Calculation of the Electron Self Energy for Low Nuclear Charge

We present a nonperturbative numerical evaluation of the one-photon electron self energy for hydrogenlike ions with low nuclear charge numbers Z=1 to 5. Our calculation for the 1S state has a numerical uncertainty of 0.8 Hz for hydrogen and 13 Hz for singly-ionized helium. Resummation and convergence acceleration techniques that reduce the computer time by about three orders of magnitude were employed in the calculation. The numerical results are compared to results based on known terms in the expansion of the self energy in powers of (Z alpha).Comment: 10 pages, RevTeX, 2 figure

Electron Self Energy for the K and L Shell at Low Nuclear Charge

A nonperturbative numerical evaluation of the one-photon electron self energy for the K- and L-shell states of hydrogenlike ions with nuclear charge numbers Z=1 to 5 is described. Our calculation for the 1S state has a numerical uncertainty of 0.8 Hz in atomic hydrogen, and for the L-shell states (2S and 2P) the numerical uncertainty is 1.0 Hz. The method of evaluation for the ground state and for the excited states is described in detail. The numerical results are compared to results based on known terms in the expansion of the self energy in powers of (Z alpha).Comment: 21 pages, RevTeX, 5 Tables, 6 figure

Children with severe acute asthma admitted to Dutch PICUs:A changing landscape

The number of children requiring pediatric intensive care unit (PICU) admission for severe acute asthma (SAA) around the world has increased. OBJECTIVES: We investigated whether this trend in SAA PICU admissions is present in the Netherlands. METHODS: A multicenter retrospective cohort study across all tertiary care PICUs in the Netherlands. Inclusion criteria were children (2-18 years) hospitalized for SAA between 2003 and 2013. Data included demographic data, asthma diagnosis, treatment, and mortality. RESULTS: In the 11-year study period 590 children (660 admissions) were admitted to a PICU with a threefold increase in the number of admissions per year over time. The severity of SAA seemed unchanged, based on the first blood gas, length of stay and mortality rate (0.6%). More children received highflow nasal cannula (P < 0.001) and fewer children needed invasive ventilation (P < 0.001). In 58% of the patients the maximal intravenous (IV) salbutamol infusion rate during PICU admission was 1 mcg/kg/min. However, the number of patients treated with IV salbutamol in the referring hospitals increased significantly over time (P = 0.005). The proportion of steroid-naïve patients increased from 35% to 54% (P = 0.004), with a significant increase in both age groups (2-4 years [P = 0.026] and 5-17 years [P = 0.036]). CONCLUSIONS: The number of children requiring PICU admission for SAA in the Netherlands has increased. We speculate that this threefold increase is explained by an increasing number of steroid-naïve children, in conjunction with a lowered threshold for PICU admission, possibly caused by earlier use of salbutamol IV in the referring hospitals

Effects of the fungicide metiram in outdoor freshwater microcosms: responses of invertebrates, primary producers and microbes

The ecological impact of the dithiocarbamate fungicide metiram was studied in outdoor freshwater microcosms, consisting of 14 enclosures placed in an experimental ditch. The microcosms were treated three times (interval 7 days) with the formulated product BAS 222 28F (Polyram®). Intended metiram concentrations in the overlying water were 0, 4, 12, 36, 108 and 324 μg a.i./L. Responses of zooplankton, macroinvertebrates, phytoplankton, macrophytes, microbes and community metabolism endpoints were investigated. Dissipation half-life (DT50) of metiram was approximately 1–6 h in the water column of the microcosm test system and the metabolites formed were not persistent. Multivariate analysis indicated treatment-related effects on the zooplankton (NOECcommunity = 36 μg a.i./L). Consistent treatment-related effects on the phytoplankton and macroinvertebrate communities and on the sediment microbial community could not be demonstrated or were minor. There was no evidence that metiram affected the biomass, abundance or functioning of aquatic hyphomycetes on decomposing alder leaves. The most sensitive populations in the microcosms comprised representatives of Rotifera with a NOEC of 12 μg a.i./L on isolated sampling days and a NOEC of 36 μg a.i./L on consecutive samplings. At the highest treatment-level populations of Copepoda (zooplankton) and the blue-green alga Anabaena (phytoplankton) also showed a short-term decline on consecutive sampling days (NOEC = 108 μg a.i./L). Indirect effects in the form of short-term increases in the abundance of a few macroinvertebrate and several phytoplankton taxa were also observed. The overall community and population level no-observed-effect concentration (NOECmicrocosm) was 12–36 μg a.i./L. At higher treatment levels, including the test systems that received the highest dose, ecological recovery of affected measurement endpoints was fast (effect period < 8 weeks)

Defective Membrane Remodeling in Neuromuscular Diseases: Insights from Animal Models

Proteins involved in membrane remodeling play an essential role in a plethora of cell functions including endocytosis and intracellular transport. Defects in several of them lead to human diseases. Myotubularins, amphiphysins, and dynamins are all proteins implicated in membrane trafficking and/or remodeling. Mutations in myotubularin, amphiphysin 2 (BIN1), and dynamin 2 lead to different forms of centronuclear myopathy, while mutations in myotubularin-related proteins cause Charcot-Marie-Tooth neuropathies. In addition to centronuclear myopathy, dynamin 2 is also mutated in a dominant form of Charcot-Marie-Tooth neuropathy. While several proteins from these different families are implicated in similar diseases, mutations in close homologues or in the same protein in the case of dynamin 2 lead to diseases affecting different tissues. This suggests (1) a common molecular pathway underlying these different neuromuscular diseases, and (2) tissue-specific regulation of these proteins. This review discusses the pathophysiology of the related neuromuscular diseases on the basis of animal models developed for proteins of the myotubularin, amphiphysin, and dynamin families. A better understanding of the common mechanisms between these neuromuscular disorders will lead to more specific health care and therapeutic approaches

Collaborative care for patients with bipolar disorder: a randomised controlled trial

<p>Abstract</p> <p>Background</p> <p>Bipolar disorder is a severe mental illness with serious consequences for daily living of patients and their caregivers. Care as usual primarily consists of pharmacotherapy and supportive treatment. However, a substantial number of patients show a suboptimal response to treatment and still suffer from frequent episodes, persistent interepisodic symptoms and poor social functioning. Both psychiatric and somatic comorbid disorders are frequent, especially personality disorders, substance abuse, cardiovascular diseases and diabetes. Multidisciplinary collaboration of professionals is needed to combine all expertise in order to achieve high-quality integrated treatment. 'Collaborative Care' is a treatment method that could meet these needs. Several studies have shown promising effects of these integrated treatment programs for patients with bipolar disorder. In this article we describe a research protocol concerning a study on the effects of Collaborative Care for patients with bipolar disorder in the Netherlands.</p> <p>Methods/design</p> <p>The study concerns a two-armed cluster randomised clinical trial to evaluate the effectiveness of Collaborative Care (CC) in comparison with Care as usual (CAU) in outpatient clinics for bipolar disorder or mood disorders in general. Collaborative Care includes individually tailored interventions, aimed at personal goals set by the patient. The patient, his caregiver, the nurse and the psychiatrist all are part of the Collaborative Care team. Elements of the program are: contracting and shared decision making; psycho education; problem solving treatment; systematic relapse prevention; monitoring of outcomes and pharmacotherapy. Nurses coordinate the program. Nurses and psychiatrists in the intervention group will be trained in the intervention. The effects will be measured at baseline, 6 months and 12 months. Primary outcomes are psychosocial functioning, psychiatric symptoms, and quality of life. Caregiver outcomes are burden and satisfaction with care.</p> <p>Discussion</p> <p>Several ways to enhance the quality of this study are described, as well as some limitations caused by the complexities of naturalistic treatment settings where not all influencing factors on an intervention and the outcomes can be controlled.</p> <p>Trial Registration</p> <p>The Netherlands Trial Registry, <a href="http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=2600">NTR2600</a>.</p

Pathogenesis of adolescent idiopathic scoliosis in girls - a double neuro-osseous theory involving disharmony between two nervous systems, somatic and autonomic expressed in the spine and trunk: possible dependency on sympathetic nervous system and hormones with implications for medical therapy

Anthropometric data from three groups of adolescent girls - preoperative adolescent idiopathic scoliosis (AIS), screened for scoliosis and normals were analysed by comparing skeletal data between higher and lower body mass index subsets. Unexpected findings for each of skeletal maturation, asymmetries and overgrowth are not explained by prevailing theories of AIS pathogenesis. A speculative pathogenetic theory for girls is formulated after surveying evidence including: (1) the thoracospinal concept for right thoracic AIS in girls; (2) the new neuroskeletal biology relating the sympathetic nervous system to bone formation/resorption and bone growth; (3) white adipose tissue storing triglycerides and the adiposity hormone leptin which functions as satiety hormone and sentinel of energy balance to the hypothalamus for long-term adiposity; and (4) central leptin resistance in obesity and possibly in healthy females. The new theory states that AIS in girls results from developmental disharmony expressed in spine and trunk between autonomic and somatic nervous systems. The autonomic component of this double neuro-osseous theory for AIS pathogenesis in girls involves selectively increased sensitivity of the hypothalamus to circulating leptin (genetically-determined up-regulation possibly involving inhibitory or sensitizing intracellular molecules, such as SOC3, PTP-1B and SH2B1 respectively), with asymmetry as an adverse response (hormesis); this asymmetry is routed bilaterally via the sympathetic nervous system to the growing axial skeleton where it may initiate the scoliosis deformity (leptin-hypothalamic-sympathetic nervous system concept = LHS concept). In some younger preoperative AIS girls, the hypothalamic up-regulation to circulating leptin also involves the somatotropic (growth hormone/IGF) axis which exaggerates the sympathetically-induced asymmetric skeletal effects and contributes to curve progression, a concept with therapeutic implications. In the somatic nervous system, dysfunction of a postural mechanism involving the CNS body schema fails to control, or may induce, the spinal deformity of AIS in girls (escalator concept). Biomechanical factors affecting ribs and/or vertebrae and spinal cord during growth may localize AIS to the thoracic spine and contribute to sagittal spinal shape alterations. The developmental disharmony in spine and trunk is compounded by any osteopenia, biomechanical spinal growth modulation, disc degeneration and platelet calmodulin dysfunction. Methods for testing the theory are outlined. Implications are discussed for neuroendocrine dysfunctions, osteopontin, sympathoactivation, medical therapy, Rett and Prader-Willi syndromes, infantile idiopathic scoliosis, and human evolution. AIS pathogenesis in girls is predicated on two putative normal mechanisms involved in trunk growth, each acquired in evolution and unique to humans

[DRESS syndrome as a result of sulfasalazine use].

A 24-year-old female developed DRESS syndrome (Drug Reaction with Eosinophilia and Systemic Symptoms) as a result of sulfasalazine use. The DRESS syndrome is a severe and acute hypersensitivity reaction that can be caused by a variety of drugs. The clinical presentation is diverse; the most common symptoms are fever, exanthema and lymphadenopathy. Haematologic abnormalities such as leukocytosis, accompanied primarily with eosinophilia, and sometimes atypical lymphocytes are also frequently reported. In most cases the DRESS syndrome needs no further treatment after discontinuation of the associated drug. However, 20% of patients are severely affected and the DRESS syndrome is potentially life-threatening. The patient was successfully treated with a glucocorticoid and an antihistamine

A biocompatible reverse thermoresponsive polymer for ocular drug delivery

Age-related macular degeneration (AMD) is a leading cause of vision loss, the treatment of which may require monthly intravitreal injections. This is a burden on patients and health services, and new delivery modalities that reduce injection frequency are required. To that end, we investigated the suitability of a novel reverse thermoresponsive polymer (RTP) as an ocular drug-delivery vehicle. In this work, we detail the structure and synthesis of a novel RTP, and determine drug release curves for two drugs commonly used in the treatment of AMD, bevacizumab and aflibercept. Biocompatibility of the RTP was assessed in vitro in human and rat cell lines and in vivo following intravitreal injection in rats. Bevacizumab demonstrated a more appropriate release profile than aflibercept, with 67% released within 14 days and 78% released in total over a 183-day period. No toxic effects of RTP were seen in human or rat cells in up to 14 days of co-culture with RTP. Following intravitreal injection, intraocular pressure was unaffected by the presence of RTP and no changes in retinal function or structure were observed at 1 week or 1 month post-injection. RTP injection did not cause inflammation, gliosis or apoptosis in the retina. This work demonstrates the potential suitability of the novel RTP as a sustained-release vehicle for ocular drug delivery for anti-neovascular therapies. Optimization of polymer chemistry for optimal drug loading and release is needed