vessels (for wire myography) were collected after LPS or vehicle control administration. Administration of LPS resulted in a greater fall in blood pressure in pregnant mice compared to NP mice. This occurred with similar changes in the circulating levels of cytokines, vasoactive factors, and circulating leukocytes, but with a greater monocyte and lesser neutrophil margination in the lungs of pregnant mice. Baseline markers of cardiac dysfunction and apoptosis as well as cytokine expression were higher in pregnant mice, but the response to LPS was similar in both groups as was the ex vivo assessment of vascular function. In pregnant mice, nonfatal sepsis is associated with a more marked hypotensive response but not a greater immune response. We conclude that endotoxemia induces a more marked hypotensive response in pregnant compared to NP mice. These changes were not associated with a more marked systemic inflammatory response in pregnant mice, although monocyte lung margination was greater. The more marked hypotensive response to LPS may explain the greater vulnerability to some infections exhibited by pregnant women.

BACKGROUND AND OBJECTIVE: Supportive care remains the mainstay of therapy in bronchiolitis. Earlier studies suggest that helium-oxygen therapy may be beneficial, but evidence is limited. We aimed to compare efficacy of 2 treatment gases, Heliox and Airox (21% oxygen + 79% helium or nitrogen, respectively), on length of hospital treatment for bronchiolitis. METHODS: This was a multicenter randomized blinded controlled trial of 319 bronchiolitic infant subjects randomly assigned to either gas; 281 subjects completed the study (140 Heliox, 141 Airox), whose data was analyzed. Treatment was delivered via facemask (nasal cannula, if the facemask intolerant) ± continuous positive airway pressure (CPAP). Severe bronchiolitics received CPAP from the start. Primary end point was length of treatment (LoT) required to alleviate hypoxia and respiratory distress. Secondary end-points were proportion of subjects needing CPAP; CPAP (LoT); and change in respiratory distress score. RESULTS: Analysis by intention to treat (all subjects); median LoT (inter-quartile range, days): Heliox 1.90 (1.08–3.17), Airox 1.87 (1.11–3.34), P = .41. Facemask tolerant subgroup: Heliox 1.46 (0.85–1.95), Airox 2.01 (0.93–2.86), P = .03. Nasal cannula subgroup: Heliox 2.51 (1.21–4.32), Airox 2.81 (1.45–4.78), P = .53. Subgroup started on CPAP: Heliox 1.55 (1.38–2.01), Airox 2.26 (1.84–2.73), P = .02. Proportion of subjects needing CPAP: Heliox 17%, Airox 19%, O.R. 0.87 (0.47–1.60), P = .76. Heliox reduced respiratory distress score after 8 hours (mixed models estimate, −0.1298; P < .001). The effect was greater for facemask compared with nasal cannula (mixed models estimate, 0.093; P = .04). CONCLUSIONS: Heliox therapy does not reduce LoT unless given via a tight-fitting facemask or CPAP. Nasal cannula heliox therapy is ineffective.

Our aim was to evaluate the relationship between the degree of salvage following acute ST elevation myocardial infarction (STEMI) and subsequent reversible contractile dysfunction using cardiac magnetic resonance (CMR) imaging.Thirty-four patients underwent CMR examination 1-7 days after primary percutaneous coronary intervention (PPCI) for acute STEMI with follow-up at 1 year. The ischaemic area-at-risk (AAR) was assessed with T2-weighted imaging and myocardial necrosis with late gadolinium enhancement. Myocardial strain was quantified with complementary spatial modulation of magnetisation (CSPAMM) tagging.Ischaemic segments with poor (25 %) or intermediate (26-50 %) salvage index were associated with worse Eulerian circumferential (Ecc) strain immediately post-PPCI (-9.1 % ± 0.6, P = 0.033 and -11.8 % ± 1.3, P = 0.003, respectively) than those with a high (51-100 %) salvage index (-14.4 % ± 1.3). Mean strain in ischaemic myocardium improved between baseline and follow-up (-10.1 % ± 0.5 vs. -16.2 % ± 0.5 %, P0.0001). Segments with poor salvage also showed an improvement in strain by 1 year (-9.1 % ± 0.6 vs. -15.3 % ± 0.6, P = 0.033) although they remained the most functionally impaired.Partial recovery of peak systolic strain following PPCI is observed even when apparent salvage is less than 25 %. Late gadolinium enhancement (LGE) may not equate to irreversibly injured myocardium and salvage assessment performed within the first week of revascularisation may underestimate the potential for functional recovery.• MRI can measure how much myocardium is damaged after a heart attack. • Heart muscle that appears initially non-viable may sometimes partially recover. • Enhancement around the edges of infarcts may resolve over time. • Evaluating new cardio-protective treatments with MRI requires appreciation of its limitations.

In the article by M.B. Sikkel et al. (doi: 10.1002/jbio.201500193), published in J. Biophotonics 9, 311-323 (2016), an error occurred in the computer code that was used to generate Figure 3. This erratum is published to correct Figure 3, the calculated value of tgeom and the experimentally determined value of toptics in the text of the article.

Background: Critically ill patients frequently receive inadequate nutrition support as a result of under- or overfeeding. Malnutrition in intensive care unit (ICU) patients is associated with increased morbidity and mortality. The present study aimed to identify the significant factors that influence energy deficit in the ICU. Methods: ICU patients with a length of stay of ≥3 days were studied for 30 days over two consecutive years at a large university teaching hospital. Fifty-six Patients were studied, with a total of 530 records of feeding days. Information was collected for: day when feed initiated, age, gender, length of stay, Acute Physiological and Chronic Health Evaluation score (APACHE II), fed within 24 h, speciality, type of ventilation, feeding route, outcome (survived/died), diarrhoea (yes/no), aspirate volume, dietitian observed nutritional status (malnourished/not), sedation, estimated energy requirements and energy received. Mixed linear models for longitudinal data were used with energy deficit (energy received – energy requirements) as the dependent variable. Results: Factors that were found to have a significant association with energy deficit were: day feeding was initiated (P

In the presence of variant hepatic arterial anatomy, obtaining whole-liver coverage with yttrium 90 (Y90) radioembolization may be challenging. The purpose of this study was to determine whether a technique whereby variant hepatic arterial branches are embolized and then Y90 is administered selectively into one remaining hepatic arterial branch results in whole-liver coverage and effective therapy. A retrospective comparison of treatment response was made between a group of patients who underwent this technique before Y90 administration and a group of patients who received standard Y90 administration as a single dose into the proper hepatic artery or in divided doses into the immediate hepatic artery branches. The rest of the workup and treatment were identical in both groups, including routine embolization of potential nonhepatic, nontarget vessels (e.g., the gastroduodenal artery).A total of 32 patients (mean age 56.9 years, range 39-77 years) treated with Y90 between June 2004 and March 2008 were analyzed. The primary malignancy was colorectal in 29, breast in 2, and cholangiocarcinoma in 1. Group 1 comprised 20 patients who had no alterations to their hepatic arterial supply. Group 2 comprised 12 cases who had undergone prior embolization of hepatic arterial branches before administration of Y90. The response to treatment was assessed by comparing standardized uptake value (SUV) on the pre- and postprocedure fludeoxyglucose positron emission tomographic studies of representative lesions within the right and left lobes of the liver.In group 1, significant response (P0.001) was seen among right lobe lesions but not among left lobe lesions (P = 0.549). In group 2, there was a significant response among both right (P = 0.028) and left (P = 0.014) lobe lesions. No difference was found in the response of right lobe lesions (P = 0.726) between groups 1 and 2; a significantly greater response was found in group 2 compared to group 1 (P = 0.004) for left lobe lesions.Selective Y90 radioembolization after manipulation of hepatic arterial blood supply leads to an even distribution within the entire liver. When variations in hepatic arterial anatomy exist, this technique allows effective whole-liver radioembolization therapy from a single selective arterial injection.

Aims and methodTo compare an existing crisis resolution service with a new crisis resolution team (CRT) in Wales. The impact of the new team was measured by changes in bed days and admissions. A random sample of patients from each service was assessed for service satisfaction, social functioning and quality of life after first presentation.ResultsThe total number of bed days was reduced following the introduction of the new CRT (27.3%). The frequency and duration of compulsory admissions increased by 31% in the CRT between the first and second years and by 7% in the control service, offset by a greater reduction in informal admissions in the CRT (23.5%) compared with the control group (13.3%); overall bed usage was unchanged. Service satisfaction, social functioning and quality of life showed no important differences between the services.Clinical implicationsCrisis resolution teams may reduce informal admissions in the short term but at the cost of more compulsory admissions later.

Background. This study investigates whether exploitation of circadian variation in heart rate-adjusted QT interval (QTc) is an alternative to the inclusion of a positive control as a method for demonstrating assay sensitivity in a phase 1 clinical trial.Methods. Electrocardiograms (ECGs) from a dose-escalating placebo-controlled phase 1 clinical trial were analyzed. The trial included 63 healthy young males in 7 cohorts; each had 17 ECGs recorded. The 21 subjects receiving placebo were studied: hierarchical linear model analysis was conducted with the measurements across a 43-hour time period nested within subjects. Separate analyses were conducted with QTcBazett, QTcFridericia, QTcFramingham, and a QT-heart rate z score as the dependent variable.Results. Pairwise contrasts between the time points 6 and 10 hours after the administration of the placebo showed a difference of 15.97 ms (CI 9.58-22.37), 8.17 ms (CI 3.47-12.88), 10.77 ms (CI 5.70-15.84), and 0.39 (equivalent to 8 ms CI 0.16-0.62) for QTcBazett...

Objective To assess psychiatric status after meningococcal disease. Method Cohort study of 66 children (34 boys, 32 girls) ages 4 to 17 years admitted to pediatric hospitals with meningococcal disease. The main outcome measure was psychiatric disorder (1-year period and point prevalence on the Schedule for Affective Disorders and Schizophrenia for School-Age Children interview for children 6 years or older; point prevalence in younger children on the Behavior Screening Questionnaire). Results During the course of the year after discharge from hospital, psychiatric disorders were identified in 23 of 40 (57%) children ages 6 years or older. The most common primary disorders were depressive, oppositional defiant, and anxiety disorders. At the time of 12-month follow-up, psychiatric disorders were present in 13 of 40 (32%) of those ages 6 or older and in 7 of 26 (26%) under 6 years old. Two children had a diagnosis of posttraumatic stress disorder. Logistic regression analysis showed that global meningococcal illness severity score, clinical shock on admission, and impairing premorbid emotional and behavioral problems in the child were independent predictors of psychiatric disorder at 12-month follow-up. Conclusions Psychiatric disorders are common in the year after meningococcal disease. Especially at risk are children who are severely medically ill and those with more impairing premorbid emotional and behavioral problems.

Oblique plane microscopy (OPM) is a form of light sheet microscopy that uses a single high numerical aperture microscope objective for both fluorescence excitation and collection. In this paper, measurements of the relative collection efficiency of OPM are presented. An OPM system incorporating two sCMOS cameras is then introduced that enables single isolated cardiac myocytes to be studied continuously for 22 seconds in two dimensions at 667 frames per second with 960 × 200 pixels and for 30 seconds with 960 × 200 × 20 voxels at 25 volumes per second. In both cases OPM is able to record in two spectral channels, enabling intracellular calcium to be studied via the probe Fluo‐4 AM simultaneously with the sarcolemma and transverse tubule network via the membrane dye Cellmask Orange. The OPM system was then applied to determine the spatial origin of spontaneous calcium waves for the first time and to measure the cell transverse tubule structure at their point of origin. Further results are presented to demonstrate that the OPM system can also be used to study calcium spark parameters depending on their relationship to the transverse tubule structure. figureWiley-VCH Verlag & Co.KGaA

To assess whether susceptibility-weighted imaging (SWI) provides better image contrast for the detection of haemorrhagic ischaemia-reperfusion injury in the heart.Thirty patients (all men; mean age 53 years) underwent cardiac magnetic resonance imaging (MRI) within 7 days of primary percutaneous intervention for acute ST elevation myocardial infarction (STEMI). Multiple gradient-echo T2* sequences with magnitude and phase reconstructions were acquired. A high-pass filtered phase map was used to create a mask for the SWI reconstructions. The difference in image contrast was assessed in those patients with microvascular obstruction. A mixed effects regression model was used to test the effect of echo time and reconstruction method on phase and contrast-to-noise ratio (CNR). Medians and interquartile ranges (IQR) are reported.T2* in haemorrhagic infarcts was shorter than in non-haemorrhagic infarcts (33.5 ms [24.9-43] versus 49.9 ms [44.6-67.6]; p=0.0007). The effect of echo time on phase was significant (p0.0001), as was the effect of haemorrhage on phase (p=0.0016). SWI reconstruction had a significant effect on the CNR at all echo times (echoes 1-5, p0.0001; echo 6, p=0.01; echo 7, p=0.02). The median echo number at which haemorrhage was first visible was less for SWI compared to source images (echo 2 versus echo 5, p=0.0002).Cardiac SWI improves the contrast between myocardial haemorrhage and the surrounding tissue following STEMI and has potential as a new tool for identifying patients with ischaemia-reperfusion injury.

Background— Ventricular arrhythmias occur more frequently in heart failure during episodes of ischemia–reperfusion although the mechanisms underlying this in humans are unclear. We assessed, in explanted human hearts, the remodeled electrophysiological response to acute ischemia–reperfusion in heart failure and its potential causes, including the remodeling of metabolic gene expression. Methods and Results— We optically mapped coronary-perfused left ventricular wedge preparations from 6 human end-stage failing hearts (F) and 6 donor hearts rejected for transplantation (D). Preparations were subjected to 30 minutes of global ischemia, followed by 30 minutes of reperfusion. Failing hearts had exaggerated electrophysiological responses to ischemia–reperfusion, with greater action potential duration shortening ( P P =0.001 at 12-minute ischemia) and greater conduction slowing during ischemia, delayed recovery of electric excitability after reperfusion (F, 4.8±1.8 versus D, 1.0±0 minutes; P SLC27A4 and KCNJ11 significantly downregulated at a false discovery rate of 0%. Conclusions— We demonstrate, for the first time in human hearts, that the electrophysiological response to ischemia–reperfusion in heart failure is accelerated during ischemia with slower recovery after reperfusion. This can enhance spatial conduction and repolarization gradients across the ischemic border and increase arrhythmia susceptibility. This adverse response was associated with downregulation of expression of cardiac metabolic genes.

To the Editor: Hydrogen sulfide (H2S) has emerged as a new and important endogenous regulator of inflammation in recent years [1] and may also protect from emphysema induced by cigarette smoke exposure [2]. We have also recently shown that H2S can inhibit airway smooth muscle cell proliferation and inflammatory mediator release in vitro [3]. Serum levels of H2S positively correlate with the decline in lung function in chronic obstructive pulmonary disease (COPD) and were significantly lower in Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage III patients compared with those in GOLD I [4]. Existing therapies for COPD, such as corticosteroids or long-acting anticholinergic agents, may reduce the exacerbation rate but do not significantly slow disease progression. A previous study has shown that theophylline alone had no impact on serum H2S levels and is of limited value in the management of stable COPD [5]. Interestingly, sputum H2S measured in patients with asthma correlated with sputum neutrophil counts and the degree of airflow obstruction measured by forced expiratory volume in 1 s (FEV1) % predicted [6]. Moreover, combination therapy of an inhaled glucocorticoid with low-dose theophylline has been shown to attenuate airway inflammation in patients with COPD and reverse glucocorticoid resistance [7]. We therefore investigated whether the combination of inhaled corticosteroid and low-dose theophylline, as opposed to …

We read the article by Coppini et al1 with great interest. The insight that they provide into the electrophysiological phenotype of the cardiomyocyte in hypertrophic cardiomyopathy was made all the more convincing because of their use of robust hierarchical statistical methodologies for significance testing. Statistical significance testing is now almost ubiquitous in basic cardiovascular science studies and allows decisions to be made on the basis of the data collected and their critical and analytic appraisal. However, one important factor that is commonly ignored in otherwise first-class research is the hierarchical …

Background Many factors affect the blood metal ion levels after metal-on-metal (MOM) hip arthroplasty. The main surgically adjustable variable is the amount of coverage of the head provided by the cup which is a function of the inclination and version angles. However, most studies have used plain radiographs which have questionable precision and accuracy, particularly for version and large diameter metal heads; further, these studies do not simultaneously assess version and inclination. Thus the relationship between version and blood metal ions levels has not been resolved.

Introduction Anti-vehicle (AV) mines have been laid indiscriminately in conflict areas for the past 100 years. With an indeterminate life-span they continue to pose a significant threat to the civilian population, as well as restrict the movement of people, aid and goods to vulnerable populations. The aim of this study was to analyse unique casualty data from 2212 mine incidents to determine if simple vehicle modifications can reduce fatality and injury rates from mine explosions. Method We analysed casualty data from the Rhodesian War (1972–1980), to assess the effects of basic vehicle modifications (V-shaped hull, increased ground clearance, widened axles, heavy vehicles and blast deflectors) on injury rates. A multinomial regression statistical model was developed for vehicle modifications and number of alterations to explore these effects. Results Incident data was available on 2212 vehicle mine incidents involving 16,456 people. The overall fatality rate was 3.3% (544/16,456) and the overall injury rate was 22.7% (3741/16,456). Explosions against mine-protected vehicles resulted in a fatality rate of 1.2% (150/12,919); occupants in unprotected vehicles sustained a fatality rate of 11.4% (395/3537). The injury rate in mine protected vehicles was 22.2% (2868/12,919) compared to 24.7% in unprotected vehicles (873/3537). Utilising a multinomial logistical-regression model, we show that each design feature significantly reduced fatality rate (from 45% in unprotected vehicles to 0.8% in protected vehicles); each of these designs had a cumulative effect in fatality reduction. In isolation, blast deflectors, whilst reducing fatality rates, increased injury rates. Conclusions Our data clearly demonstrates that simple vehicle modifications can have a significant effect on reducing fatality and injury rates from AV mine explosions. Given that the modifications described were produced using commercially available vehicles with basic engineering requirements, we believe that similar processes could be employed in post-conflict environments in a cost-effective manner.

Inhaled corticosteroids (ICS) have proved disappointing at reducing airway inflammation in COPD. However, previous studies indicate that low doses of theophylline enhance the activity of a key corticosteroid-associated corepressor protein, histone deacetylase (HDAC)2, which is reduced in COPD. This may account, at least in part, for the relative corticosteroid resistance. Thus, combination therapy with an ICS and low-dose theophylline may be of benefit in the treatment of COPD.To test the hypothesis that ICS and theophylline have a greater therapeutic effect than theophylline alone, 30 patients with COPD were treated with placebo theophylline capsules and either inhaled fluticasone propionate (FP) (500 microg bid) or inhaled placebo for 4 weeks in a double-dummy, randomized, double-blind, parallel study. After a 2-week washout, patients were given active theophylline capsules (plasma level of 8.8-12.4 mg/L).In an across-arm comparison, combination treatment with FP and theophylline did not reduce total sputum neutrophils but significantly reduced total sputum eosinophils (P.05). Additional across-arm comparisons suggest a further reduction in percentage sputum neutrophils and sputum chemokine (C-X-C motif) ligand 8/IL-8 (P.05). Furthermore, within-arm observational data also demonstrated increases in forced midexpiratory flow rate and FEV(1)% predicted (P.05) following combination treatment only. In an open-label study, low-dose theophylline when added to inhaled FP increased total HDAC activity in peripheral blood monocytes ninefold (P.01) compared with FP alone from the same patients with COPD.Combination therapy with an inhaled corticosteroid and low-dose theophylline may attenuate airway inflammation in patients with COPD.clinicaltrials.gov; Identifier NCT00241631.

Objective: To quantify levels of engagement and retention in specialist services for people with personality disorder (PD). Method: Demographic and clinical data were collected on referrals to 10 specialist services for people with PD. Follow-up data on retention and drop-out from services were collected over the following 30 months. Results: Seven hundred and thirteen (60.1%) of 1186 people referred to services were taken by them, of whom 164 (23.0%) subsequently dropped out prior to the completion of an episode of care. Men, younger people and those with higher levels of personality disturbance were less likely to complete a package of care. Conclusion: Specialist community-based services for adults with PD are able to engage most of those that are referred to them, but further efforts need to be made to find ways to engage younger people and men with PD.

ObjectivesThe purpose of this study was to determine the morphologic and physiological predictors of post-natal surgical pathway in a longitudinal series of fetuses with pulmonary atresia with intact ventricular septum (PAIVS) and/or critical pulmonary stenosis with reversal of ductal flow (CPS) using statistical modeling.BackgroundPulmonary atresia with intact ventricular septum is rarely associated with chromosomal or extra cardiac malformations, so decisions about continuing a pregnancy are strongly influenced by the prediction of univentricular (UV) or biventricular (BV) circulation.MethodsPredictive scores were derived, using a combination of z-scores of fetal cardiac measurements (for femoral length) and tricuspid/mitral valve (TV/MV) ratios, to facilitate early prediction of UV or BV circulation in 21 fetuses with PAIVS (18 fetuses) or CPS (3 fetuses) between 1998 and 2004. We also assessed the predictive value of coronary fistulae and right atrial pressure (RAP) score (comprising the tricuspid valve, foramen ovale, and ductus venosus Doppler).ResultsOne-half of the cohort was first assessed before 23 gestational weeks (range 15.7 to 33.7 weeks). The TV z-score was a good predictor at all gestations, but the best predictive scores for specific gestations were pulmonary valve (PV) z-score (31 weeks). The RAP score and coronary fistulae were good independent predictors: RAP score >3 predicted BV with area under the curve of 0.833, and detection of fistulae usually predicted a UV route.ConclusionsThe best predictive scores for post-natal outcome in fetal PAIVS/CPS are a combination of morphologic and physiological variables, which predict a BV circulation with a sensitivity of 92% and specificity of 100% before 26 weeks.

Background: Critically ill patients frequently receive inadequate nutrition support due to under- or overestimation of nutritional needs (Reid, 2006), delays in initiating nutrition support and frequent interruptions to nutritional support (Heyland et al., 2003). The purpose of this research was to identify the significant factors which influence energy deficit in the adult intensive care unit (ICU). Methods: ICU patients with a length of stay of ≥3 days were studied for 30 days over two consecutive years at a large university teaching hospital. Fifty-six patients were studied with a total of 530 records of feeding days. The following information was collected: day feeding was initiated, age, length of stay, Acute Physiology & Chronic Health Evaluation score (APACHE II), fed within 24 h (yes/no) gender, speciality, type of ventilation (endotracheal tube (ETT), tracheostomy, non-invasive (NIV), self), feeding route, outcome (survived/died), diarrhoea, aspirate volume, dietitian observed nutritional status (at risk or not), sedation, estimated energy requirements and energy received. The statistical method used was mixed linear models for longitudinal data with energy deficit (energy received – energy requirements) as the dependent variable. Results: The model showed that factors which significantly affected energy deficit were: day feeding was initiated (P

CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO Esta tese propõe um modelo para o tratamento de observações diárias e é aplicado na área do setor elétrico, no problema de previsão de carga horária. O modelo proposto é basicamente um modelo estrutural onde a sazonalidade anual (movimentos periódicos dentro do ano) é modelada utilizando a técnica de Splines. Esta técnica também é utilizada na estimação do efeito não linear de uma variável explicativa. O modelo desenvolvido nesta tese também leva em conta os feriados dada a grande influência dos mesmos no consumo de energia elétrica. A metodologia proposta é aplicada à três concessionárias do Sistema Interligado Brasileiro: LIGHT (Estado do Rio de Janeiro); CEMIG (Estado de Minas Gerais) e COPEL (Estado do Paraná). A estimação é levada a cabo utilizando o software STAMP conjuntamente com módulos desenvolvidos no utilitário MATLAB. This thesis presents a model that deals with daily obsevations applied to the problem of forecasting daily elecricity demand. This approach is basaed on a structural time series model with the annual seasonal pattern being modelled by a Periodic Sppline. The methods of Splines was first used in Harvey and Koopman (1993) to analyse hourly load observations, including temperature used an explanatory variable which is also modelled by a Spline. The main contribuition of this thesis is the treatment of holidays and the temperature response modelled by a spline which considerss the possible vsariations that the effect of temperature has on electricity demand within the year. The methodology is applied to three companies of the Brazilian electrical system: LIGHT (State of Rio de Janeiro), CEMIG (State of Minas Gerais) and COPEL (state of Paraná).

Background Information technology is finding an increasing role in the training of medical students. We compared information recall and student experience and preference after live lectures and video podcasts in undergraduate medical education. Methods We performed a crossover randomised controlled trial. 100 students were randomised to live lecture or video podcast for one clinical topic. Live lectures were given by the same instructor as the narrator of the video podcasts. The video podcasts comprised Powerpoint™ slides narrated using the same script as the lecture. They were then switched to the other group for a second clinical topic. Knowledge was assessed using multiple choice questions and qualitative information was collected using a questionnaire. Results No significant difference was found on multiple choice questioning immediately after the session. The subjects enjoyed the convenience of the video podcast and the ability to stop, review and repeat it, but found it less engaging as a teaching method. They expressed a clear preference for the live lecture format. Conclusions We suggest that video podcasts are not ready to replace traditional teaching methods, but may have an important role in reinforcing learning and aiding revision.