bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of Adopting Population Pharmacokinetics for Tailoring Prophylaxis in Haemophilia A Patients: A Historically Controlled Observational Study
Authors: Stemberger Michaela , Kallenbach Felix , Schmit Elisabeth , McEneny-King Alanna , Germini Federico , Yeung Cindy , Edginton Andrea , von Mackensen Sylvia , Kurnik Karin , Iorio Alfonso 
Published: January 2019

Background Performing individual pharmacokinetics (PK) studies in clinical practice can be simplified by adopting population PK-based profiling on limited post-infusion samples. The objective of this study was to assess the impact of population PK in tailoring prophylaxis in patients with haemophilia A.
Patients and Methods Individual weekly treatment plans were developed considering predicted plasma factor activity levels and patients' lifestyle. Patients were trained using a visual traffic-light scheme to help modulate their level of physical activity with respect to factor infusions timing. Annualized joint bleeding rate (ABJR), haemophilia-specific quality of life questionnaire for adults (Haemo-QoL-A) and factor utilization were measured for 12 months before and after tailoring, compared within patients and analysed separately for those previously on prophylaxis (P), situational prophylaxis (SP) or on-demand (OD).
Results Sixteen patients previously on P, 10 on SP and 10 on OD were enrolled in the study. The median (lower, upper quartile) ABJR changed from 2.0 (0, 4.0) to 0 (0, 1.6) for P (p = 0.003), from 2.0 (2.0, 13.6) to 3.0 (1.4, 7.2) for SP (p = 0.183) and from 16.0 (13.0, 25.0) to 2.3 (0, 5.0) for OD (p = 0.003). The Haemo-QoL-A total score improved for 58% of P, 50% of SP and 29% of OD patients. Factor utilization (IU/kg/patient/year) increased by 2,400 (121; 2,586) for P, 1,052 (308; 1,578) for SP and 2,086 (1,498; 2,576) for OD. One of 138 measurements demonstrated a factor activity level below the critical threshold of 0.03 IU/mL while the predicted level was above the threshold.
Conclusion Implementing tailored prophylaxis using a Bayesian forecasting approach in a routine clinical practice setting may improve haemophilia clinical outcomes.
Incidence of Cancer after a Second Unprovoked Venous Thromboembolic Event
Authors: Rézig Shéhérazade , Mao Raphael , Couturaud Francis , Lacut Karine , Delluc Aurélien 
Published: January 2019

AbstractPatients with two unprovoked venous thromboembolism (VTE) events could be at high risk for cancer diagnosis and may therefore benefit from extended cancer screening strategies. However, accurate data on the incidence of cancer in this population is lacking. In a prospective cohort study, we followed-up with all patients who experienced two unprovoked symptomatic VTE events that occurred in less than 2 years apart. We estimated the 1-year incidence rate of cancer following the second unprovoked VTE event using the Kaplan–Meier method. Potential predictors for cancer diagnosis were assessed using a Cox proportional hazard regression model. Between May 2000 and December 2013, we included 197 patients with two episodes of symptomatic unprovoked VTE that occurred in less than 2 years apart. Their mean age was 66.2 ± 16.3 years, and 122 (51.8%) were male. Seventeen patients were diagnosed with cancer during the year following the second episode of unprovoked VTE, corresponding to a cumulative incidence rate of 9.19% (95% confidence interval [CI]: 5.81–14.37). The 1-year cumulative incidence rate of cancer was 35.88% (95% CI: 19.75–59.25) in patients with VTE recurrence on anticoagulation, 5.51% (95% CI: 2.9–10.32) among patients with a second episode of unprovoked VTE occurring after stopping anticoagulation and 1.15% (95% CI: 0.16–7.88) when time elapsed between the first and recurrent VTE was > 1 year. Our study suggests that the incidence of cancer in patients with a second episode of unprovoked VTE that occurs off anticoagulation, or > 1 year after the first event, is similar to that of patients with a first unprovoked VTE event.
Using Cervical Dilation to Predict Labor Onset: A Tool for Elective Labor Induction Counseling
Authors: Panelli Danielle M. , Robinson Julian N. , Kaimal Anjali J. , Terry Kathryn L. , Yang Jiaxi , Clapp Mark A. , Little Sarah E. 
Published: January 2019

Objective To evaluate whether cervical dilation predicts the timing and likelihood of spontaneous labor at term.
Study Design This was a retrospective cohort of nulliparous women with singleton pregnancies who delivered at term from 2013 to 2015. Outpatient cervical examinations performed after 37 weeks and prior to labor onset were collected. Survival analysis was used to analyze time to spontaneous labor with cervical dilation as the primary predictor, modeled as continuous and categorical variables (<1 cm, 1 cm, >1 cm).
Results Our cohort included 726 women; 407 (56%) spontaneously labored, 263 (36%) were induced, and 56 (8%) had an unlabored cesarean delivery. Women with >1-cm dilation were three times more likely to spontaneously labor (adjusted hazard ratio [aHR]: 3.1; 95% confidence interval [CI]: 2.4–4) than those with <1-cm dilation. At 39 weeks, 60% of women with >1-cm dilation went into spontaneous labor as compared with only 28% of those with <1-cm dilation (aHR: 2.9; 95% CI: 2–4.4).
Conclusion In our cohort of nulliparous women at term, those with cervical dilation > 1 cm were significantly more likely to go into labor in the following week. This information can aid in counseling about elective induction of labor.
The Persistent Generalized Muscle Contraction in Siblings with Molybdenum Cofactor Deficiency Type A
Authors: Kibe Tetsuya , Hasegawa Hiroshi , Ichida Kimiyoshi , Koshimizu Eriko , Miyatake Satoko , Matsumoto Naomichi , Yokochi Kenji , Yoshimura Ayumi 
Published: January 2019

AbstractMolybdenum cofactor deficiency (MoCD) is a rare autosomal recessive metabolic disease with severe neurological symptoms. Most disease-causing mutations are found in the MOCS1 gene, corresponding to MoCD type A (MoCD-A). There have been few reports describing the long-term detailed neurological features with MoCD-A because most patients do not survive childhood. We describe the clinical, radiologic, biochemical, and genetic data of two patients (female siblings aged 26 and 22 years) with MoCD-A. Both patients presented with feeding difficulties, neurological deterioration, and persistent generalized muscle contraction which can be easily confused with status dystonicus. Biochemical tests revealed low serum uric acid, elevated urinary sulfocysteine, and xanthine. Brain magnetic resonance imaging (MRI) revealed distinctive abnormalities in the bilateral caudate nucleus, putamen, globus pallidus, and cerebral white matter adjacent to the cortex. The thalamus was relatively unaffected. Genetic testing identified a novel homozygous variant in the MOCS1 gene (c.949C > T p.Arg317Cys). Biochemical results supported the hypothesis that this genetic variant is a pathological mutation. When there are symptoms of persistent generalized muscle contraction and characteristic MRI findings, MoCD should be considered as a differential diagnosis.
Effect of HCl cleaning on InSb–Al2O3 MOS capacitors
Authors: Vavasour Oliver J , Jefferies Richard , Walker Marc , Roberts Joseph W , Meakin Naomi R , Gammon Peter M , Chalker Paul R , Ashley Tim 
Published: January 2019

Abstract
In this work, the role of HCl treatments on InSb surfaces and InSb–Al2O3 dielectric interfaces is characterised. X-ray photoelectron spectroscopy measurements indicate that HCl diluted in and rinsed with isopropanol (IPA) results in a surface layer of InCl3 which is not present for similar HCl-water processes. Furthermore, this InCl3 layer desorbs from the surface between 200 °C and 250 °C. Metal–oxide–semiconductor capacitors were fabricated using atomic layer deposition of Al2O3 at 200 °C and 250 °C and the presence of InCl3 was associated with a +0.79 V flatband voltage shift. The desorption of the InCl3 layer at 250 °C reversed this shift but the increased process temperature resulted in increased interface-trapped charge (D
it) and hysteresis voltage (V

H
). This shift in flatband voltage, which does not affect other figures of merit, offers a promising route to manipulate the threshold voltage of MOS transistors, allowing enhancement-mode and depletion-mode devices to be fabricated in parallel.
Prevalence and Factors Associated With Fatigue in Patients With Inflammatory Bowel Disease: A Multicentre Study
Authors: Chavarría C , Casanova M J , Chaparro M , Barreiro-de Acosta M , Ezquiaga E , Bujanda L , Rivero M , Argüelles-Arias F , Martín-Arranz M D , Martínez-Montiel M P , Valls M , Ferreiro-Iglesias R , Llaó J , Moraleja-Yudego I , Casellas F , Antolín-Melero B , Cortés X , Plaza R , Pineda J R , Navarro-Llavat M , García-López S , Robledo-Andrés P , Marín-Jiménez I , García-Sánchez V , Merino O , Algaba A , Arribas-López M R , Banales J M , Castro B , Castro-Laria L , Honrubia R , Almela P , Gisbert J P 
Published: January 2019

Abstract

Background and Aims
The aims of this study were to determine the prevalence of fatigue in patients with inflammatory bowel disease [IBD], to identify the factors associated with fatigue and its severity, to assess the impact of fatigue on quality of life [QoL], and to evaluate the relationship between fatigue and sleep disorders.

Methods
This was a prospective multicentre study conducted at 22 Spanish centres. Consecutive patients followed at IBD Units were included. Fatigue was evaluated with the Fatigue Severity Scale [FSS] and the Fatigue Impact Scale [FIS]. Quality of life and sleep quality were assessed using the IBD Questionnaire-Short Form [IBDQ-9] and the Pittsburgh Sleep Quality Index [PSQI], respectively.

Results
A total of 544 consecutive adult IBD patients were included [50% women, mean age 44 years, 61% Crohn’s disease]. The prevalence of fatigue was 41% (95% confidence interval [CI] = 37–45%). The variables associated with an increased risk of fatigue were: anxiety [OR = 2.5, 95% CI = 1.6–3.7], depression [OR = 2.4, 95% CI = 1.4–3.8], presence of extraintestinal manifestations [EIMs] [OR = 1.7, 95% CI = 1.1–2.6], and treatment with systemic steroids [OR = 2.8, 95% CI = 1.4–5.7]. The presence of EIMs [regression coefficient, RC = 8.2, 95% CI = 2.3–14.2], anxiety [RC = 25.8, 95% CI = 20.0–31.5], depression [RC = 30.6, 95% CI = 24.3–37.0], and sleep disturbances [RC = 15.0, 95% CI = 9.3–20.8] were associated with severity of fatigue. Patients with fatigue had a significantly decreased IBDQ-9 score [p < 0.001].

Conclusions
The prevalence of fatigue in IBD patients is remarkably high and has a negative impact on QoL. Therapy with systemic steroids is associated with an increased risk of fatigue. The severity of fatigue is associated with anxiety, depression, sleep disorders, and the presence of EIMs. Fatigue was not associated with anaemia, disease activity or anti-TNF therapy.
Health Professional Perspectives on Rehabilitation for People With Dementia
Authors: Cations Monica , May Natalie , Crotty Maria , Low Lee-Fay , Clemson Lindy , Whitehead Craig , McLoughlin James , Swaffer Kate , Laver Kate E 
Published: January 2019

Abstract

Background and Objectives
Multidisciplinary rehabilitation is not incorporated into the usual care pathway for dementia despite increasing demand from key advocates. Clinician views regarding the relevance of rehabilitation in dementia care are not well known. This qualitative study explored the perspectives of health professionals regarding barriers to provision of multidisciplinary rehabilitation programs for people with dementia.

Research Design and Methods
Sixteen health professionals from a variety of settings and professional backgrounds were purposively sampled using maximum variation sampling. Semi-structured interviews were conducted to explore attitudes toward the care of people with dementia and beliefs about the feasibility and value of multidisciplinary rehabilitation in this population. Thematic analysis was used to identify themes.

Results
Participating clinicians acknowledged problems with existing dementia care pathways in Australia but rarely conceptualized rehabilitation as relevant to this pathway. Analyses yielded two main and related themes: (i) difficulty defining worthwhile outcomes of a rehabilitation program for people with dementia and (ii) perceived barriers to participation in this population. Clinicians felt that achievable outcomes for people with dementia were not sufficiently worthwhile for investment.

Discussion and Implications
Broader acceptance of multidisciplinary rehabilitation as relevant to dementia care will require a reframing of practice that both educates emerging health professionals regarding the outcomes that may be achievable for people with dementia and persuades staff to appreciate that the investment is worthwhile.
On the Inhomogeneity of the Mandelbrot Set
Authors: Luo Yusheng 
Published: January 2019

Abstract
We will show that the Mandelbrot set $M$ is locally conformally inhomogeneous; the only conformal map $f$ defined in an open set $U$ intersecting $\partial M$ and satisfying $f(U\cap \partial M)=f(U)\cap \partial M$ is the identity map. The proof uses the study of local conformal symmetries of the Julia sets of polynomials; we will show in many cases that the dynamics can be recovered from the local conformal structure of the Julia sets.
Use of Aspergillus fumigatus real-time PCR in bronchoalveolar lavage samples (BAL) for diagnosis of invasive aspergillosis, including azole-resistant cases, in high risk haematology patients: the need for a combined use with galactomannan
Authors: Mikulska Malgorzata , Furfaro Elisa , De Carolis Elena , Drago Enrico , Pulzato Ilaria , Borghesi Maria Lucia , Zappulo Emanuela , Raiola Anna Maria , Grazia Carmen Di , Del Bono Valerio , Cittadini Giuseppe , Angelucci Emanuele , Sanguinetti Maurizio , Viscoli Claudio 
Published: January 2019

AbstractDiagnosis of invasive aspergillosis (IA) is challenging, particularly in high-risk patients with lung lesions other than typical according to 2008-EORTC/MSG criteria. Even if microbiology is positive, they still remain unclassified according to 2008-EORTC/MSG. Quantitative polymerase chain reaction (qPCR) provides new mycological documentation of IA. This retrospective study assessed Aspergillus fumigatus real time qPCR (MycoGENIE®) in BAL to diagnose IA and identify azole-resistant strains. Clinical, radiological, and microbiological data from 114 hematology patients (69% HSCT recipients; 29% on mould active agents) from years 2012-2017 were collected; and 123 BAL samples were tested with qPCR (cutoff: Ct < 40) and galactomannan (GM, Platelia®, cutoff: 0.5 ODI). Patients were classified as proven/probable, possible, and no-IA. "Atypical-IA" referred to patients with lesions other than typical according to 2008-EORTC/MSG and positive mycology. Proven IA was diagnosed in two cases (1.6%), probable in 28 (22.8%), possible in 27 (22%), atypical in 14 (11.4%). qPCR was positive in 39 samples (31.7%). Sensitivity and specificity of qPCR for proven/probable IA (vs no-IA; atypical-IA excluded) were 40% (95% confidence interval [CI]: 23–59) and 69% (95%CI: 55–81), respectively. Sensitivity of qPCR was higher when combined with GM (83%, 95%CI: 65–94) and in those receiving mould-active agents at BAL (61%, 95%CI: 32–86). One sample had TR34/L98H mutation. In conclusion, in high-risk hematology patients with various lung lesions, A. fumigatus qPCR in BAL contributes to diagnosing IA, particularly if combined with GM and in patients receiving mould-active agents might allow detecting azole-resistant mutations in culture negative samples.
Coping with selection effects: a Primer on regression with truncated data
Authors: Mantz Adam B 
Published: January 2019

Abstract
The finite sensitivity of instruments or detection methods means that data sets in many areas of astronomy, for example cosmological or exoplanet surveys, are necessarily systematically incomplete. Such data sets, where the population being investigated is of unknown size and only partially represented in the data, are called ‘truncated' in the statistical literature. Truncation can be accounted for through a relatively straightforward modification to the model being fitted in many circumstances, provided that the model can be extended to describe the population of undetected sources. Here, I examine the problem of regression using truncated data in general terms, and use a simple example to show the impact of selecting a subset of potential data on the dependent variable, on the independent variable, and on a second dependent variable that is correlated with the variable of interest. Special circumstances in which selection effects are ignorable are noted. I also comment on computational strategies for performing regression with truncated data, as an extension of methods that have become popular for the non-truncated case, and provide some general recommendations.
Contribution of Human Herpesvirus 8 and Herpes Simplex Type 2 to Progression of Carotid Intima-Media Thickness in People Living With HIV
Authors: Lidón Fernando , Padilla Sergio , García Jose A , Fernández Marta , García Javier , Ortiz de la Tabla Victoria , Gutiérrez Félix , Masiá Mar 
Published: January 2019

Abstract

Background
Human herpesvirus 8 (HHV-8) is a lymphotropic and vasculotropic herpesvirus with potential pro-atherogenic effects. We explored the influence of coinfection with HHV-8 and other herpesviruses on the rate of progression of carotid intima-media thickness (cIMT) in virologically suppressed people living with HIV (PLWH).

Methods
Prospective cohort study including men who have sex with men (MSM) infected with HIV. At the baseline visit, IgG antibodies against HHV-8 and other herpesviruses, highly sensitive C-reactive protein (hsCRP) levels, and Framingham risk scores were measured. To evaluate the progression of cIMT, successive measurements with high-resolution carotid artery ultrasound were performed over an 8-year period. Adjusted general linear mixed models were used to assess factors associated with faster cIMT progression.

Results
One hundred forty-one participants with suppressed HIV-RNA (&lt;200 copies/mL) at cIMT measurement during the study period were included. Forty-six (31.3%) were coinfected with HHV-8 and 76 (54%) with herpes simplex virus 2 (HSV-2). Factors associated with faster cIMT progression adjusting for CD4 cell counts, time between cIMT measurements, hepatitis C, varicella zoster virus, and cytomegalovirus coinfection were seropositivity for HHV-8 (P = .059), HSV-2+HHV-8 coinfection (P = .027), Framingham risk score (P = .057), and hsCRP (P = .027). Coinfection with HHV-8 was independently associated with higher levels of hsCRP (odds ratio, 1.09; 95% confidence interval, 1.02 to 1.17; P = .016). When hsCRP and HHV-8 were simultaneously included in the adjusted model, the relationship of HHV-8 with cIMT progression was attenuated.

Conclusions
HHV-8 might contribute to progression of cIMT with a more prominent role when it coinfects with HHV-2 in virologically suppressed PLWH, and this effect could be driven by systemic inflammation.
Is it possible to overcome the ‘long arm’ of childhood socioeconomic disadvantage through upward socioeconomic mobility?
Authors: Vable Anusha M , Gilsanz Paola , Kawachi Ichiro 
Published: January 2019

Abstract

Objectives
Socioeconomically disadvantaged children have worse adult health; we test if this ‘long arm’ of childhood disadvantage can be overcome through upward socioeconomic mobility in adulthood.

Methods
Four SES trajectories (stable low, upwardly mobile, downwardly mobile and stable high) were created from median dichotomized childhood socioeconomic status (SES; childhood human and financial capital) and adult SES (wealth at age 67) from Health and Retirement Study respondents (N = 6669). Healthy ageing markers, in tertiles, were walking speed, peak expiratory flow (PEF), and grip strength measured in 2008 and 2010. Multinomial logistic regression models, weighted to be nationally representative, controlled for age, gender, race, birthplace, outcome year and childhood health and social capital.

Results
Upwardly mobile individuals were as likely as the stable high SES group to be in the best health tertile for walking speed (OR = 0.81; 95% CI: 0.63, 1.05; P = 0.114), PEF (OR = 0.97; 95% CI: 0.78, 1.21; P = 0.810) and grip strength (OR = 0.97; 95%CI: 0.74, 1.27; P = 0.980).

Discussion
Findings suggest the ‘long arm’ of childhood socioeconomic disadvantage can be overcome for these markers of healthy ageing through upward socioeconomic mobility.
Developing a graduate training program in Synthetic Biology: SynBioCDT
Authors: Cazimoglu Idil , Darlington Alexander P S , Grigonyte Aurelija , Hoskin Charlotte E G , Liu Juntai , Oppenheimer Robert , Siller-Farfán Jesús A , Grierson Claire , Papachristodoulou Antonis 
Published: January 2019

Abstract
This article presents the experience of a team of students and academics in developing a post-graduate training program in the new field of Synthetic Biology. Our Centre for Doctoral Training in Synthetic Biology (SynBioCDT) is an initiative funded by the United Kingdom’s Research Councils of Engineering and Physical Sciences (EPSRC), and Biotechnology and Biological Sciences (BBSRC). SynBioCDT is a collaboration between the Universities of Oxford, Bristol and Warwick, and has been successfully running since 2014, training 78 students in this field. In this work, we discuss the organization of the taught, research and career development training. We also address the challenges faced when offering an interdisciplinary program. The article concludes with future directions to continue the development of the SynBioCDT.
Anterior nucleus of paraventricular thalamus mediates chronic mechanical hyperalgesia
Authors: Chang Ya-Ting , Chen Wei-Hsin , Shih Hsi-Chien , Min Ming-Yuan , Shyu Bai-Chuang , Chen Chien-Chang 
Published: January 2019

Abstract
Pain-related diseases are the top leading causes of life disability. Identifying brain regions involved in persistent neuronal changes will provide new insights for developing efficient chronic pain treatment. Here, we showed that anterior nucleus of paraventricular thalamus (PVA) plays an essential role in the development of mechanical hyperalgesia in neuropathic and inflammatory pain models in mice. Increase in c-Fos, phosphorylated extracellular signal–regulated kinase, and hyperexcitability of PVA neurons were detected in hyperalgesic mice. Direct activation of PVA neurons using optogenetics and pharmacological approaches were sufficient to induce persistent mechanical hyperalgesia in naive animals. Conversely, inhibition of PVA neuronal activity using DREADDs (designer receptors exclusively activated by designer drugs) or inactivation of PVA extracellular signal–regulated kinase at the critical time window blunted mechanical hyperalgesia in chronic pain models. At the circuitry level, PVA received innervation from central nucleus of amygdala, a known pain-associated locus. As a result, activation of right central nucleus of amygdala with blue light was enough to induce persistent mechanical hyperalgesia. These findings support the idea that targeting PVA can be a potential therapeutic strategy for pain relief.