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The conventional tracking control of mechanical systems is generally based on the stabilization of error dynamics and most of the results can only guarantee asymptotic tracking of the desired trajectories. Since error dynamics are generally time-varying, it is very difficult to find appropriate Lyapunov functions or control Lyapunov functions to complete stability analysis and controller design. To address this limitation, the novel constructive exponential tracking control method is proposed to mechanical systems by utilizing the Hamiltonian realization and contraction analysis in this paper. Firstly, based on the Hamiltonian realization and use the structural characteristics of port-Hamiltonian systems, the exponential tracking controllers are constructed for fully actuated and under-actuated mechanical systems by combining the pre-feedback with feedback control. The proposed tracking control strategies can be used to discuss fully actuated and under-actuated mechanical systems in a unified framework. Then the exponential decay-rate of tracking controllers and procedure for selecting control parameters for fully actuated and under-actuated mechanical systems are given. Finally, comparative simulations and experiments are carried out to illustrate the effectiveness and robustness of the proposed control strategy. • Utilizing the Hamiltonian realization and contraction analysis method, novel constructive exponential tracking control strategies are proposed to mechanical systems by combining the pre-feedback with feedback control. • The exponential decay-rate and the control parameter selection procedure of tracking controllers for fully actuated and under-actuated mechanical systems are obtained. • The proposed constructive tracking control strategies can be used to discuss fully actuated and under-actuated mechanical systems in a unified framework. [ABSTRACT FROM AUTHOR]

To assess insulin glargine 100 U/mL (IGlar-100) treatment outcomes according to newly-defined subgroups of type 2 diabetes mellitus (T2DM). Insulin-naïve T2DM participants (n = 2684) from nine randomised clinical trials initiating IGlar-100 were pooled and assigned to subgroups "Mild Age-Related Diabetes (MARD)" , "Mild Obesity Diabetes (MOD)" , " Severe Insulin Resistant Diabetes (SIRD)" , and " Severe Insulin Deficient Diabetes (SIDD)" , according to age at onset of diabetes, baseline HbA1c, BMI, and fasting C-peptide using sex-specific nearest centroid approach. HbA1c, FPG, hypoglycemia, insulin dose, and body weight were analysed at baseline and 24 weeks. Subgroup distribution was MARD 15.3 % (n = 411), MOD 39.8 % (n = 1067), SIRD 10.5 % (n = 283), SIDD 34.4 % (n = 923). From baseline HbA1c 8.0–9.6% adjusted least square mean reductions after 24 weeks were similar between subgroups (1.4–1.5 %). SIDD was less likely to achieve HbA1c < 7.0 % (OR: 0.40 [0.29, 0.55]) than MARD. While the final IGlar-100 dose (0.36 U/kg) in MARD was lower than in other subgroups (0.46–0.50 U/kg), it had the highest hypoglycemia risk. SIRD had lowest hypoglycemia risk and SIDD exhibited greatest body weight gain. IGlar-100 lowered hyperglycemia similarly in all T2DM subgroups, but level of glycemic control, insulin dose, and hypoglycemia risk differed between subgroups. • Response to basal insulin treatment in newly-defined diabetes subgroups is unknown. • Adjusted HbA1c and FPG reductions with IGlar-100 were similar in T2DM subgroups. • MARD achieved best and SIDD least glycaemic control with IGlar-100 at 24 weeks. • IGlar-100 dose at 24 weeks differed considerably between MARD and other subgroups. • SIRD experienced the lowest hypoglycaemia risk compared to other T2DM subgroups. [ABSTRACT FROM AUTHOR]

Background: Preparticipation screening for conditions associated with sudden cardiac death (SCD) is required in college athletes. Previous cost analyses used theoretical models based on variable assumptions, but no study used real-life outcomes.Objective: The purpose of this study was to compare disease prevalence, positive findings, and costs of 2 different screening strategies: history and physical examination alone (H&P) or with an electrocardiogram (H&P+ECG).Methods: De-identified preparticipation data (2009-2017) from Pacific-12 Conference institutions were abstracted for cardiovascular history questions, cardiovascular physical examination, and ECG result. Secondary testing, cardiac diagnoses, return to play outcomes, and complications from testing were recorded. The costs of screening and secondary testing were based on the Centers for Medicare & Medicaid Services Physician Fee Schedule.Results: A total of 8602 records (4955 H&P, 3647 H&P+ECG) were included. Eleven conditions associated with SCD were detected (2 H&P only, 9 H&P+ECG). The prevalence of cardiovascular conditions associated with SCD discovered with H&P alone was 0.04% (1/2454) compared to 0.24% (1/410) when ECG was added (P = .01) (odds ratio 5.17; 95% confidence interval 1.28-20.85; P = .02). Cost of screening and secondary testing with H&P alone was $130 per athlete and in the ECG-added group was $152 per athlete. The cost per diagnosis was $312,407 in the H&P group and $61,712 in the ECG-added group. There were no adverse outcomes from secondary testing or treatment.Conclusion: H&P with the addition of ECG is 6 times more likely to detect a cardiovascular condition associated with SCD than without. The addition of ECG improves the cost efficiency per diagnosis by 5-fold and should be considered at college institutions with appropriate resources. [ABSTRACT FROM AUTHOR]

Background: Electrocardiogram (ECG) screening in athletes enhances the detection of conditions associated with sudden cardiac death (SCD), but concerns remain for false positive results when conducted outside of specialized centers. This study compared ECG interpretation in college athletes between local physicians and a sports cardiology center (SCC).Methods: Screening ECGs in athletes from eight Pacific-12 Conference institutions performed between 2010 and 2016 were included. Local interpretation was compared to SCC interpretation using both the Seattle Criteria (SCC-SC) and the International Criteria (SCC-IC).Results: A total of 2445 athlete ECGs (mean age 18.5 years; 57.1% male; 63.2% Caucasian and 15.3% African American) were reviewed. The proportion of ECGs classified as abnormal was similar between local and SCC-SC interpretation (3.5% vs. 3.4%, respectively; p = .94), but was lower by SCC-IC interpretation (1.5%, p < .001). ECG abnormalities interpreted as normal by local physicians but as abnormal by SCC-SC (n = 33) and SCC-IC (n = 16) standards included: pathological Q waves (n = 15 SCC-SC; n = 3 SCC-IC), T-wave inversions (n = 8 both), and ST-depressions (n = 3 both). There was a 97.5% ECG interpretation agreement and substantial interobserver reliability (k = 0.611, p < .001) between local and SCC-SC interpretation in athletes screened starting one year after publication of the Seattle Criteria (n = 1388). Both local and SCC physicians correctly identified six abnormal ECGs associated with conditions at risk of SCD.Conclusions: ECG interpretation by local physicians at college universities had similar accuracy compared to a specialized SCC with a low overall abnormal rate, similar sensitivity, and substantial interobserver reliability. Uniform application of current ECG interpretation standards is recommended to further improve accuracy. [ABSTRACT FROM AUTHOR]

There is inconsistent evidence supporting the self-monitoring of blood glucose (SMBG) in people with non-insulin treated type 2 diabetes (T2D). Structured SMBG protocols have a greater impact on glycaemic control than unstructured SMBG and may improve measures of glycaemic variability (GV), though few previous studies have reported on specific GV outcomes. Our aim was to determine the impact of structured SMBG on simple measures of GV in people with T2D. Participants undertook structured SMBG over 12 months, with HbA 1c recorded at baseline and at 3-monthly follow-up. For each participant, the mean blood glucose (MBG), fasting blood glucose (FBG), standard deviation BG (SD-BG), coefficient of variation of BG (CV-BG), mean absolute glucose change (MAG) and HbA 1c were determined for each 3-month period. Responders were participants with an improvement in HbA 1c of ≥5 mmol/mol (0.5%) over 12 months. Data from two hundred and thirty-one participants were included for analysis. Participants had a baseline median [interquartile range] HbA 1c 68.0 [61.5–75.5] mmol/mol (8.4%). Participants demonstrated significant improvements in the MBG (−1.25 mmol/L), FBG (−0.97 mmol/L), SD-BG (−0.44 mmol/L), CV-BG (−1.43%), MAG (−0.97 mmol/L), and HbA 1c (−7.0 mmol/mol) (all p < 0.001) at 12 months compared to these measures collected within the first 3 months of SMBG. Responders had a significantly higher baseline median [interquartile range] HbA 1c of 70.0 [63.0–78.0] mmol/mol compared to 61.0 [56.5–66.0] mmol/mol in non-responders (P < 0.001). Structured SMBG improved all the observed measures of GV. These results support the use of structured SMBG in people with non-insulin treated T2D. • This secondary analysis of the SMBG study explores the impact of structured SMBG on glycaemic variability (GV) in people with T2D. • There were significant improvements observed in several measures of GV over the 12-month study period. • Participants with poorer baseline glycaemic control were more likely to achieve a significant response to SMBG. • These data add significantly to the existing literature about the impact of structured SMBG on GV in people with T2D. [ABSTRACT FROM AUTHOR]

Aims: Evaluate efficacy and hypoglycaemia according to concomitant oral antidiabetes drug (OAD) in people with type 2 diabetes initiating insulin glargine 100U/mL (Gla-100) or neutral protamine Hagedorn (NPH) insulin once daily.Methods: Four studies (target fasting plasma glucose [FPG] ⩽100mg/dL [⩽5.6mmol/L]; duration ⩾24weeks) were included. Standardised data from 2091 subjects (Gla-100, n=1024; NPH insulin, n=1067) were analysed. Endpoints included glycated haemoglobin (HbA1c) and FPG change, glycaemic target achievement, hypoglycaemia, weight change, and insulin dose.Results: Mean HbA1c and FPG reductions were similar with Gla-100 and NPH insulin regardless of concomitant OAD (P=0.184 and P=0.553, respectively) and similar proportions of subjects achieved HbA1c <7.0% (P=0.603). There was a trend for more subjects treated with Gla-100 achieving FPG ⩽100mg/dL versus NPH insulin (relative risk [RR] 1.09 [95% confidence interval (CI) 0.97-1.23]; P=0.135). Plasma glucose confirmed (<70mg/dL) overall and nocturnal hypoglycaemia incidences and rates were lower with Gla-100 versus NPH insulin (overall RR 0.93 [95% CI 0.87-1.00]; P=0.041; nocturnal RR 0.73 [95% CI 0.65-0.83]; P<0.001). After 24weeks, weight gain and insulin doses were higher with Gla-100 versus NPH insulin (2.7kg vs 2.3kg, P=0.009 and 0.42U/kg vs 0.39U/kg; P=0.003, respectively). Insulin doses were higher when either insulin was added to sulfonylurea alone.Conclusions: Pooled results from treat-to-target trials in insulin-naïve people with type 2 diabetes demonstrate a significantly lower overall and nocturnal hypoglycaemia risk across different plasma glucose definitions with Gla-100 versus NPH insulin at similar glycaemic control. OAD therapy co-administered with Gla-100 or NPH insulin impacts glycaemic control and overall nocturnal hypoglycaemia risk. [ABSTRACT FROM AUTHOR]

Objective Static 3-dimensional printing is used for operative planning in cases that involve difficult anatomy. An interactive 3D print allowing deliberate surgical practice would represent an advance. Methods Two patients with hypertrophic cardiomyopathy had 3-dimensional prints constructed preoperatively. Stereolithography files were generated by segmentation of chest computed tomographic scans. Prints were made with hydrogel material, yielding tissue-like models that can be surgically manipulated. Septal myectomy of the print was performed preoperatively in the simulation laboratory. Volumetric measures of print and patient resected specimens were compared. An assessment tool was developed and used to rate the utility of this process. Clinical and echocardiographic data were reviewed. Results There was congruence between volumes of print and patient resection specimens (patient 1, 3.5 cm 3 and 3.0 cm 3 , respectively; patient 2, 4.0 cm 3 and 4.0 cm 3 , respectively). The prints were rated useful (3.5 and 3.6 on a 5-point Likert scale) for preoperative visualization, planning, and practice. Intraoperative echocardiographic assessment showed adequate relief of left ventricular outflow tract obstruction (patient 1, 80 mm Hg to 18 mm Hg; patient 2, 96 mm Hg to 9 mm Hg). Both patients reported symptomatic improvement (New York Heart Association functional class III to class I). Conclusions Three-dimensional printing of interactive hypertrophic cardiomyopathy heart models allows for patient-specific preoperative simulation. Resection volume relationships were congruous on both specimens and suggest evidence of construct validity. This model also holds educational promise for simulation of a low-volume, high-risk operation that is traditionally difficult to teach. [ABSTRACT FROM AUTHOR]

Aims: To evaluate the efficacy and safety of adding a single bolus dose of insulin glulisine to basal insulin ('basal-plus') in persons with type 2 diabetes.Methods: Data from patients with poor glycemic control on oral antihyperglycemic drugs who were initiated on a 'basal-plus' regimen for up to 6 months were pooled from four randomized, multicenter studies. Glycated hemoglobin (HbA1c), fasting blood glucose, postprandial glucose (PPG), insulin dose and demographics were measured at baseline and end of study.Results: 711 patients with a mean age of 59.9 years and a mean duration of diabetes of 11.0 years were included in the analysis population. A 'basal-plus' regimen was associated with significant decreases in HbA1c and PPG at 6 months, an increase in glargine and glulisine doses and small, but statistically significant, changes in body weight and BMI in all patient subsets. The proportion of patients with HbA1c<7% also increased in all populations studied, while the prevalence of severe hypoglycemia was low and did not significantly differ across patient groups.Conclusions: These results suggest that the use of 'basal-plus' can achieve a good therapeutic response with a low risk of hypoglycemia and weight gain, regardless of a patient's age or BMI. [ABSTRACT FROM AUTHOR]

Phosphoinositide-dependent kinase-1 (PDK1) is a key signaling molecule downstream of the phosphatidylinositol 3-kinase pathway and is a master regulator of multiple kinases in cells of epithelial and hematopoietic lineages. The physiological role of PDK1 in regulating skin and immune homeostasis is not known. Here we developed a mouse model in which PDK1 is conditionally ablated in activated CD4 T cells, regulatory T cells, and mature keratinocytes through OX40-Cre recombinase expression. The resultant mice (PDK1-CKO) spontaneously developed severe dermatitis, skin fibrosis, and systemic T helper type 2 immunity, succumbing by 11 weeks of age. Through a series of T-cell transfers, bone marrow reconstitutions, and crossing to lymphocyte-deficient backgrounds, we demonstrate that ablation of PDK1 in keratinocytes is the major driver of disease pathogenesis. PDK1-deficient keratinocytes exhibit intrinsic defects in the expression of key structural proteins including cytokeratin-10 and loricrin, resulting in increased keratinocyte turnover, which in turn triggers inflammation, T-cell recruitment, and immune-mediated destruction. Our results reveal PDK1 as a central regulator of keratinocyte homeostasis that prevents skin immune infiltration and inflammation. [ABSTRACT FROM AUTHOR]

Aim Evaluate early (0–12 weeks) and later (12–24 weeks) treatment outcomes in subjects with type 2 diabetes not achieving glycaemic control with oral antidiabetes drugs (OADs). Methods Selected data were pooled from 15 randomised, controlled treat-to-target (fasting plasma glucose < 100 mg/dL [<5.6 mmol/L]) trials adding insulin glargine to metformin, a sulphonylurea, or both. Glycaemic and hypoglycaemia parameters, insulin dose, and body weight at weeks 12 and 24 were assessed using individualised subject-level data. Results Data from 2837 subjects were analysed. HbA1c decreased from 8.8% (73 mmol/mol) at baseline by 1.4% (15 mmol/mol) at Week 12, and a further 0.2% (2 mmol/mol) at Week 24 in the pooled population. Similar reductions were observed across the different treatment groups. HbA1c < 7.0% (<53 mmol/mol) was reached by 34.8% of participants at Week 12 and an additional 24.3% by Week 24. Hypoglycaemia incidence and rates were similar during the early and continued treatment periods across all treatment combinations, but were markedly lower for insulin glargine plus metformin versus the other 2 regimens. Conclusions Early and sustained glycaemic benefits with a low-risk of hypoglycaemia are observed after initiation of insulin glargine in a pooled type 2 diabetes cohort previously uncontrolled on OADs. [ABSTRACT FROM AUTHOR]

The first insulin preparation injected in humans in 1922 was short-acting, extracted from animal pancreas, contaminated by impurities. Ever since the insulin extracted from animal pancreas has been continuously purified, until an unlimited synthesis of regular human insulin (RHI) became possible in the '80s using the recombinant-DNA (rDNA) technique. The rDNA technique then led to the designer insulins (analogs) in the early '90s. Rapid-acting insulin analogs were developed to accelerate the slow subcutaneous (sc) absorption of RHI, thus lowering the 2-h post-prandial plasma glucose (PP-PG) and risk for late hypoglycemia as comparing with RHI. The first rapid-acting analog was lispro (in 1996), soon followed by aspart and glulisine. Rapid-acting analogs are more convenient than RHI: they improve early PP-PG, and 24-h PG and A1C as long as basal insulin is also optimized; they lower the risk of late PP hypoglycemia and they allow a shorter time-interval between injection and meal. Today rapid-acting analogs are the gold standard prandial insulins. Recently, even faster analogs have become available (faster aspart, ultra-rapid lispro) or are being studied (Biochaperone lispro), making additional gains in lowering PP-PG. Rapid-acting analogs are recommended in all those with type 1 and type 2 diabetes who need prandial insulin replacement. • The first insulin preparation injected in humans in 1922 was short-acting extracted from animal pancreas. • Rapid-acting insulin analogs accelerate the sc absorption of regular insulin improving prandial control. • Rapid-acting insulin analogs reduce interprandial hypoglycemia and improve the 24-h PG if basal insulin is optimized. • Faster analogs (faster aspart, ultra-rapid lispro, Biochaperone lispro) allow even shorter time injection-meal. [ABSTRACT FROM AUTHOR]

The industry's recent challenges in a dramatically changing environment can occasionally result in calls for local governments to consider municipalization of local power resources. But simply changing the ownership structure of shareholder-owned electric companies and turning them into public utilities offer a false sense of progress, when what is truly needed is investment in new technologies, the nation's transmission grid and distribution systems, and new approaches. [Copyright &y& Elsevier]

Summary: In mammalian skin, Merkel cells are mechanoreceptor cells that are required for the perception of gentle touch. Recent evidence indicates that mature Merkel cells descend from the proliferative layer of skin epidermis; however, the stem cell niche for Merkel cell homeostasis has not been reported. Here, we provide genetic evidence for maintenance of mature Merkel cells during homeostasis by Krt17+ stem cells located in epidermal touch domes of hairy skin and in the tips of the rete ridges of glabrous skin. Lineage tracing analysis indicated that the entire pool of mature Merkel cells is turned over every 7–8 weeks in the adult epidermis and that Krt17+ stem cells also maintain squamous differentiation in the touch dome and in glabrous skin. Finally, selective genetic ablation of Krt17+ touch-dome keratinocytes indicates that these cells, and not mature Merkel cells, are primarily responsible for maintaining innervation of the Merkel cell-neurite complex. Video Abstract: Display Omitted [Copyright &y& Elsevier]

Objectives: This study sought to test whether aortic valve calcium (AVC) is independently associated with coronary and cardiovascular events in a primary-prevention population. Background: Aortic sclerosis is associated with increased cardiovascular morbidity and mortality among the elderly, but the mechanisms underlying this association remain controversial. Also, it is unknown whether this association extends to younger individuals. Methods: We performed a prospective analysis of 6,685 participants in MESA (Multi-Ethnic Study of Atherosclerosis). All subjects, ages 45 to 84 years and free of clinical cardiovascular disease at baseline, underwent computed tomography for AVC and coronary artery calcium scoring. The primary, pre-specified combined endpoint of cardiovascular events included myocardial infarctions, fatal and nonfatal strokes, resuscitated cardiac arrest, and cardiovascular death, whereas a secondary combined endpoint of coronary events excluded strokes. The association between AVC and clinical events was assessed using Cox proportional hazards regression with incremental adjustments for demographics, cardiovascular risk factors, inflammatory biomarkers, and subclinical coronary atherosclerosis. Results: Over a median follow-up of 5.8 years (interquartile range: 5.6 to 5.9 years), adjusting for demographics and cardiovascular risk factors, subjects with AVC (n = 894, 13.4%) had higher risks of cardiovascular (hazard ratio [HR]: 1.50; 95% confidence interval [CI]: 1.10 to 2.03) and coronary (HR: 1.72; 95% CI: 1.19 to 2.49) events compared with those without AVC. Adjustments for inflammatory biomarkers did not alter these associations, but adjustment for coronary artery calcium substantially attenuated both cardiovascular (HR: 1.32; 95% CI: 0.98 to 1.78) and coronary (HR: 1.41; 95% CI: 0.98 to 2.02) event risk. AVC remained predictive of cardiovascular mortality even after full adjustment (HR: 2.51; 95% CI: 1.22 to 5.21). Conclusions: In this MESA cohort, free of clinical cardiovascular disease, AVC predicts cardiovascular and coronary event risk independent of traditional risk factors and inflammatory biomarkers, likely due to the strong correlation between AVC and subclinical atherosclerosis. The association of AVC with excess cardiovascular mortality beyond coronary atherosclerosis risk merits further investigation. (Multi-Ethnic Study of Atherosclerosis [MESA]; NCT00005487) [Copyright &y& Elsevier]

Background: Structural differences between the brains of people with schizophrenia and control subjects are highly replicated but the timing and clinical correlates are unclear. In the Edinburgh High Risk Study, we have followed up 162 individuals at high genetic risk of schizophrenia and 36 healthy control subjects over 10 years. Methods: Participants received detailed clinical and up to five structural magnetic resonance imaging (MRI) assessments at 2-year intervals. All 436 MRI scans acquired were parcellated and adjusted for between-scanner differences. The trajectory of any structural MRI changes was then investigated using mixed effects analysis of variance. Results: Seventeen of the 146 high-risk subjects who were scanned developed schizophrenia over the 8 years of the study. People at high genetic risk of schizophrenia had significantly greater reductions over time than the control group for whole brain volume and left and right prefrontal and temporal lobes. Greater prefrontal reductions were shown in high-risk subjects who subsequently became unwell compared with those who did not. These changes were significantly associated with increasing severity of psychotic symptoms. Conclusions: Individuals at high genetic risk of schizophrenia exhibited reductions in cerebral volume that were not found in control subjects. Changes in brain structure were also associated with increasing psychotic symptom severity as people developed schizophrenia. The progressive reductions found in those who went on to develop schizophrenia suggest an additional brain insult near to the time of onset. [Copyright &y& Elsevier]

MAPK phosphatase-1 (DUSP1/MKP-1) is a mitogen and stress-inducible dual specificity protein phosphatase, which can inactivate all three major classes of MAPK in mammalian cells. DUSPl/MKP-1 is implicated in cellular protection against variety of genotoxic insults including hydrogen peroxide, ionizing radiation, and cisplatin, but its role in the interplay between different MAPK pathways in determining cell death and survival is not fully understood. We have used pharmacological genetic tools to demonstrate that DUSP1/MKP-1 is an essential non-redundant regulator of UV-induced cell death in mouse embryo fibroblasts (MEFs). The induction of DUSP1/MKP-mRNA and protein in response to UV radiation is mediated activation of the p38a but not the INK1 or INK2 MAPK pathways. Furthermore, we identify MSK1 and -2 and their downstream effectors cAMP-response element-binding protein/ATF1 as mediators of UV-induced p38a-dependent DUSP1/MKP-1 transcription. Dusp1/Mkp-1 null MEFs display increased signaling through both the p38a and INK MAPK pathways and are acutely sensitive to UV-induced apoptosis. This lethality is rescued by the reintroduction of wild-type DUSP1/MKP-1 and by a mutant of DUSP1/MKP-1, which unable to bind to either p38a or ERK1/2, but retains full activity toward INK. Importantly, whereas small interfering RNA-mediated knockdown of DUSP1/MKP-1 sensitizes wild-type MEFs UV radiation, DUSP1/MKP-1 knockdown in MEFS lacking INK1 and -2 does not result in increased cell death. Our results demonstrate that cross-talk between the p38a and INK pathways mediated by induction of DUSP1/MKP-1 regulates the cellular response to UV radiation. [ABSTRACT FROM AUTHOR]

Aortic valve calcium (AVC) is common among older adults and shares epidemiologic and histopathologic similarities to atherosclerosis. However, prospective studies have failed to identify meaningful risk associations with incident (“new”) AVC or its progression. In the present study, AVC was quantified from serial computed tomographic images from 5,880 participants (aged 45 to 84 years) in the Multi-Ethnic Study of Atherosclerosis, using the Agatston method. Multivariate backward selection modeling was used to identify the risk factors for incident AVC and AVC progression. During a mean follow-up of 2.4 ± 0.9 years, 210 subjects (4.1%) developed incident AVC. The incidence rate (mean 1.7%/year) increased significantly with age (p <0.001). The risk factors for incident AVC included age, male gender, body mass index, current smoking, and the use of lipid-lowering and antihypertensive medications. Among those with AVC at baseline, the median rate of AVC progression was 2 Agatston units/year (interquartile range −21 to 37). The baseline Agatston score was a strong, independent predictor of progression, especially among those with high calcium scores at baseline. In conclusion, in this ethnically diverse, preclinical cohort, the rate of incident AVC increased significantly with age. The incident AVC risk was associated with several traditional cardiovascular risk factors, specifically age, male gender, body mass index, current smoking, and the use of both antihypertensive and lipid-lowering medications. AVC progression risk was associated with male gender and the baseline Agatston score. Additional research is needed to determine whether age- and stage-specific mechanisms underlie the risk of AVC progression. [Copyright &y& Elsevier]

Abstract: Effective intervention following self-harm is vital because of the strong link between self-harm and suicide. Unfortunately, services for people who self-harm have been poor in the UK and elsewhere. In 2004, the National Institute for Health and Clinical Excellence issued a guideline setting out clear standards for care following self-harm, many of which are included in this article. Whether this guideline has led to much needed improvements in care is not clear; there are few published experiences concerning implementation of the guidance but some studies suggest that care continues to be unsatisfactory. The barriers to implementation of self-harm guidelines are not clear, but the lack of definitive research evidence for effective treatments is a potential candidate. Several systematic reviews have failed to demonstrate a statistically significant reduction in fatal or non-fatal repetition following intervention after self-harm. Recent studies have, however, shown clear benefits for some psychological therapies – in particular for cognitive behavioural therapy with a problem-solving element. Promising results have also been demonstrated for some brief interventions designed to encourage uptake of aftercare following self-harm. This article sets out a little of the evidence for these potentially beneficial interventions, including recent developments in research evidence and implications for future research. [Copyright &y& Elsevier]

Objective: To characterize differences in disposition arrangement among rehab-eligible stroke patients at a Comprehensive Stroke Center before and during the COVID-19 pandemic.Materials and Methods: We retrospectively analyzed a prospective registry for demographics, hospital course, and discharge dispositions of rehab-eligible acute stroke survivors admitted 6 months prior to (10/2019-03/2020) and during (04/2020-09/2020) the COVID-19 pandemic. The primary outcome was discharge to an inpatient rehabilitation facility (IRF) as opposed to other facilities using descriptive statistics, and IRF versus home using unadjusted and adjusted backward stepwise logistic regression.Results: Of the 507 rehab-eligible stroke survivors, there was no difference in age, premorbid disability, or stroke severity between study periods (p>0.05). There was a 9% absolute decrease in discharges to an IRF during the pandemic (32.1% vs. 41.1%, p=0.04), which translated to 38% lower odds of being discharged to IRF versus home in unadjusted regression (OR 0.62, 95%CI 0.42-0.92, p=0.016). The lower odds of discharge to IRF persisted in the multivariable model (aOR 0.16, 95%CI 0.09-0.31, p<0.001) despite a significant increase in discharge disability (median discharge mRS 4 [IQR 2-4] vs. 2 [IQR 1-3], p<0.001) during the pandemic.Conclusions: Admission for stroke during the COVID-19 pandemic was associated with a significantly lower probability of being discharged to an IRF. This effect persisted despite adjustment for predictors of IRF disposition, including functional disability at discharge. Potential reasons for this disparity are explored. [ABSTRACT FROM AUTHOR]

Summary: Hearing loss is a common disorder in the paediatric community, with between 1 and 3 per 1000 live births being affected with severe-to-profound loss. Without early diagnosis, the sequelae of this condition can affect the child''s social and future professional development. Paediatricians may be the first clinicians to review and suspect hearing problems and therefore need a framework for further investigation and management. This article aims to give clinicians an overview of the management of hearing loss in children and to provide a logical approach to the detection, investigation and diagnosis of hearing impairment. The relevance of the early diagnosis cannot be overstated in order to negate and treat this disability, with its potential profound consequences. [Copyright &y& Elsevier]

Abstract: Type 2 diabetes is characterised by a gradual decline in insulin secretion in response to nutrient loads; hence, it is primarily a disorder of postprandial glucose (PPG) regulation. However, physicians continue to rely on fasting plasma glucose (FPG) and glycosylated haemoglobin (HbA1c) levels as indicators for disease management. There is a linear relationship between the risk of cardiovascular disease (CVD) and the two-hour oral glucose tolerance test (OGTT), while a recent study confirms postprandial hyperglycaemia as an independent risk factor for CVD in type 2 diabetes. At the same time, several intervention studies have shown that treating postprandial hyperglycaemia may reduce the incidence of new cardiovascular events. Evidence supports the hypothesis that postprandial hyperglycaemia may be linked to CVD through the generation of oxidative stress. Furthermore, clinical data suggest that postprandial hyperglycaemia is a common phenomenon, even in patients who may be considered in ‘good metabolic control’. Therefore, in addition to HbA1c and FPG, physicians should consider monitoring and targeting PPG in patients with type 2 diabetes. [Copyright &y& Elsevier]

Abstract: There are uneven standards of care for people who attend hospital because of self-harm (self-poisoning and self-injury), in the UK and elsewhere. In the hope of improving the situation the UK Department of Health commissioned a National Institute for Health and Clinical Excellence (NICE) Guideline on self-harm, which sets out the standards of care for staff in the emergency department. They should, in the first instance, evaluate the patient''s physical and mental health to allow for more thorough psychosocial assessment before the person leaves the hospital. The psychosocial assessment should take account of the person''s mental health and social needs, as well as their levels of perceived risk, and there should be adequate levels of training, supervision, privacy and inter-professional communication. Effective intervention following an episode of self-harm, whether initiated by emergency department staff of by mental health professionals, is an uncertain business because the evidence base is scant and equivocal. Research evidence fails to show clear advantage to simple alterations in the structure of the services such as the handing out of cards that offer the person a telephone number to call if he or she is feeling like undertaking further self-harm, or the sending of postcards that suggest getting in touch with the hospital. The best current evidence of benefit comes from brief forms of psychological therapy based on problem-solving techniques derived from interpersonal therapy of from cognitive therapy. Benefits include reduced repetition of self-harm and improvements in mood, hopelessness and problems experienced. [Copyright &y& Elsevier]

Summary: Runny nose is a common condition in childhood. The majority of cases are self-limiting and over-treatment should be avoided. However, very occasionally, rhinorrhoea is the presentation of serious disease. This article provides a practical classification and outlines principles of management. [Copyright &y& Elsevier]