Mixture of Kernels and Iterated Semidirect Product of Diffeomorphisms Groups

In the framework of large deformation diffeomorphic metric mapping (LDDMM), we develop a multi-scale theory for the diffeomorphism group based on previous works. The purpose of the paper is (1) to develop in details a variational approach for multi-scale analysis of diffeomorphisms, (2) to generalise to several scales the semidirect product representation and (3) to illustrate the resulting diffeomorphic decomposition on synthetic and real images. We also show that the approaches presented in other papers and the mixture of kernels are equivalent.Comment: 21 pages, revised version without section on evaluatio

Theoretical determination of the nonlinear optical properties of inorganic polymers

Third order hyperpolarizabilities were calculated using the Huckel Hamiltonian and third order perturbation theory for a series of phosphonitrilic compounds, (X{sub 2}P-N){sub n}, as a function of bond length alternation, ligand substitution and backbone conformation. Phosphonitrilic compounds show hyperpolarizabilities comparable to those reported for organic species, and are modulated by ligand group electronegativity. In contrast to organic polyenes, the difference in {pi} orbital energy between phosphorus and nitrogen is critical to determining the onset of saturation and the magnitude of the hyperpolarizability. Conformation effects are smaller than those seen in polyenes. 15 refs., 5 figs

Evaluation of early and late presentation of patients with ocular mucous membrane pemphigoid to two major tertiary referral hospitals in the United Kingdom

PURPOSE: Ocular mucous membrane pemphigoid (OcMMP) is a sight-threatening autoimmune disease in which referral to specialists units for further management is a common practise. This study aims to describe referral patterns, disease phenotype and management strategies in patients who present with either early or established disease to two large tertiary care hospitals in the United Kingdom.\ud \ud PATIENTS AND METHODS: In all, 54 consecutive patients with a documented history of OcMMP were followed for 24 months. Two groups were defined: (i) early-onset disease (EOD:<3 years, n=26, 51 eyes) and (ii) established disease (EstD:>5 years, n=24, 48 eyes). Data were captured at first clinic visit, and at 12 and 24 months follow-up. Information regarding duration, activity and stage of disease, visual acuity (VA), therapeutic strategies and clinical outcome were analysed.\ud \ud RESULTS: Patients with EOD were younger and had more severe conjunctival inflammation (76% of inflamed eyes) than the EstD group, who had poorer VA (26.7%=VA<3/60, P<0.01) and more advanced disease. Although 40% of patients were on existing immunosuppression, 48% required initiation or switch to more potent immunotherapy. In all, 28% (14) were referred back to the originating hospitals for continued care. Although inflammation had resolved in 78% (60/77) at 12 months, persistence of inflammation and progression did not differ between the two phenotypes. Importantly, 42% demonstrated disease progression in the absence of clinically detectable inflammation.\ud \ud CONCLUSIONS: These data highlight that irrespective of OcMMP phenotype, initiation or escalation of potent immunosuppression is required at tertiary hospitals. Moreover, the conjunctival scarring progresses even when the eye remains clinically quiescent. Early referral to tertiary centres is recommended to optimise immunosuppression and limit long-term ocular damage.\ud \u

Exclusive Measurements of pd→3Heππpd\to ^3He \pi\pi : the ABCABC Effect Revisited

Exclusive measurements of the reactions $pd\to$ $^3He \pi^+ \pi^-$ and $pd\to$ $^3He \pi^0\pi^0$ have been carried out at $T_p=0.895$ GeV at the CELSIUS storage ring using the WASA detector. The $\pi^+\pi^-$ channel evidences a pronounced enhancement at low invariant $\pi\pi$ masses - as anticipated from previous inclusive measurements of the ABC effect. This enhancement is seen to be even much larger in the isoscalar $\pi^0\pi^0$ channel. The differential distributions prove this enhancement to be of scalar-isoscalar nature. $\Delta\Delta$ calculations give a good description of the data, if a boundstate condition is imposed for the intermediate $\Delta\Delta$ system.Comment: extended version, 8 pages, 7 figures, theoretical model calculations adde

A prospective open-label treatment trial of olanzapine monotherapy in children and adolescents with bipolar disorder

OBJECTIVE: The goal of this study was to assess the effectiveness and tolerability of olanzapine in the treatment of acute mania in children and adolescents. METHODS: This was an 8-week, open-label, prospective study of olanzapine monotherapy (dose range 2.5-20 mg/day) involving 23 bipolar youths (manic, mixed, or hypomanic; 5-14 years old). Weekly assessments were made using the Young Mania Rating Scale (YMRS), Clinical Global Impressions Severity Scale (CGI-S), Brief Psychiatric Rating Scale, and Children\u27s Depression Rating Scale. Adverse events were assessed through self-reports, vital sign and weight monitoring, laboratory analytes, and extrapyramidal symptom rating scales (Barnes Akathisia Scale, Simpson-Angus Scale, and Abnormal Involuntary Movement Scale). RESULTS: Twenty-two of the 23 youths (96%) completed the study. Olanzapine treatment was associated with significant improvement in mean YMRS score (-19.0 +/- 9.2, p \u3c 0.001). Using predefined criteria for improvement of \u3e or = 30% decline in the YMRS and a CGI-S Mania score of \u3c or = 3 at endpoint, the overall response rate was 61%. Overall, olanzapine was well tolerated, and extrapyramidal symptom measures were not significantly different from baseline. Body weight increased significantly over the study (5.0 +/- 2.3 kg, p \u3c 0.001). CONCLUSIONS: Open-label olanzapine treatment was efficacious and well tolerated in the treatment of acute mania in youths with bipolar disorder. Future placebo-controlled, double-blind studies are warranted

Substance abuse and psychiatric co-morbidity as predictors of premature mortality in Swedish drug abusers a prospective longitudinal study 1970 - 2006

<p>Abstract</p> <p>Background</p> <p>Few longitudinal cohort studies have focused on the impact of substances abused and psychiatric disorders on premature mortality. The aim of the present study was to identify predictors of increased risk of drug related death and non drug related death in substance abusers of opiates, stimulants, cannabis, sedatives/hypnotics, hallucinogens and alcohol over several decades.</p> <p>Methods</p> <p>Follow-up study of a consecutive cohort of 561 substance abusers, admitted to a detoxification unit January 1970 to February 1978 in southern Sweden, and followed up in 2006. Demographic and clinical data, substance diagnoses and three groups of psychiatric diagnoses were identified at first admission. Causes of death were coded according to ICD-10 and classified as drug related deaths or non drug related deaths. To identify the incidence of some probable risk factors of drug related premature death, the data were subjected to a competing risks Cox regression analysis.</p> <p>Results</p> <p>Of 561 patients in the cohort, 11 individuals had either emigrated or could not be located, and 204/561 patients (36.4%) were deceased by 2006. The cumulative risk of drug related death increased more in the first 15 years and leveled out later on when non drug related causes of death had a similar incidence. In the final model, male gender, regular use of opiates or barbiturates at first admission, and neurosis were associated with an increased risk of drug related premature death, while cannabis use and psychosis were associated with a decreased risk. Neurosis, mainly depression and/or anxiety disorders, predicted drug related premature death while chronic psychosis and personality disorders did not. Chronic alcohol addiction was associated with increased risk of non drug related death.</p> <p>Conclusions</p> <p>The cohort of drug abusers had an increased risk of premature death to the age of 69. Drug related premature death was predicted by male gender, the use of opiates or barbiturates and depression and anxiety disorders at first admission. The predicted cumulative incidence of drug related death was significantly higher in opiate and barbiturate abusers over the observed period of 37 years, while stimulant abuse did not have any impact. Alcohol contributed to non drug related death.</p

Effectiveness of Chêneau brace treatment for idiopathic scoliosis: prospective study in 79 patients followed to skeletal maturity

<p>Abstract</p> <p>Background</p> <p>Progressive idiopathic scoliosis can negatively influence the development and functioning of 2-3% of adolescents, with health consequences and economic costs, placing the disease in the centre of interest of the developmental medicine. The aim of this study was to evaluate the effectiveness of Chêneau brace in the management of idiopathic scoliosis.</p> <p>Methods</p> <p>A prospective observational study according to SOSORT and SRS recommendations comprised 79 patients (58 girls and 21 boys) with progressive idiopathic scoliosis, treated with Chêneau brace and physiotherapy, with initial Cobb angle between 20 and 45 degrees, no previous brace treatment, Risser 4 or more at the final evaluation and minimum one year follow-up after weaning the brace. Achieving 50° of Cobb angle was considered surgical recommendation.</p> <p>Results</p> <p>At follow-up 20 patients (25.3%) improved, 18 patients (22.8%) were stable, 31 patients (39.2%) progressed below 50 degrees and 10 patients (12.7%) progressed beyond 50 degrees (2 of these 10 patients progressed beyond 60 degrees). Progression concerned the younger and less skeletally mature patients.</p> <p>Conclusion</p> <p>Conservative treatment with Chêneau orthosis and physiotherapy was effective in halting scoliosis progression in 48.1% of patients. The results of this study suggest that bracing is effective in reducing the incidence of surgery in comparison with natural history.</p

The composite first person narrative: Texture, structure, and meaning in writing phenomenological descriptions

This paper illustrates the use of composite first person narrative interpretive methods, as described by Todres, across a range of phenomena. This methodology introduces texture into the presently understood structures of phenomena and thereby creates new understandings of the phenomenon, bringing about a form of understanding that is relationally alive that contributes to improved caring practices. The method is influenced by the work of Gendlin, Heidegger, van Manen, Gadamer, and Merleau-Ponty. The method's applicability to different research topics is demonstrated through the composite narratives of nursing students learning nursing practice in an accelerated and condensed program, obese female adolescents attempting weight control, chronically ill male parolees, and midlife women experiencing distress during menopause. Within current research, these four phenomena have been predominantly described and understood through quantified articulations that give the reader a structural understanding of the phenomena, but the more embodied or “contextual” human qualities of the phenomena are often not visible. The “what is it like” or the “unsaid” aspects of such human phenomena are not clear to the reader when proxies are used to “account for” a variety of situated conditions. This novel method is employed to re-present narrative data and findings from research through first person accounts that blend the voices of the participants with those of the researcher, emphasizing the connectedness, the “we” among all participants, researchers, and listeners. These re-presentations allow readers to develop more embodied understandings of both the texture and structure of each of the phenomena and illustrate the use of the composite account as a way for researchers to better understand and convey the wholeness of the experience of any phenomenon under inquiry

Characterization of the role of BGS13 in the secretory mechanism of Pichia pastoris

The methylotrophic yeast Pichia pastoris has been utilized for heterologous protein expression for over 30 years. Because P. pastoris secretes few of its own proteins, the exported recombinant protein is the major polypeptide in the extracellular medium, making purification relatively easy. Unfortunately, some recombinant proteins intended for secretion are retained within the cell. A mutant strain isolated in our laboratory, containing a disruption of the BGS13 gene, displayed elevated levels of secretion for a variety of reporter proteins. The Bgs13 peptide (Bgs13p) is similar to the Saccharomyces cerevisiae protein kinase C 1 protein (Pkc1p), but its specific mode of action is currently unclear. To illuminate differences in the secretion mechanism between the wild-type (wt) strain and the bgs13 strain, we determined that the disrupted bgs13 gene expressed a truncated protein that had reduced protein kinase C activity and a different location in the cell, compared to the wt protein. Because the Pkc1p of baker’s yeast plays a significant role in cell wall integrity, we investigated the sensitivity of the mutant strain’s cell wall to growth antagonists and extraction by dithiothreitol, determining that the bgs13 strain cell wall suffered from inherent structural problems although its porosity was normal. A proteomic investigation of the bgs13 strain secretome and cell wall-extracted peptides demonstrated that, compared to its wt parent, the bgs13 strain also displayed increased release of an array of normally secreted, endogenous proteins, as well as endoplasmic reticulum-resident chaperone proteins, suggesting that Bgs13p helps regulate the unfolded protein response and protein sorting on a global scale. IMPORTANCE The yeast Pichia pastoris is used as a host system for the expression of recombinant proteins. Many of these products, including antibodies, vaccine antigens, and therapeutic proteins such as insulin, are currently on the market or in late stages of development. However, one major weakness is that sometimes these proteins are not secreted from the yeast cell efficiently, which impedes and raises the cost of purification of these vital proteins. Our laboratory has isolated a mutant strain of Pichia pastoris that shows enhanced secretion of many proteins. The mutant produces a modified version of Bgs13p. Our goal is to understand how the change in the Bgs13p function leads to improved secretion. Once the Bgs13p mechanism is illuminated, we should be able to apply this understanding to engineer new P. pastoris strains that efficiently produce and secrete life-saving recombinant proteins, providing medical and economic benefits