bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development of omics-based clinical tests for prognosis and therapy selection: The challenge of achieving statistical robustness and clinical utility
Authors: McShane Lisa M , Polley Mei-Yin C 
Published: September 2013

Background Many articles have been published in biomedical journals reporting on the development of prognostic and therapy-guiding biomarkers or predictors developed from high-dimensional data generated by omics technologies. Few of these tests have advanced to routine clinical use. Purpose We discuss statistical issues in the development and evaluation of prognostic and therapy-guiding biomarkers and omics-based tests. Methods Concepts relevant to the development and evaluation of prognostic and therapy-guiding clinical tests are illustrated through discussion and examples. Some differences between statistical approaches for test evaluation and therapy evaluation are explained. The additional complexities introduced in the evaluation of omics-based tests are highlighted. Results Distinctions are made between clinical validity of a test and clinical utility. To establish clinical utility for prognostic tests, it is explained why absolute risk should be evaluated in addition to relative risk measures. The critical role of an appropriate control group is emphasized for evaluation of therapy-guiding tests. Common pitfalls in the development and evaluation of tests generated from high-dimensional omics data such as model overfitting and inappropriate methods for test performance evaluation are explained, and proper approaches are suggested. Limitations The cited references do not comprise an exhaustive list of useful references on this topic, and a systematic review of the literature was not performed. Instead, a few key points were highlighted and illustrated with examples drawn from the oncology literature. Conclusions Approaches for the development and statistical evaluation of clinical tests useful for predicting prognosis and selecting therapy differ from standard approaches for therapy evaluation. Proper evaluation requires an understanding of the clinical setting and what information is likely to influence clinical decisions. Specialized expertise relevant to building mathematical predictor models from high-dimensional data is helpful to avoid common pitfalls in the development and evaluation of omics-based tests.
A feasibility study and pilot randomised trial of a tailored prevention program to reduce falls in older people with mild dementia
Authors: Wesson Jacqueline , Clemson Lindy , Brodaty Henry , Lord Stephen , Taylor Morag , Gitlin Laura , Close Jacqueline 
Published: September 2013

Abstract

Background
People with dementia have a disproportionately high rate of falls and fractures and poorer outcomes, yet there is currently no evidence to guide falls prevention in this population.

Methods
A randomised trial design was used to test feasibility of study components and acceptability of a home hazard reduction and balance and strength exercise fall prevention program. The program was tailored to participant’s individual cognitive levels and implemented as a carer-supported intervention. Feasibility of recruitment, retention and implementation of intervention were recorded through observation and documented in field notes. Adherence, carer burden and use of task simplification strategies were also monitored. Outcome measures, collected at 12 weeks included physiological, fear of falling, cognitive and functional measures.

Results
Recruitment was achievable but may be more challenging in a multisite trial. Twenty two dyads of persons with mild dementia and their carers were randomised to intervention or usual care control group. Of 38 dyads referred to the study, there was a high rate of willingness to participate, with 6 (16%) declining and 10 (26%) not meeting inclusion criteria. The intervention was well received by participants and carers and adherence to both program components was very good. All participants implemented some home safety recommendations (range 19-80%) with half implementing 50% or more. At the end of 12 weeks, 72% of the intervention group were exercising. Both the rate of falling and the risk of a fall were lower in the intervention group but these findings were not significant (RR= 0.50 (95% CI 0.11-2.19). There were no differences in physiological outcome measures between the control and intervention groups. However results were influenced by the small study size and incomplete data primarily in the intervention group at follow up.

Conclusions
The pilot study was feasible and acceptable to people with mild dementia and their carers. The lessons learnt included: recruitment for a larger trial will require multiple approaches; home safety recommendations should provide a greater emphasis on environmental use compared with behavioural change; strategies to ensure an adequate dosage of exercise should be further explored. We recommend that intervention delivery incorporate an integrated occupational therapy and physiotherapy approach and that carers be provided with an individualised session to enhance dementia-specific skills in management and communication. A refined intervention should be tested in a randomised trial with an adequately powered sample size.

Trial registration
Australia and New Zealand Clinical Trials Registry 126100001049066
Chromobacterium haemolyticum-induced bacteremia in a healthy young man
Authors: Okada Megumi , Inokuchi Ryota , Shinohara Kazuaki , Matsumoto Akinori , Ono Yuko , Narita Masashi , Ishida Tokiya , Kazuki Chiba , Nakajima Susumu , Yahagi Naoki 
Published: September 2013

Abstract

Background
The genus Chromobacterium consists of 7 recognized species. Among those, only C. violaceum, commonly found in the soil and water of tropical and subtropical regions, has been shown to cause human infection. Although human infection is rare, C. violaceum can cause life-threatening sepsis, with metastatic abscesses, most frequently infecting those who are young and healthy.

Case presentation
We recently identified a case of severe bacteremia caused by Chromobacterium haemolyticum infection in a healthy young patient following trauma and exposure to river water, in Japan. The patient developed necrotizing fasciitis that was successfully treated with a fasciotomy and intravenous ciprofloxacin and gentamicin.

Conclusions

C. haemolyticum should be considered in the differential diagnosis of skin lesions that progressively worsen after trauma involving exposure to river or lake water, even in temperate regions. Second, early blood cultures for the isolation and identification of the causative organism were important for initiating proper antimicrobial therapy.
Localizing chronic Q fever: a challenging query
Authors: Barten Dennis G , Delsing Corine E , Keijmel Stephan P , Sprong Tom , Timmermans Janneke , Oyen Wim JG , Nabuurs-Franssen Marrigje H , Bleeker-Rovers Chantal P 
Published: September 2013

Abstract

Background
Chronic Q fever usually presents as endocarditis or endovascular infection. We investigated whether 18F-FDG PET/CT and echocardiography were able to detect the localization of infection. Also, the utility of the modified Duke criteria was assessed.

Methods
Fifty-two patients, who had an IgG titre of ≥ 1024 against C. burnetii phase I ≥ 3 months after primary infection or a positive PCR ≥ 1 month after primary infection, were retrospectively included. Data on serology, the results of all imaging studies, possible risk factors for developing proven chronic Q fever and clinical outcome were recorded.

Results
According to the Dutch consensus on Q fever diagnostics, 18 patients had proven chronic Q fever, 14 probable chronic Q fever, and 20 possible chronic Q fever. Of the patients with proven chronic Q fever, 22% were diagnosed with endocarditis, 17% with an infected vascular prosthesis, and 39% with a mycotic aneurysm. 56% of patients with proven chronic Q fever did not recall an episode of acute Q fever. Ten out of 13 18F-FDG PET/CT-scans in patients with proven chronic Q fever localized the infection. TTE and TEE were helpful in only 6% and 50% of patients, respectively.

Conclusions
If chronic Q fever is diagnosed, 18F-FDG PET/CT is a helpful imaging technique for localization of vascular infections due to chronic Q fever. Patients with proven chronic Q fever were diagnosed significantly more often with mycotic aneurysms than in previous case series. Definite endocarditis due to chronic Q fever was less frequently diagnosed in the current study. Chronic Q fever often occurs in patients without a known episode of acute Q fever, so clinical suspicion should remain high, especially in endemic regions.
The economic costs of malaria in children in three sub-Saharan countries: Ghana, Tanzania and Kenya
Authors: Sicuri Elisa , Vieta Ana , Lindner Leandro , Constenla Dagna , Sauboin Christophe 
Published: September 2013

AbstractBackgroundMalaria causes significant mortality and morbidity in sub-Saharan Africa (SSA), especially among children less than five years of age (U5 children). Although the economic burden of malaria in this region has been assessed previously, the extent and variation of this burden remains unclear. This study aimed to estimate the economic costs of malaria in U5 children in three countries (Ghana, Tanzania and Kenya).MethodsHealth system and household costs previously estimated were integrated with costs associated with co-morbidities, complications and productivity losses due to death. Several models were developed to estimate the expected treatment cost per episode per child, across different age groups, by level of severity and with or without controlling for treatment-seeking behaviour. Total annual costs (2009) were calculated by multiplying the treatment cost per episode according to severity by the number of episodes. Annual health system prevention costs were added to this estimate.ResultsHousehold and health system costs per malaria episode ranged from approximately US$ 5 for non-complicated malaria in Tanzania to US$ 288 for cerebral malaria with neurological sequelae in Kenya. On average, up to 55% of these costs in Ghana and Tanzania and 70% in Kenya were assumed by the household, and of these costs 46% in Ghana and 85% in Tanzania and Kenya were indirect costs. Expected values of potential future earnings (in thousands) lost due to premature death of children aged 0–1 and 1–4 years were US$ 11.8 and US$ 13.8 in Ghana, US$ 6.9 and US$ 8.1 in Tanzania, and US$ 7.6 and US$ 8.9 in Kenya, respectively. The expected treatment costs per episode per child ranged from a minimum of US$ 1.29 for children aged 2–11 months in Tanzania to a maximum of US$ 22.9 for children aged 0–24 months in Kenya. The total annual costs (in millions) were estimated at US$ 37.8, US$ 131.9 and US$ 109.0 nationwide in Ghana, Tanzania and Kenya and included average treatment costs per case of US$ 11.99, US$ 6.79 and US$ 20.54, respectively.ConclusionThis study provides important insight into the economic burden of malaria in SSA that may assist policy makers when designing future malaria control interventions.
Application of ATC/DDD methodology to eveluate of antibiotic use in a general hospital in Turkey
Authors: Sözen Hamdi , Gönen Ibak , Sözen Ayse , Kutlucan Ali , Kalemci Serdar , Sahan Murat 
Published: September 2013

AbstractBackgroundThe aim of this study is to evaluate in-house antibiotic use in a state hospital in Turkey with its cost, using the ATC/DDD index, which is an accepted standard method.MethodsThis study was performed as a point prevalence study in a state hospital with 372 beds. All in-house patients using antibiotics on July 19, 2011 were included in the study. Indications for antibiotic use and information about the patients were recorded on special forms. Antibiotic use and cost analysis were evaluated using the ATC/DDD index, which is also suggested by the WHO to be used in similar studies.Findings147 patients out of 308 patients who were in-house were identified to use antibiotics with appropriate indications for prophylaxis or treatment in 61% of the patients. The rate of appropriate antibiotic use was identified to be in 78%, while this rate was 38.9% in surgical clinics. The daily cost of the antibiotics consumed on the date of the study was calculated as 4104.79 TL (=2476.80 USD).DiscussionThe rate of inappropriate use of antibiotics seems to be high in our hospital. This will result in both increased costs and also increased nosocomial infection rates with resistant species. Infectious disease specialists should take more active roles in the in-house antibiotic use, hospitals should prepare and implement their own principles of antibiotic use, and microbiology laboratories should be used more effectively. These measures would decrease the conspicuous shortcomings in the antibiotic use.
Magnetoelectricity in CoFe2O4 nanocrystal-P(VDF-HFP) thin films
Authors: Liu Xiaohua , Liu Shuangyi , Han Myung-Geun , Zhao Lukas , Deng Haiming , Li Jackie , Zhu Yimei , Krusin-Elbaum Lia , O’Brien Stephen 
Published: September 2013

Abstract
Transition metal ferrites such as CoFe2O4, possessing a large magnetostriction coefficient and high Curie temperature (T
c > 600 K), are excellent candidates for creating magnetic order at the nanoscale and provide a pathway to the fabrication of uniform particle-matrix films with optimized potential for magnetoelectric coupling. Here, a series of 0–3 type nanocomposite thin films composed of ferrimagnetic cobalt ferrite nanocrystals (8 to 18 nm) and a ferroelectric/piezoelectric polymer poly(vinylidene fluoride-co-hexafluoropropene), P(VDF-HFP), were prepared by multiple spin coating and cast coating over a thickness range of 200 nm to 1.6 μm. We describe the synthesis and structural characterization of the nanocrystals and composite films by XRD, TEM, HRTEM, STEM, and SEM, as well as dielectric and magnetic properties, in order to identify evidence of cooperative interactions between the two phases. The CoFe2O4 polymer nanocomposite thin films exhibit composition-dependent effective permittivity, loss tangent, and specific saturation magnetization (M
s). An enhancement of the effective permittivity and saturation magnetization of the CoFe2O4-P(VDF-HFP) films was observed and directly compared with CoFe2O4-polyvinylpyrrolidone, a non-ferroelectric polymer-based nanocomposite prepared by the same method. The comparison provided evidence for the observation of a magnetoelectric effect in the case of CoFe2O4-P(VDF-HFP), attributed to a magnetostrictive/piezoelectric interaction. An enhancement of M
s up to +20.7% was observed at room temperature in the case of the 10 wt.% CoFe2O4-P(VDF-HFP) sample.
Size-regulated group separation of CoFe2O4 nanoparticles using centrifuge and their magnetic resonance contrast properties
Authors: Kang Jongeun , Lee Hyunseung , Kim Young-Nam , Yeom Areum , Jeong Heejeong , Lim Yong Taik , Hong Kwan Soo 
Published: September 2013

Abstract
Magnetic nanoparticle (MNP)-based magnetic resonance imaging (MRI) contrast agents (CAs) have been the subject of extensive research over recent decades. The particle size of MNPs varies widely and is known to influence their physicochemical and pharmacokinetic properties. There are two commonly used methods for synthesizing MNPs, organometallic and aqueous solution coprecipitation. The former has the advantage of being able to control the particle size more effectively; however, the resulting particles require a hydrophilic coating in order to be rendered water soluble. The MNPs produced using the latter method are intrinsically water soluble, but they have a relatively wide particle size distribution. Size-controlled water-soluble MNPs have great potential as MRI CAs and in cell sorting and labeling applications. In the present study, we synthesized CoFe2O4 MNPs using an aqueous solution coprecipitation method. The MNPs were subsequently separated into four groups depending on size, by the use of centrifugation at different speeds. The crystal shapes and size distributions of the particles in the four groups were measured and confirmed by transmission electron microscopy and dynamic light scattering. Using X-ray diffraction analysis, the MNPs were found to have an inverse spinel structure. Four MNP groups with well-selected semi-Gaussian-like diameter distributions were obtained, with measured T2 relaxivities (r
2) at 4.7 T and room temperature in the range of 60 to 300 mM−1s−1, depending on the particle size. This size regulation method has great promise for applications that require homogeneous-sized MNPs made by an aqueous solution coprecipitation method. Any group of the CoFe2O4 MNPs could be used as initial base cores of MRI T2 CAs, with almost unique T2 relaxivity owing to size regulation. The methodology reported here opens up many possibilities for biosensing applications and disease diagnosis.

PACS

75.75.Fk, 78.67.Bf, 61.46.Df
A 10-state model for an AMC scheme with repetition coding in mobile wireless networks
Authors: Quoc-Tuan Nguyen , Nguyen Dinh-Thong , Cong Lam Sinh 
Published: September 2013

Abstract
In modern broadband wireless access systems such as mobile worldwide interoperability for microwave access (WiMAX) and others, repetition coding is recommended for the lowest modulation level, in addition to the mandatory concatenated Reed-Solomon and convolutional code data coding, to protect vital control information from deep fades. This paper considers repetition coding as a time-diversity technique using maximum ratio combining (MRC) and proposes techniques to define and to calculate the repetition coding gain G
r and its effect on bit error rate (BER) under the two fading conditions: correlated lognormal shadowing and composite Rayleigh-lognormal fading also known as Suzuki fading. A variable-rate, variable-power 10-state finite-state Markov channel (FSMC) model is proposed for the implementation of the adaptive modulation and coding (AMC) scheme in mobile WiMAX to maximize its spectral efficiency under constant power constraints in the two fading mechanisms. Apart from the proposed FSMC model, the paper also presents two other significant contributions: one is an innovative technique for accurate matching of moment generating functions, necessary for the estimation of the probability density function of the combiner's output signal-to-noise ratio, and the other is efficient and fast expressions using Gauss-Hermite quadrature approximation for the calculation of BER of QPSK signal using MRC diversity reception.
Abscisic acid induced freezing tolerance in chilling-sensitive suspension cultures and seedlings of rice
Authors: Shinkawa Reiko , Morishita Aiko , Amikura Kumiko , Machida Rika , Murakawa Hiroki , Kuchitsu Kazuyuki , Ishikawa Masaya 
Published: September 2013

Abstract

Background
The role of abscisic acid (ABA) as a possible activator of cold acclimation process was postulated since endogenous levels of ABA increase temporarily or constitutively during cold-hardening. Exogenous application of ABA has been known to induce freezing tolerance at ambient temperatures in in vitro systems derived from cold hardy plants. Yet, some cell cultures acquired much greater freezing tolerance by ABA than by cold whilst maintaining active growth. This raises questions about the relationships among ABA, cold acclimation and growth cessation. To address this question, we attempted to 1) determine whether exogenous ABA can confer freezing tolerance in chilling-sensitive rice suspension cells and seedlings, which obviously lack the mechanisms to acquire freezing tolerance in response to cold; 2) characterize this phenomenon by optimizing the conditions and compare with the case of cold hardy bromegrass cells.

Results
Non-embryogenic suspension cells of rice suffered serious chilling injury when exposed to 4°C. When incubated with ABA at the optimal conditions (0.5-1 g cell inoculum, 75 μM ABA, 25-30°C, 7–10 days), they survived slow freezing (2°C/h) to −9.0 ~ −9.3°C (LT50: 50% killing temperature) while control cells were mostly injured at −3°C (LT50: -0.5 ~ −1.5°C). Ice-inoculation of the cell suspension at −3°C and survival determination by regrowth confirmed that ABA-treated rice cells survived extracellular freezing at −9°C. ABA-induced freezing tolerance did not require any exposure to cold and was best achieved at 25-30°C where the rice cells maintained high growth even in the presence of ABA. ABA treatment also increased tolerance to heat (43°C) as determined by regrowth. ABA-treated cells tended to have more augmented cytoplasm and/or reduced vacuole sizes compared to control cultures with a concomitant increase in osmolarity and a decrease in water content. ABA-treated (2–7 days) in vitro grown seedlings and their leaves survived slow freezing to −3°C with only marginal injury (LT50: -4°C) whereas untreated seedlings were killed at −3°C (LT50: -2°C).

Conclusions
The results indicate that exogenous ABA can induce some levels of freezing tolerance in chilling-sensitive rice cells and seedlings, probably by eliciting mechanisms different from low temperature-induced cold acclimation.
Mice with RyR1 mutation (Y524S) undergo hypermetabolic response to simvastatin
Authors: Knoblauch Mark , Dagnino-Acosta Adan , Hamilton Susan L 
Published: September 2013

Abstract

Background
Statins are widely used drugs for the treatment of hyperlipidemia. Though relatively safe, some individuals taking statins experience rhabdymyolysis, muscle pain, and cramping, a condition termed statin-induced myopathy (SIM). To determine if mutations in the skeletal muscle calcium (Ca2+) release channel, ryanodine receptor type 1 (RyR1), enhance the sensitivity to SIM we tested the effects of simvastatin, the statin that produces the highest incidence of SIM in humans, in mice with a mutation (Y524S, ‘YS’) in RyR1. This mutation is associated with malignant hyperthermia in humans. Exposure of mice with the YS mutation to mild elevations in environmental temperature produces a life-threatening hypermetabolic response (HMR) that is characterized by increased oxygen consumption (VO2), sustained muscle contractures, rhabdymyolysis, and elevated core body temperature.

Methods
We assessed the ability of simvastatin to induce a hypermetabolic response in the YS mice using indirect calorimetry and to alter Ca2+ release via RyR1 in isolated flexor digitorum brevis (FDB) fibers from WT and YS mice using fluorescent Ca2+ indicators. We also tested the ability of 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR) to protect against the simvastatin effects.

Results
An acute dose of simvastatin triggers a hypermetabolic response in YS mice. In isolated YS muscle fibers, simvastatin triggers an increase in cytosolic Ca2+ levels by increasing Ca2+ leak from the sarcoplasmic reticulum (SR). With higher simvastatin doses, a similar cytosolic Ca2+ increase occurs in wild type (WT) muscle fibers. Pre-treatment of YS and WT mice with AICAR prevents the response to simvastatin.

Conclusions
A mutation in RyR1 associated with malignant hyperthermia increases susceptibility to an adverse response to simvastatin due to enhanced Ca2+ release from the sarcoplasmic reticulum, suggesting that RyR1 mutations may underlie enhanced susceptibility to statin-induced myopathies. Our data suggest that AICAR may be useful for treating statin myopathies.