38 research outputs found
Epidemiology and health related quality of life in hypoparathyroidism in Norway.
OBJECTIVE: The epidemiology of hypoparathyroidism (HP) is largely unknown. We aimed to determine prevalence, etiologies, health related quality of life (HRQoL) and treatment pattern of HP. METHODS: Patients with HP and 22q11 deletion syndrome (DiGeorge syndrome) were identified in electronic hospital registries. All identified patients were invited to participate in a survey. Among patients who responded, HRQoL was determined by Short Form 36 (SF-36) and Hospital Anxiety and Depression scale (HADS). Autoantibodies were measured and candidate genes (CaSR, AIRE, GATA3 and 22q11-deletion) were sequenced for classification of etiology. RESULTS: We identified 522 patients (511 alive) and estimated overall prevalence at 102 per million divided among post-surgical HP (64 per million), non-surgical HP (30 per million) and pseudo-HP (8 per million). Non-surgical HP comprised autosomal dominant hypocalcemia (21%), autoimmune polyendocrine syndrome type 1 (17%), DiGeorge/22q11 deletion syndrome (15%), idiopathic HP (44%), and others, 4%. Among the 283 respondents (median age 53 years (range 9-89), 75% females), seven formerly classified as idiopathic were reclassified after genetic and immunological analyses, whereas 26 (17% of non-surgical HP) remained idiopathic. Most were treated with vitamin D (94%) and calcium (70%), and 10 received parathyroid hormone. HP patients scored significantly worse than the normative population on SF-36 and HADS; patients with post-surgical scored worse than those with non-surgical HP and pseudo-HP, especially on physical health. CONCLUSIONS: We found higher prevalence of non-surgical HP in Norway than reported elsewhere. Genetic testing and autoimmunity screening of idiopathic HP identified a specific cause in 21%. Further research is necessary to unravel the causes of idiopathic HP and to improve the reduced HRQoL reported by HP patients
Pedestrian, Crowd, and Evacuation Dynamics
This contribution describes efforts to model the behavior of individual
pedestrians and their interactions in crowds, which generate certain kinds of
self-organized patterns of motion. Moreover, this article focusses on the
dynamics of crowds in panic or evacuation situations, methods to optimize
building designs for egress, and factors potentially causing the breakdown of
orderly motion.Comment: This is a review paper. For related work see http://www.soms.ethz.c
A longitudinal follow-up of autoimmune polyendocrine syndrome type 1
Source:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4971337/Context:
Autoimmune polyendocrine syndrome type 1 (APS1) is a childhood-onset monogenic disease defined
by the presence of two of the three major components: hypoparathyroidism, primary adrenocortical insuffi-
ciency, and chronic mucocutaneous candidiasis (CMC). Information on longitudinal follow-up of APS1 is sparse.
Objective:
To describe the phenotypes of APS1 and correlate the clinical features with autoantibody profiles and
autoimmune regulator (
AIRE)
mutations during extended follow-up (1996â2016).
Patients:
All known Norwegian patients with APS1.
Results:
Fifty-two patients from 34 families were identified. The majority presented with one of the major disease
components during childhood. Enamel hypoplasia, hypoparathyroidism, and CMC were the most frequent compo-
nents.Withage,mostpatientspresentedthreetofivediseasemanifestations,althoughsomehadmilderphenotypes
diagnosed in adulthood. Fifteen of the patients died during follow-up (median age at death, 34 years) or were
deceasedsiblingswithahighprobabilityofundisclosedAPS1.Allexceptthreehadinterferon-
)autoantibodies,and
allhadorgan-specificautoantibodies.Themostcommon
AIRE
mutationwasc.967_979del13,foundinhomozygosity
in 15 patients. A mild phenotype was associated with the splice mutation c.879
1G
A. Primary adrenocortical
insufficiency and type 1 diabetes were associated with protective human leucocyte antigen genotypes.
Conclusions:
Multiple presumable autoimmune manifestations, in particular hypoparathyroidism, CMC, and
enamel hypoplasia, should prompt further diagnostic workup using autoantibody analyses (eg, interferon-
)
and
AIRE
sequencing to reveal APS1, even in adults. Treatment is complicated, and mortality is high. Structured
follow-up should be performed in a specialized center
Genome-wide copy number variation (CNV) in patients with autoimmune Addison's disease
<p>Abstract</p> <p>Background</p> <p>Addison's disease (AD) is caused by an autoimmune destruction of the adrenal cortex. The pathogenesis is multi-factorial, involving genetic components and hitherto unknown environmental factors. The aim of the present study was to investigate if gene dosage in the form of copy number variation (CNV) could add to the repertoire of genetic susceptibility to autoimmune AD.</p> <p>Methods</p> <p>A genome-wide study using the Affymetrix GeneChip<sup>ÂŽ </sup>Genome-Wide Human SNP Array 6.0 was conducted in 26 patients with AD. CNVs in selected genes were further investigated in a larger material of patients with autoimmune AD (n = 352) and healthy controls (n = 353) by duplex Taqman real-time polymerase chain reaction assays.</p> <p>Results</p> <p>We found that low copy number of <it>UGT2B28 </it>was significantly more frequent in AD patients compared to controls; conversely high copy number of <it>ADAM3A </it>was associated with AD.</p> <p>Conclusions</p> <p>We have identified two novel CNV associations to <it>ADAM3A </it>and <it>UGT2B28 </it>in AD. The mechanism by which this susceptibility is conferred is at present unclear, but may involve steroid inactivation (<it>UGT2B28</it>) and T cell maturation (<it>ADAM3A</it>). Characterization of these proteins may unravel novel information on the pathogenesis of autoimmunity.</p
Traffic and Related Self-Driven Many-Particle Systems
Since the subject of traffic dynamics has captured the interest of
physicists, many astonishing effects have been revealed and explained. Some of
the questions now understood are the following: Why are vehicles sometimes
stopped by so-called ``phantom traffic jams'', although they all like to drive
fast? What are the mechanisms behind stop-and-go traffic? Why are there several
different kinds of congestion, and how are they related? Why do most traffic
jams occur considerably before the road capacity is reached? Can a temporary
reduction of the traffic volume cause a lasting traffic jam? Under which
conditions can speed limits speed up traffic? Why do pedestrians moving in
opposite directions normally organize in lanes, while similar systems are
``freezing by heating''? Why do self-organizing systems tend to reach an
optimal state? Why do panicking pedestrians produce dangerous deadlocks? All
these questions have been answered by applying and extending methods from
statistical physics and non-linear dynamics to self-driven many-particle
systems. This review article on traffic introduces (i) empirically data, facts,
and observations, (ii) the main approaches to pedestrian, highway, and city
traffic, (iii) microscopic (particle-based), mesoscopic (gas-kinetic), and
macroscopic (fluid-dynamic) models. Attention is also paid to the formulation
of a micro-macro link, to aspects of universality, and to other unifying
concepts like a general modelling framework for self-driven many-particle
systems, including spin systems. Subjects such as the optimization of traffic
flows and relations to biological or socio-economic systems such as bacterial
colonies, flocks of birds, panics, and stock market dynamics are discussed as
well.Comment: A shortened version of this article will appear in Reviews of Modern
Physics, an extended one as a book. The 63 figures were omitted because of
storage capacity. For related work see http://www.helbing.org
Development of a Disease-Specific Quality of Life Questionnaire in Addisonâs Disease
Context: Patients with Addisonâs disease reproducibly self-report impairment in specific dimensions of general well-being questionnaires, suggesting particular deficiencies in health-related quality-of-life (HRQoL). Objective:Wesought to develop an Addisonâs disease-specific questionnaire (AddiQoL) that could better quantify altered well-being and treatment effects. Design, Setting, Patients, Intervention, and Outcomes: We reviewed the literature to identify HRQoL issues in Addisonâs disease and interviewed patients and their partners in-depth to explore various symptom domains. A list of items was generated, and nine expert clinicians and five expert patients assessed the list for impact and clarity. A preliminary questionnaire was presented to 100 Addisonâs outpatients; the number of items was reduced after analysis of the distribution of the responses. The final questionnaire responses were assessed by Cronbachâs and Rasch analysis. Results and Interpretation: Published studies of HRQoL in Addisonâs disease indicated reduced vitality and general health perception and limitations in physical and emotional functioning. In-depth interviews of 14 patients and seven partners emphasized the impact of the disease on the emotional domain. Seventy HRQoL items were generated; after the expert consultation process and pretesting in 100 patients, the number of items was reduced to 36. Eighty-six patients completed the final questionnaire; the responses showed high internal consistency with Cronbachâs 0.95 and Person Separation Index 0.94 (Rasch analysis). Conclusions: We envisage AddiQoL having utility in trials of hormone replacement and management of patients with Addisonâs disease, analogous to similar questionnaires in GH deficiency (AGHDA) and acromegaly (AcroQoL)