The Coming Boom in Computer Loads

Computers and other electronic equipment now consume as much electricity as electric steel furnaces, and their growth shows no signs of slowing. Utilities are active participants in the computer revolution. Northeast Utilities, for example, reports that 20% of electricity use in a typical new office building in its service area goes to computers. Given the expected growth in computers and computer loads, this technology deserves greater attention from utility planners and other energy analysts. It is shown that the commercial sector has been the largest contributor to kilowatt-hour (kwh) sales growth and that new uses within the commercial sector have accounted for the biggest portion of this growth. Confirming this conclusion are a 4-year Department of Energy-funded study of the Park Plaza Building office tower and a 1985 study of 181 office buildings by Northwest Utilities. A prospective study suggests that computers could account for as much as 150 billion kwh by the early 1990s

The upper critical field of filamentary Nb3Sn conductors

We have examined the upper critical field of a large and representative set of present multi-filamentary Nb3Sn wires and one bulk sample over a temperature range from 1.4 K up to the zero field critical temperature. Since all present wires use a solid-state diffusion reaction to form the A15 layers, inhomogeneities with respect to Sn content are inevitable, in contrast to some previously studied homogeneous samples. Our study emphasizes the effects that these inevitable inhomogeneities have on the field-temperature phase boundary. The property inhomogeneities are extracted from field-dependent resistive transitions which we find broaden with increasing inhomogeneity. The upper 90-99 % of the transitions clearly separates alloyed and binary wires but a pure, Cu-free binary bulk sample also exhibits a zero temperature critical field that is comparable to the ternary wires. The highest mu0Hc2 detected in the ternary wires are remarkably constant: The highest zero temperature upper critical fields and zero field critical temperatures fall within 29.5 +/- 0.3 T and 17.8 +/- 0.3 K respectively, independent of the wire layout. The complete field-temperature phase boundary can be described very well with the relatively simple Maki-DeGennes model using a two parameter fit, independent of composition, strain state, sample layout or applied critical state criterion.Comment: Accepted Journal of Applied Physics Few changes to shorten document, replaced eq. 7-

The personal experience of parenting a child with Juvenile Huntington’s Disease: perceptions across Europe

The study reported here presents a detailed description of what it is like to parent a child with juvenile Huntington’s disease in families across four European countries. Its primary aim was to develop and extend findings from a previous UK study. The study recruited parents from four European countries: Holland, Italy, Poland and Sweden,. A secondary aim was to see the extent to which the findings from the UK study were repeated across Europe and the degree of commonality or divergence across the different countries. Fourteen parents who were the primary caregiver took part in a semistructured interview. These were analyzed using an established qualitative methodology, interpretative phenomenological analysis. Five analytic themes were derived from the analysis: the early signs of something wrong; parental understanding of juvenile Huntington’s disease; living with the disease; other people’s knowledge and understanding; and need for support. These are discussed in light of the considerable convergence between the experiences of families in the United Kingdom and elsewhere in Europe

Population stratification may bias analysis of PGC-1α as a modifier of age at Huntington disease motor onset

Huntington’s disease (HD) is an inherited neurodegenerative disorder characterized by motor, cognitive and behavioral disturbances, caused by the expansion of a CAG trinucleotide repeat in the HD gene. The CAG allele size is the major determinant of age at onset (AO) of motor symptoms, although the remaining variance in AO is highly heritable. The rs7665116 SNP in PPARGC1A, encoding the mitochondrial regulator PGC-1α, has been reported to be a significant modifier of AO in three European HD cohorts, perhaps due to affected cases from Italy. We attempted to replicate these findings in a large collection of (1,727) HD patient DNA samples of European origin. In the entire cohort, rs7665116 showed a significant effect in the dominant model (p value = 0.008) and the additive model (p value = 0.009). However, when examined by origin, cases of Southern European origin had an increased rs7665116 minor allele frequency (MAF), consistent with this being an ancestry-tagging SNP. The Southern European cases, despite similar mean CAG allele size, had a significantly older mean AO (p < 0.001), suggesting population-dependent phenotype stratification. When the generalized estimating equations models were adjusted for ancestry, the effect of the rs7665116 genotype on AO decreased dramatically. Our results do not support rs7665116 as a modifier of AO of motor symptoms, as we found evidence for a dramatic effect of phenotypic (AO) and genotypic (MAF) stratification among European cohorts that was not considered in previously reported association studies. A significantly older AO in Southern Europe may reflect population differences in genetic or environmental factors that warrant further investigation

Candidate glutamatergic and dopaminergic pathway gene variants do not influence Huntington’s disease motor onset

Huntington’s disease (HD) is a neurodegenerative disorder characterized by motor, cognitive, and behavioral disturbances. It is caused by the expansion of the HTT CAG repeat, which is the major determinant of age at onset (AO) of motor symptoms. Aberrant function of N-methyl-D-aspartate receptors and/or overexposure to dopamine has been suggested to cause significant neurotoxicity, contributing to HD pathogenesis. We used genetic association analysis in 1,628 HD patients to evaluate candidate polymorphisms in N-methyl-D-aspartate receptor subtype genes (GRIN2A rs4998386 and rs2650427, and GRIN2B rs1806201) and functional polymorphisms in genes in the dopamine pathway (DAT1 3′ UTR 40-bp variable number tandem repeat (VNTR), DRD4 exon 3 48-bp VNTR, DRD2 rs1800497, and COMT rs4608) as potential modifiers of the disease process. None of the seven polymorphisms tested was found to be associated with significant modification of motor AO, either in a dominant or additive model, after adjusting for ancestry. The results of this candidate-genetic study therefore do not provide strong evidence to support a modulatory role for these variations within glutamatergic and dopaminergic genes in the AO of HD motor manifestations

Hormone replacement therapy before breast cancer diagnosis significantly reduces the overall death rate compared with never-use among 984 breast cancer patients

Nine hundred and eighty-four breast cancer patients were interviewed regarding exogenous hormonal use. This represents a random sample of breast cancer patients in Southern Sweden referred to the Department of Oncology at Lund for treatment between 1978 and 1997 (excluding 1980 and 1981) with a 100% follow-up. Ever-use of hormone replacement therapy (HRT) prior to diagnosis was significantly associated with a longer overall survival in women with their breast cancer diagnosed at ages 45 and above, relative risk (RR) of dying 0.73 (95% confidence interval (CI) 0.62-0.87; P = 0.0005). Ever use of HRT prior to breast cancer diagnosis was significantly positively associated with overall longer survival after adjustment for T-stage, N-stage, M-stage, year of diagnosis and age at diagnosis, RR of dying 0.78 (95% CI 0.65-0.93; P = 0.006). Hormone replacement therapy use and oestrogen receptor positivity were independently significantly associated with overall longer survival, P = 0.005 and P < 0.0001, respectively, in one model. HRT use and progesterone receptor positivity were also independently significantly associated with longer overall survival, P = 0.003 and P = 0.0003, respectively, in another model. The mode of diagnosis was known in 705 women. Mammography screening was not more common among HRT users compared with never-users, where this information was available. Both mammography screening and HRT use were independently associated with longer survival, P = 0.002 and P = 0.038 respectively

International mixed methods study protocol to develop a patient-reported outcome measure for all types of chronic wounds (the WOUND-Q)

INTRODUCTION: Most patient-reported outcome measures (PROM) for chronic wounds are specific to a single wound type (eg, pressure ulcer) or part of the body. A barrier to outcome assessment in wound care and research is the lack of a rigorously designed PROM that can be used across wound types and locations. This mixed method study describes the protocol for an international collaboration to develop and validate a new PROM called the WOUND-Q for adults with chronic wounds. METHODS AND ANALYSIS: In phase I, the qualitative approach of interpretive description is used to elicit concepts important to people with wounds regarding outcome. Participants from Canada, Denmark, the Netherlands, and the USA are aged 18 years and older and have a wound that has lasted 3 months or longer. Interviews are digitally recorded, transcribed and coded. A conceptual framework and preliminary item pool are developed from the qualitative dataset. Draft scales are formed to cover important themes in the conceptual framework. These scales are refined using feedback from people with chronic wounds and wound care experts. After refinement, the scales are translated into Danish and Dutch, following rigorous methods, to prepare for an international field-test study. In phase II, data are collected in Canada, Denmark, the Netherlands, and the USA. An international sample of people with a large variety of chronic wounds complete the WOUND-Q. Rasch Measurement Theory analysis is used to identify the best subset of items to retain for each scale and to

Study Protocol for the Development of a European eHealth Platform to Improve Quality of Life in Individuals With Huntington's Disease and Their Partners (HD-eHelp Study): A User-Centered Design Approach

Background: Huntington's disease (HD) is an autosomal dominant neurodegenerative disease that affects the quality of life (QoL) of HD gene expansion carriers (HDGECs) and their partners. Although HD expertise centers have been emerging across Europe, there are still some important barriers to care provision for those affected by this rare disease, including transportation costs, geographic distance of centers, and availability/accessibility of these services in general. eHealth seems promising in overcoming these barriers, yet research on eHealth in HD is limited and fails to use telehealth services specifically designed to fit the perspectives and expectations of HDGECs and their families. In the European HD-eHelp study, we aim to capture the needs and wishes of HDGECs, partners of HDGECs, and health care providers (HCPs) in order to develop a multinational eHealth platform targeting QoL of both HDGECs and partners at home.Methods: We will employ a participatory user-centered design (UCD) approach, which focusses on an in-depth understanding of the end-users' needs and their contexts. Premanifest and manifest adult HDGECs (n = 76), partners of HDGECs (n = 76), and HCPs (n = 76) will be involved as end-users in all three phases of the research and design process: (1) Exploration and mapping of the end-users' needs, experiences and wishes; (2) Development of concepts in collaboration with end-users to ensure desirability; (3) Detailing of final prototype with quick review rounds by end-users to create a positive user-experience. This study will be conducted in the Netherlands, Germany, Czech Republic, Italy, and Ireland to develop and test a multilingual platform that is suitable in different healthcare systems and cultural contexts.Discussion: Following the principles of UCD, an innovative European eHealth platform will be developed that addresses the needs and wishes of HDGECs, partners and HCPs. This allows for high-quality, tailored care to be moved partially into the participants' home, thereby circumventing some barriers in current HD care provision. By actively involving end-users in all design decisions, the platform will be tailored to the end-users' unique requirements, which can be considered pivotal in eHealth services for a disease as complex and rare as HD

Dose-dependent improvement of myoclonic hyperkinesia due to Valproic acid in eight Huntington's Disease patients: a case series

BACKGROUND: Chorea in Huntington's Disease (HD) is usually treated with antidopaminergic neuroleptics like haloperidol, olanzapine and tiaprid or dopamine depleting drugs like tetrabenazine. Some patients with hyperkinesia, however, react to treatment with antidopaminergic drugs by developing extrapyramidal side effects. In earlier studies valproic acid showed no beneficial effect on involuntary choreatic movements. Myoclonus is rare in HD and is often overseen or misdiagnosed as chorea. METHODS: In this report, we present eight patients whose main symptom is myoclonic hyperkinesia. All patients were treated with valproic acid and scored by using the Unified Huntington's Disease Rating Scale (UHDRS) motor score before and after treatment. In addition to this, two patients agreed to be videotaped. RESULTS: In seven patients myoclonus and, therefore the UHDRS motor score improved in a dose dependent manner. In three of these patients antidopaminergic medication could be reduced. CONCLUSION: In the rare subgroup of HD patients suffering from myoclonic hyperkinesia, valproic acid is a possible alternative treatment

Mutant Huntingtin induces activation of the Bcl-2/adenovirus E1B 19-kDa interacting protein (BNip3)

Huntington's disease (HD) is a neurodegenerative disorder characterized by progressive neuronal death in the basal ganglia and cortex. Although increasing evidence supports a pivotal role of mitochondrial dysfunction in the death of patients' neurons, the molecular bases for mitochondrial impairment have not been elucidated. We provide the first evidence of an abnormal activation of the Bcl-2/adenovirus E1B 19-kDa interacting protein 3 (BNip3) in cells expressing mutant Huntingtin. In this study, we show an abnormal accumulation and dimerization of BNip3 in the mitochondria extracted from human HD muscle cells, HD model cell cultures and brain tissues from HD model mice. Importantly, we have shown that blocking BNip3 expression and dimerization restores normal mitochondrial potential in human HD muscle cells. Our data shed light on the molecular mechanisms underlying mitochondrial dysfunction in HD and point to BNip3 as a new potential target for neuroprotective therapy in HD