This article reviews recent developments in tests of fundamental physics using atoms and molecules, including the subjects of parity violation, searches for permanent electric dipole moments, tests ...of the CPT theorem and Lorentz symmetry, searches for spatiotemporal variation of fundamental constants, tests of quantum electrodynamics, tests of general relativity and the equivalence principle, searches for dark matter, dark energy, and extra forces, and tests of the spin-statistics theorem. Key results are presented in the context of potential new physics and in the broader context of similar investigations in other fields. Ongoing and future experiments of the next decade are discussed.
Vitamin D and its metabolites have pleomorphic roles in both nervous system health and disease. Animal models have been paramount in contributing to our knowledge and understanding of the ...consequences of vitamin D deficiency on brain development and its implications for adult psychiatric and neurological diseases. The conflation of in vitro, ex vivo, and animal model data provide compelling evidence that vitamin D has a crucial role in proliferation, differentiation, neurotrophism, neuroprotection, neurotransmission, and neuroplasticity. Vitamin D exerts its biological function not only by influencing cellular processes directly, but also by influencing gene expression through vitamin D response elements. This review highlights the epidemiological, neuropathological, experimental and molecular genetic evidence implicating vitamin D as a candidate in influencing susceptibility to a number of psychiatric and neurological diseases. The strength of evidence varies for schizophrenia, autism, Parkinson's disease, amyotrophic lateral sclerosis, Alzheimer's disease, and is especially strong for multiple sclerosis.
In older children, one of the standards for indexing left ventricular mass (LVM) is height raised to an exponential power of 2.7. The purpose of this study was to establish a normal value for the ...pediatric age group and to determine how, if at all, LVM/height(2.7) varies in children.
M-mode echocardiography was performed in 2,273 nonobese, healthy children (1,267 boys, 1,006 girls; age range 0-18 years). Curves were constructed for the 5th, 10th, 25th, 50th, 75th, 90th, and 95th quantiles of LVM/height(2.7).
In children aged > 9 years, median LVM/height(2.7) ranged from 27 to 32 g/m(2.7) and had little variation with age. However, in those aged < 9 years, LVM/height(2.7) varied significantly, and percentiles for newborns and infants were approximately double the levels for older children and adolescents: the 95th percentile ranged from 80 g/m(2.7) for newborns to 40 g/m(2.7) for 11-year-olds.
For patients aged > 9 years, quantiles of LVM/height(2.7) vary little, and values > 40 g/m(2.7) in girls and > 45 g/m(2.7) in boys can be considered abnormal (ie, > 95th percentile). However, for patients aged < 9 years, the index varies with age, and therefore, measured LVM/height(2.7) must be compared with percentile curves, which are provided. This variation in LVM/height(2.7) in younger children indicates that a better indexing method is needed for this age group. Nevertheless, these data are valuable in that they provide normal values with which patient data can be compared.
Summary
Background
Rates of malignancies and hospitalized infectious events (HIEs) among psoriasis patients are higher than in the general population, but it is unclear if higher rates are associated ...with the underlying inflammatory state, treatments or both.
Objectives
To assess the incidence of malignancies and HIEs in a healthy US population, a psoriasis population, and four treated psoriasis populations.
Methods
Using a US claims database, we identified a general population, a psoriasis cohort, and four treatment cohorts non‐biologic systemics, etanercept, other TNF blockers (adalimumab, infliximab) and phototherapy to assess the incidence of lymphomas, nonmelanoma skin cancer (NMSC), all malignancies (excluding NMSC), and HIEs, standardized for age and sex.
Results
Among 40 987 patients with psoriasis, 11% were prescribed non‐biologics, 15% etanercept, 6% other TNF blockers and 11% phototherapy. For all cancers, the psoriasis population rate (114/10 000 person‐years) was 20% greater than the rate found in the general population (95/10 000 person‐years). For NMSC, the psoriasis population rate (129/10 000 person‐years) was 65% greater than the general population rate (78/10 000 person‐years). The incidence rate for each treatment modality was lower than the overall psoriasis cohort, except for phototherapy. There was little difference in the rates of lymphomas. NMSC rates were higher among patients treated with phototherapy. HIE rates ranged from 165/10 000 person‐years for the phototherapy group to 262/10 000 person‐years for the other anti‐TNF group.
Conclusions
Patients with psoriasis appear to have higher rates of malignancy and HIE than the general population, with little difference in rates between the treatment methods, except for a higher rate of cancer among those receiving phototherapy.
What's already known about this topic?
Some evidence shows elevated rates of malignancies and serious infections among psoriasis patients in general but also for those on therapeutic regimens.
What does this study add?
This study provides evidence that the elevated rates of malignancy and serious infections found in psoriasis patients may be due to biological reasons other than specific treatment modalities.
Summary
Background
A validated tool for the dynamic severity assessment of hidradenitis suppurativa/acne inversa (HS) is lacking.
Objectives
To develop and validate a novel dynamic scoring system to ...assess the severity of HS.
Methods
A Delphi voting procedure was conducted among the members of the European Hidradenitis Suppurativa Foundation (EHSF) to achieve consensus towards an initial HS Severity Score System (HS4). Strengths and weaknesses of HS4 were examined by a multicentre prospective study. Multivariate logistic regression, discriminant analysis and receiver operating characteristic curves, as well as examination for correlation (Spearman's rho) and agreement (Cohen's kappa) with existing scores, were engaged to recognize the variables for a new International HS4 (IHS4) that was established by a second Delphi round.
Results
Consensus HS4 was based on number of skin lesions, number of skin areas involved and Dermatology Life Quality Index (DLQI), and was evaluated by a sample of 236 patients from 11 centres. Subsequently, a multivariate regression model calculated adjusted odds ratios for several clinical signs. Nodules, abscesses and draining tunnels resulted as the scoring variables. Three candidate scores were presented to the second Delphi round. The resulting IHS4 score is arrived at by the number of nodules (multiplied by 1) plus the number of abscesses (multiplied by 2) plus the number of draining tunnels (multiplied by 4). A total score of 3 or less signifies mild, 4–10 signifies moderate and 11 or higher signifies severe disease. Cohen's kappa was fair (κ = 0·32) compared with Hurley classification, and moderate (κ = 0·49) compared with Expert Opinion. Correlation was good (ρ > 0·6) with Hurley classification, Expert Opinion, Physician's Global Assessment and Modified Sartorius score, and moderate for DLQI (ρ = 0·36).
Conclusions
The novel IHS4 is a validated tool to dynamically assess HS severity and can be used both in real‐life and the clinical trials setting.
What's already known about this topic?
The modified Sartorius score, Hurley classification and Physician's Global Assessment have been used to assess severity of hidradenitis suppurativa.
However, these are often either difficult to use in daily clinical practice or static and generally poorly validated.
What does this study add?
The proposed score is a systematically constructed, validated and simple tool to assess disease severity, and can be adapted both to clinical research and daily practice.
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Background Comparing effectiveness of biologics in real-world settings will help inform treatment decisions. Objectives We sought to compare therapeutic responses among patients initiating ...infliximab, adalimumab, or etanercept versus ustekinumab during the Psoriasis Longitudinal Assessment and Registry (PSOLAR). Methods Proportions of patients achieving a Physician Global Assessment score of clear (0)/minimal (1) and mean decrease in percentage of body surface area with psoriasis were evaluated at 6 and 12 months. Adjusted logistic regression (Physician Global Assessment score 0/1) and analysis of covariance (percentage of body surface area with psoriasis) were performed to determine treatment factors associated with effectiveness. Results Of 2541 new users on registry, 2076 had efficacy data: ustekinumab (n = 1041), infliximab (n = 116), adalimumab (n = 662), and etanercept (n = 257). Patients receiving tumor necrosis factor-alpha(-α) inhibitors were significantly less likely to achieve Physician Global Assessment score 0/1 versus ustekinumab (infliximab odds ratio {OR} 0.396, P < .0001, adalimumab OR 0.686, P = .0012, etanercept OR 0.554, P = .0003 at 6 months and infliximab OR 0.449, P = .0040 at 12 months). Mean decrease in percentage of body surface area with psoriasis was significantly greater for ustekinumab versus adalimumab (point estimate 1.833, P = .0020) and etanercept (point estimate 3.419, P < .0001) at 6 months and versus infliximab (point estimate 3.945, P = .0005) and etanercept (point estimate 2.778, P = .0007) at 12 months. Limitations Treatment selection bias and limited data for doing adjustments are limitations. Conclusions In PSOLAR, effectiveness of ustekinumab was significantly better versus all 3 tumor necrosis factor-α inhibitors studied for the majority of comparisons at 6 and 12 months.
Abstract Objectives The aim of this study was to identify a unifying cardiac pathophysiology that explains the cardiac pathological features in sickle cell disease (SCD). Background Cardiopulmonary ...complications, the leading cause of adult death in SCD, are associated with heart chamber dilation, diastolic dysfunction, elevated tricuspid regurgitant jet velocity (TRV), and pulmonary hypertension. However, no unifying cardiac pathophysiology has been identified to explain these findings. Methods In a 2-part study, we first examined patients with SCD who underwent screening echocardiography during steady state at our institution. We then conducted a meta-analysis of cardiac studies in SCD. Results In the 134 patients with SCD studied (median age 11 years), significant enlargement of the left atrial volume was present ( z -score 3.1, p = 0.002), shortening fraction was normal (37.6 ± 4.7%), and lateral and septal ratios of mitral velocity to early diastolic velocity of the mitral annulus (E/e′) were severely abnormal in 8% and 14% of patients, respectively, indicating impaired diastolic function. Both TRV and lateral E/e′ correlated with enlarged left atrial volume in SCD (p = 0.003 and p = 0.006, respectively). Meta-analysis of 68 studies confirmed significant left atrial diameter enlargement in patients with SCD compared with controls, evidence of diastolic dysfunction and enlarged left ventricular end-diastolic dimension with normal shortening fraction. The majority of patients with catheter-confirmed pulmonary hypertension had mild pulmonary venous hypertension consistent with restrictive cardiac physiology. Conclusions Patients with SCD have a unique form of cardiomyopathy with restrictive physiology that is superimposed on hyperdynamic physiology and is characterized by diastolic dysfunction, left atrial dilation, and normal systolic function. This combination results in mild, secondary, pulmonary venous hypertension and elevated TRV. Sudden death is common in other forms of restrictive cardiomyopathy. Our finding of this unique restrictive cardiomyopathy may explain the increased mortality rates and sudden death seen in patients with SCD with mildly elevated TRV.
Reversibility of Cardiac Abnormalities in Morbidly Obese Adolescents Holly M. Ippisch, Thomas H. Inge, Stephen R. Daniels, Baiyang Wang, Philip R. Khoury, Sandra A. Witt, Betty J. Glascock, Victor F. ...Garcia, Thomas R. Kimball Cardiac abnormalities are present in morbidly obese adolescents; it is unclear whether these reverse with weight loss. Thirty-eight adolescents were evaluated with echocardiography before and after bariatric surgery. After weight loss, left ventricular mass (LVM) index decreased and left ventricular geometry, prevalence of concentric left ventricular hypertrophy (LVH), diastolic function, and cardiac workload improved. Elevated LVM index, concentric LVH, diastolic function, and cardiac workload improve after surgically induced weight loss in morbidly obese adolescents. Large weight loss owing to bariatric surgery improves predictors of future cardiovascular morbidity in these young people.
Supplementation by the general public with vitamin D at doses above the Tolerable Upper Level of Intake (UL) is becoming quite common. The objective of the current analysis was to characterize the ...effect of vitamin D supplementation at doses up to 15,000 IU/d in a community-based program on vitamin D status, calcium homeostasis as well as on kidney, liver and immune function. We evaluated data collected for 3,882 participants in a community program for whom there were blood measurements at program entry and at follow-up within 6-18 months between 2013 and 2015. Participants were supplemented with a wide range of vitamin D doses (1,000 - 15,000 IU/d) aimed at achieving serum 25-hydroxyvitamin D 25(OH)D levels of at least 100 nmol/L. Serum 25(OH)D concentrations up to 300 nmol/L were achieved without perturbation of calcium homeostasis or incidence of toxicity. Hypercalcemia and hypercalciuria were not related to an increase in 25(OH)D concentrations nor vitamin D dose. To achieve serum 25(OH)D levels >100 nmol/L on average, required vitamin D intakes of 6,000 IU/d for normal Body Mass Index (BMI), 7,000 IU/d for overweight and 8,000 IU/d for obese. Doses of vitamin D in excess of 6,000 IU/d were required to achieve serum 25(OH)D concentrations above 100 nmol/L, especially in individuals who were overweight or obese without any evidence of toxicity. Serum 25(OH)D concentrations up to 300 nmol/L were found to be safe.
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