bluuebunny/crossref_metadata_2025_split huggingface dataset:
HEALTH TECHNOLOGY ASSESSMENT IN POLAND AND SCOTLAND: COMPARISON OF PROCESS AND DECISIONS
Authors: Kolasa Katarzyna , Wasiak Radek 
Published: May 2012

Objectives: We compared Polish and Scottish Health Technology Assessment (HTA) process in order to elicit recommendations for future development of HTA methodological guidelines in Poland.Methods: We studied the differences between Polish and Scottish HTA methodological guidelines. HTA recommendations issued by Polish HTA agency (AHTAPol) in the period January 1 through December 31, 2008, were benchmarked to HTA guidance published by Scottish Medical Consortium (SMC) for the same drug technology.Results: The Scottish HTA methodological guidelines were more instructive in terms of clinical and economic evaluations than Polish guidelines. SMC evaluated forty-eight of sixty-eight drug technologies appraised by AHTAPoL. There were thirty drug technologies that received similar guidance in both countries and eighteen with contradictory HTA recommendations. In Scotland, there were more positive HTA recommendations than there were in Poland. While comments about efficacy or safety were commonplace among reasons for negative recommendations in Poland, insufficient justification of treatment's cost in relation to benefits was the most often cited reason for rejection in Scotland. SMC tended to recommend restricted use to specific sub-populations for several drug technologies negatively appraised by AHTAPoL.Conclusions: The comparison between SMC and AHTAPoL suggests that there is potential room of improvement of the Polish HTA methodological guidelines. Comparative effectiveness and safety, subgroup analysis, and adaptation of models to local settings were identified as key areas for further development of Polish HTA methodological guidelines.
Effects of HIV and Early Life Stress on Amygdala Morphometry and Neurocognitive Function
Authors: Clark Uraina S. , Cohen Ronald A. , Sweet Lawrence H. , Gongvatana Assawin , Devlin Kathryn N. , Hana George N. , Westbrook Michelle L. , Mulligan Richard C. , Jerskey Beth A. , White Tara L. , Navia Bradford , Tashima Karen T. 
Published: May 2012

AbstractBoth HIV infection and high levels of early life stress (ELS) have been related to abnormalities in frontal-subcortical structures, yet the combined effects of HIV and ELS on brain structure and function have not been previously investigated. In this study we assessed 49 non-demented HIV-seropositive (HIV+) and 47 age-matched HIV-seronegative healthy control (HC) adults. Levels of ELS exposure were quantified and used to define four HIV-ELS groups: HC Low-ELS (N= 20); HC High-ELS (N= 27); HIV+ Low-ELS (N= 24); HIV+ High-ELS (N= 25). An automated segmentation tool measured volumes of brain structures known to show HIV-related or ELS-related effects; a brief neurocognitive battery was administered. A significant HIV-ELS interaction was observed for amygdala volumes, which was driven by enlargements in HIV+ High-ELS participants. The HIV+ High-ELS group also demonstrated significant reductions in psychomotor/processing speed compared with HC Low-ELS. Regression analyses in the HIV+ group revealed that amygdala enlargements were associated with higher ELS, lower nadir CD4 counts, and reduced psychomotor/processing speed. Our results suggest that HIV infection and high ELS interact to increase amygdala volume, which is associated with neurocognitive dysfunction in HIV+ patients. These findings highlight the lasting neuropathological influence of ELS and suggest that high ELS may be a significant risk factor for neurocognitive impairment in HIV-infected individuals. (JINS, 2012,19, 1–12)
Real‐time, reliable magnitudes for large earthquakes from 1 Hz GPS precise point positioning: The 2011 Tohoku‐Oki (Japan) earthquake
Authors: Wright Tim J. , Houlié Nicolas , Hildyard Mark , Iwabuchi Tetsuya 
Published: May 2012

The early warning issued after the onset of the Mw9.0 Tohoku‐Oki earthquake significantly underestimated its magnitude, saturating, 120 seconds after the earthquake began, at Mw8.1. Here we investigate whether real‐time deformation data from Japan's dense network of continuously‐recording Global Positioning System (GPS) stations could have been used to provide a more reliable rapid estimate of the earthquake's magnitude, and ultimately a more robust tsunami forecast. We use precise point positioning in real‐time mode with broadcast clock and orbital corrections to give station positions every 1 s. We then carry out a simple static inversion on a subset of stations to determine the portion of the fault that slipped and the earthquake magnitude. Unlike most previous methods, our method produces estimates of seismic moment before the earthquake rupture has completed. We find that the deformation data allow a robust magnitude estimate just ∼100 s after the earthquake onset. We also investigated the density of stations required for a robust moment magnitude estimate. Fewer than 1 station every 100 km are needed. We recommend that GPS data be incorporated into earthquake early warning systems for regions at threat from large magnitude earthquakes and tsunamis.
The G2385R variant of leucine-rich repeat kinase 2 associated with Parkinson's disease is a partial loss-of-function mutation
Authors: Rudenko Iakov N. , Kaganovich Alice , Hauser David N. , Beylina Aleksandra , Chia Ruth , Ding Jinhui , Maric Dragan , Jaffe Howard , Cookson Mark R. 
Published: May 2012

Autosomal-dominant missense mutations in LRRK2 (leucine-rich repeat kinase 2) are a common genetic cause of PD (Parkinson's disease). LRRK2 is a multidomain protein with kinase and GTPase activities. Dominant mutations are found in the domains that have these two enzyme activities, including the common G2019S mutation that increases kinase activity 2–3-fold. However, there is also a genetic variant in some populations, G2385R, that lies in a C-terminal WD40 domain of LRRK2 and acts as a risk factor for PD. In the present study we show that the G2385R mutation causes a partial loss of the kinase function of LRRK2 and deletion of the C-terminus completely abolishes kinase activity. This effect is strong enough to overcome the kinase-activating effects of the G2019S mutation in the kinase domain. Hsp90 (heat-shock protein of 90 kDa) has an increased affinity for the G2385R variant compared with WT (wild-type) LRRK2, and inhibition of the chaperone binding combined with proteasome inhibition leads to association of mutant LRRK2 with high molecular mass native fractions that probably represent proteasome degradation pathways. The loss-of-function of G2385R correlates with several cellular phenotypes that have been proposed to be kinase-dependent. These results suggest that the C-terminus of LRRK2 plays an important role in maintaining enzymatic function of the protein and that G2385R may be associated with PD in a way that is different from kinase-activating mutations. These results may be important in understanding the differing mechanism(s) by which mutations in LRRK2 act and may also have implications for therapeutic strategies for PD.
Nitric oxide-dependent CYP2B degradation is potentiated by a cytokine-regulated pathway and utilizes the immunoproteasome subunit LMP2
Authors: Sun Haiyan , Lee Choon-myung , Tripathi Shweta , Kim Kyung-Bo , Morgan Edward T. 
Published: May 2012

CYP2B proteins in rat hepatocytes undergo NO-dependent proteolytic degradation, but the mechanisms and the reasons for the specificity towards only certain P450 (cytochrome P450) enzymes are yet unknown. In the present study we found that down-regulation of CYP2B proteins by the NO donor NOC-18 is accelerated by pretreatment of the hepatocytes with IL-1 (interleukin-1β) in the presence of an NO synthase inhibitor, suggesting that an NO-independent action of IL-1 contributes to the lability of CYP2B proteins. The immunoproteasome subunit LMP2 (large multifunctional peptidase 2) was significantly expressed in hepatocytes under basal conditions, and IL-1 induced LMP2 within 6–12 h of treatment. CYP2B protein degradation in response to IL-1 was attenuated by the selective LMP2 inhibitor UK-101, but not by the LMP7 inhibitor IPSI. The results show that LMP2 contributes to the NO-dependent degradation of CYP2B proteins, and suggest that induction of LMP2 may be involved in the potentiation of this degradation by IL-1.
TNF-related apoptosis-inducing ligand significantly attenuates metabolic abnormalities in high-fat-fed mice reducing adiposity and systemic inflammation
Authors: Bernardi Stella , Zauli Giorgio , Tikellis Christos , Candido Riccardo , Fabris Bruno , Secchiero Paola , Cooper Mark E. , Thomas Merlin C. 
Published: May 2012

TRAIL [TNF (tumour necrosis factor)-related apoptosis-inducing ligand] has recently been shown to ameliorate the natural history of DM (diabetes mellitus). It has not been determined yet whether systemic TRAIL delivery would prevent the metabolic abnormalities due to an HFD [HF (high-fat) diet]. For this purpose, 27 male C57bl6 mice aged 8 weeks were randomly fed on a standard diet, HFD or HFD+TRAIL for 12 weeks. TRAIL was delivered weekly by intraperitoneal injection. Body composition was evaluated; indirect calorimetry studies, GTT (glucose tolerance test) and ITT (insulin tolerance test) were performed. Pro-inflammatory cytokines, together with adipose tissue gene expression and apoptosis, were measured. TRAIL treatment reduced significantly the increased adiposity associated with an HFD. Moreover, it reduced significantly hyperglycaemia and hyperinsulinaemia during a GTT and it improved significantly the peripheral response to insulin. TRAIL reversed the changes in substrate utilization induced by the HFD and ameliorated skeletal muscle non-esterified fatty acids oxidation rate. This was associated with a significant reduction of pro-inflammatory cytokines together with a modulation of adipose tissue gene expression and apoptosis. These findings shed light on the possible anti-adipogenic and anti-inflammatory effects of TRAIL and open new therapeutic possibilities against obesity, systemic inflammation and T2DM (Type 2 DM).
The Awareness of the Profession of Audiology Among Entering College Students
Authors: Emanuel Diana C. , Donai Jeremy J. , Araj Chris F. 
Published: May 2012

Purpose
The purpose of this study was to develop and pilot test a survey of entering college students' awareness of the profession of audiology and to report the preliminary results of the survey.

Method
A survey was developed and administered in 2003 at the California University of Pennsylvania. A modified survey was administered in 2009. Survey questions asked students to identify what audiologists do and the education requirements to become an audiologist.

Results
Seventeen percent of the students self-reported that they knew what an audiologist did and were able to accurately describe the profession. Approximately 30% of the students learned about audiology from family/friends. Students reported selecting their major based on interest in a specific field and not on market-driven forces such as job opportunities and salary.

Conclusion
Future surveys should be conducted to confirm the extent of the lack of visibility of audiology as a profession and to serve as a metric for the efficacy of future marketing efforts in the profession.
Monteverdi, Early Opera and a Question of Genre: The Case of Andromeda (1620)
Authors: Carter Tim 
Published: May 2012

ABSTRACTIn 1985, Albi Rosenthal reported his discovery of a printed libretto for the opera Andromeda, composed by Monteverdi for performance in Mantua in Carnival 1620. This libretto deserves a new examination for its dramatic content, its likely musical setting (now lost) and some fundamental questions of genre. Its patron, Prince Vincenzo Gonzaga, used the librettist Hercole Marliani to broker his self-fashioning by imitating both Monteverdi's Orfeo (1607), supported by Vincenzo's elder brother, and Arianna (1608), which in effect belonged to the prince's parents. Monteverdi was typically slow to produce the score. The customary explanation is his disenchantment with Mantua and his new duties at St Mark's, Venice. However, we now see that both the Gonzagas and Monteverdi used Andromeda, like others of his Mantuan-commissioned works, as a bargaining chip in a complex exchange of obligations and favours typical of the courtly world to which the composer still belonged.
SALIGN: a web server for alignment of multiple protein sequences and structures
Authors: Braberg Hannes , Webb Benjamin M. , Tjioe Elina , Pieper Ursula , Sali Andrej , Madhusudhan M.S. 
Published: May 2012

Abstract
Summary: Accurate alignment of protein sequences and/or structures is crucial for many biological analyses, including functional annotation of proteins, classifying protein sequences into families, and comparative protein structure modeling. Described here is a web interface to SALIGN, the versatile protein multiple sequence/structure alignment module of MODELLER. The web server automatically determines the best alignment procedure based on the inputs, while allowing the user to override default parameter values. Multiple alignments are guided by a dendrogram computed from a matrix of all pairwise alignment scores. When aligning sequences to structures, SALIGN uses structural environment information to place gaps optimally. If two multiple sequence alignments of related proteins are input to the server, a profile–profile alignment is performed. All features of the server have been previously optimized for accuracy, especially in the contexts of comparative modeling and identification of interacting protein partners.
Availability: The SALIGN web server is freely accessible to the academic community at http://salilab.org/salign. SALIGN is a module of the MODELLER software, also freely available to academic users (http://salilab.org/modeller).
Contact: sali@salilab.org; madhusudhan@bii.a-star.edu.sg
Effects of Brans from Specialty Sorghum Varieties on In Vitro Starch Digestibility of Soft and Hard Sorghum Endosperm Porridges
Authors: Austin Dilek Lemlioglu , Turner Nancy D. , McDonough Cassandra M. , Rooney Lloyd W. 
Published: May 2012

ABSTRACTBrans of specialty sorghum varieties (high tannin, black, and black with tannin) were used to investigate the effects of sorghum phenolic compounds on starch digestibility of soft and hard sorghum endosperm porridges. Endosperms of varieties with the highest and lowest grain hardness index were mixed with brans of specialty sorghum varieties in the ratio of 85:15 and cooked into porridges with distilled water using a Rapid Visco Analyzer. Brans of condensed tannin containing sorghum varieties (high‐tannin and black with tannin sorghums) significantly (P < 0.05) decreased starch digestibility and estimated glycemic index (EGI) and increased resistant starch (RS) content of endosperm porridges. However, the addition of phenolic‐rich tannin‐free (mostly anthocyanins) black sorghum bran significantly (P < 0.05) increased starch digestibility and EGI but did not affect RS content of endosperm porridges. The disparate effects with black bran may, in part, result from its larger particle size and different bran structure compared with other sorghum varieties evaluated. Thus, our study showed that not only presence of phenolic compounds in the brans but also structural differences of specialty sorghum brans can have significant effects on starch digestibility.
First Report of Pilidium concavum Causing Tan-Brown Leaf Spot on Strawberry in China
Authors: Geng W. L. , Hu P. , Ma Z. , Zhao X. Y. , Wei Y. M. 
Published: May 2012

In April 2011, a survey of diseases was conducted on strawberry plants grown in greenhouses in the town of Xingshou, Changping District, Beijing, China. A tan-brown leaf spot with the presence of pink spore masses was observed on older leaves of strawberry plants. In general, the leaf spots began as small, round, water-soaked lesions in the middle or on the margin of leaves, which enlarged gradually up to 1 to 3 cm in diameter and were circular or irregular and brown to dark brown. Occasionally, the center of some spots cracked in the middle lesion under dry conditions. Eventually, black sporodochia were produced on the upper surface of spots and exuded pink conidial masses under humid conditions. Fungal structures were taken directly from the diseased leaves and examined microscopically for morphological characteristics. Sporodochia, 172 to 451 × 138 to 343 μm, were dark and suborbicular. Conidiophores, 8.4 to 48.3 × 0.8 to 2.1 μm, were hyaline, unicellular, and cylindrical. Conidia, 3.1 to 10.2 × 1.5 to 3.0 μm, were hyaline, aseptate, and canoe-shaped to allantoid, forming singly. For further study, the fungus was isolated in pure culture on potato dextrose agar (PDA) medium from symptomatic leaf tissue. In culture, the mycelium was white at first and then changed to brownish. The sporodochia were light colored at first and turned brownish or almost black in older cultures. To identify the fungus, the ITS1-5.8S-ITS2 rDNA region of the isolate was amplified by PCR with primers ITS1 (5′-TCCGTAGGTGAACCTGCGG-3′) and ITS4 (5′-TCCTCCGCTTATTGATATGC-3′) and sequenced. The 462-nt sequence (GenBank Accession No. JQ995228) was identical to that of Pilidium concavum (1). To validate Koch's postulates, pathogenicity was tested by inoculating 20 leaves on 10 healthy strawberry plants with a mycelial plug from a 15-day-old colony (0.5 cm in diameter). Controls were treated with plugs of PDA medium. The inoculated and control plants were then maintained in growth chambers at 25°C (12 h of light per day, 80% humidity). After 12 days, 100% of the inoculated leaves showed symptoms identical to those observed on leaves in the field while the control leaves remained healthy. The original fungus was reisolated from inoculated leaves showing the symptoms. Thus, it was concluded that the fungus was the causal organism of the leaf spot. On the basis of morphological characteristics, molecular features, and pathogenicity tests, the pathogen of tan-brown leaf spot on strawberry was identified as P. concavum. To our knowledge, this is the first report of P. concavum causing tan-brown leaf spot on strawberry in China. This fungus was reported to cause leaf spot on Paeonia suffruticosa in China (2). It also caused tan-brown rot on strawberry fruit in our pathogenicity test. References: (1) L. Cardin et al. Plant Dis. 93:548, 2009. (2) Y. B. Duan et al. Plant Dis. 94:271, 2010.
Interobserver Agreement in Case History Evaluation in Carpal Tunnel Syndrome
Authors: Westerman Dewa , Kerkhoff Henk , Visser Gerhard H. , Kleyweg Rudolf P. 
Published: May 2012

Abstract

Objectives:
The case history is the cornerstone for the diagnosis of carpal tunnel syndrome (CTS). The value of neurological examination in CTS seems limited. In this study, we investigated the interobserver agreement in case history of CTS and the potential additional value of neurological examination.

Methods:
Case history was taken and neurological examination was done in all patients referred for a possible CTS during a 6-month period. This was done independently by 2 senior neurologists.

Results:
We studied 119 patients. The interobserver agreement for the conclusion of CTS after history was high (k = 0.79). Neurological examination rarely changed the diagnosis based on the case history.

Conclusions:
This study shows a high interobserver agreement in the diagnosis of CTS based on patient history alone. Neurological examination rarely changed this diagnosis, suggesting a prominent role for the case history and a limited role for neurological examination. This may have practical implications.
A Case of Monomelic Amyotrophy of the Upper Limb
Authors: Li Yuebing , Remmel Krista 
Published: May 2012

Abstract
Monomelic amyotrophy of the upper limb or Hirayama disease is mostly considered as an anterior horn disorder resulting from local ischemia, triggered by arterial compression from an anterior shifting of the posterior cervical dura upon neck flexion. However, such a dural shifting is not universally seen. We report on a Caucasian male patient who developed a slowly progressive unilateral distal hand weakness in his teens. His clinical and electromyographic findings were consistent with Hirayama disease. Local anterior cervical cord atrophy was observed without dural shifting on the dynamic magnetic resonance imaging. Axial magnetic resonance imaging demonstrated signal changes of “snake-eye” appearance in the cervical anterior horn region, similar to ischemic myelopathies caused by various etiologies. This case illustrated that even without dural shifting, a mechanism of anterior spinal cord ischemia could still be responsible for the pathogenesis of Hirayama disease.
Pharmacokinetics and tolerability of SRT2104, a first‐in‐class small molecule activator of SIRT1, after single and repeated oral administration in man
Authors: Hoffmann Ethan , Wald Jeff , Lavu Siva , Roberts John , Beaumont Claire , Haddad Jon , Elliott Peter , Westphal Christoph , Jacobson Eric 
Published: May 2012

AimSRT2104 is a novel, first‐in‐class, highly selective small molecule activator of the NAD + dependent deacetylase SIRT1. SRT2104 was dosed to healthy male and female volunteers in a series of phase 1 clinical studies that were designed to elucidate tolerability and pharmacokinetics associated with oral dosing to aid in dose selection for subsequent clinical trials.MethodsIn the first‐in‐human study, there was both a single dose phase and 7 day repeat dose phase. Doses used ranged from 0.03 to 3.0 g. A radioactive microtracer study was subsequently conducted to determine systemic clearance, bioavailability and preliminary metabolism, and a crossover study was conducted to determine the effect of gender, formulation and feeding state on SRT2104 pharmacokinetics.ResultsSRT2104 was well tolerated in all of these studies, with no serious adverse reactions observed. SRT2104 displayed a dose‐dependent, but sub‐proportional increase in exposure following single dose and repeated dose administration. Accumulation of three‐fold or less occurs after 7 days of repeat dosing. The mean bioavailability was circa 14% and the mean clearance was circa 400 ml min−1. Although there were no substantial effects on exposure resulting from gender or formulation differences, a notable food effect was observed, manifested as up to four‐fold increase in exposure parameters.ConclusionsIn the absence of an optimized formulation of SRT2104, the food effect can be used to maximize exposure in future clinical studies. Combined with the good tolerability of all doses demonstrated in these studies, the favourable selectivity profile of SRT2104 allows for the use of this SIRT1 modulator for target validation in the clinic.