bluuebunny/crossref_metadata_2025_split huggingface dataset:
Circulating Beta-2 Microglobulin and Risk of Cancer: The Atherosclerosis Risk in Communities Study (ARIC)
Authors: Prizment Anna E. , Linabery Amy M. , Lutsey Pamela L. , Selvin Elizabeth , Nelson Heather H. , Folsom Aaron R. , Church Timothy R. , Drake Charles G. , Platz Elizabeth A. , Joshu Corinne 
Published: February 2016

AbstractBackground: Serum β-2 microglobulin (B2M), a major histocompatibility complex class I molecule that is a biomarker of kidney filtration and increased cell turnover, is elevated at the time of diagnosis in hematological and some solid cancers. However, serum B2M was not examined prospectively as a marker for cancer risk. We hypothesized that in a population without a prior cancer diagnosis, serum B2M is associated with risk of cancer (n = 2,436), including colorectal (n = 255), lung (n = 298), breast (n = 424), and prostate (n = 524) cancers, and hematological (n = 176) malignancies.Methods: The analytical cohort (n = 12,300) was followed for incident cancers from 1990 through 2006. B2M (range, 0.9–57.8 mg/L) was measured in stored serum collected in 1990–1992. Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals for cancer incidence and mortality in relation to quartiles of B2M.Results: Adjusting for age, sex, race, center, education, body mass index, smoking, aspirin, and hormone therapy (in women) and comparing highest to lowest B2M quartiles, HRs were 1.25 (1.06–1.47; Ptrend = 0.002) for total cancer risk and 2.21 (1.32–3.70; Ptrend=0.001) for colorectal cancer risk, with similar HRs for colon and rectal cancers. These associations remained after adjustment for an inflammatory biomarker, C-reactive protein, and after excluding the first three years of follow-up. Significant associations were also observed for mortality from total, lung, and hematological cancers.Conclusions: These findings provide the first evidence that higher serum B2M is associated with increased colorectal cancer risk.Impact: This study supports B2M as a potential biomarker for colorectal cancer risk. Cancer Epidemiol Biomarkers Prev; 25(4); 657–64. ©2016 AACR.
A Multi-Institution Phase I Trial of Ruxolitinib in Patients with Chronic Myelomonocytic Leukemia (CMML)
Authors: Padron Eric , Dezern Amy , Andrade-Campos Marcio , Vaddi Kris , Scherle Peggy , Zhang Qing , Ma Yan , Balasis Maria E. , Tinsley Sara , Ramadan Hanadi , Zimmerman Cassandra , Steensma David P. , Roboz Gail J. , Lancet Jeffrey E. , List Alan F. , Sekeres Mikkael A. , Komrokji Rami S. 
Published: February 2016

Abstract
Purpose: To conduct a phase I clinical trial exploring the safety and efficacy of ruxolitinib, a JAK1/2 inhibitor, for chronic myelomonocytic leukemia (CMML).
Experimental Design: Patients with CMML-1 were included without regard to previous therapy. Key exclusion criteria included an absolute neutrophil count (ANC) &lt;0.25 × 103 cells/dL and a platelet count &lt;35 × 103 cells/dL. Four cohorts were enrolled using a “rolling six” study design, with doses ranging from 5 to 20 mg twice daily of ruxolitinib in 5-mg dose escalations.
Results: Between March 2013 and January 2015, 20 patients were enrolled and treated with ruxolitinib. Seventy percent of patients had the proliferative subtype and 47% had higher risk disease by the Global MD Anderson Scoring System. Eight patients (42%) received a prior hypomethylating agent. No dose-limiting toxicities for ruxolitinib were identified. One subject had grade (G)3 thrombocytopenia with no other drug-associated G3 or G4 adverse events. The mean duration of therapy was 122 days (range, 28–409 days). Four had hematologic improvement and one patient had a partial response per 2006 International Working Group (IWG) criteria. Five of 9 patients with splenomegaly had a reduction in spleen size. Ten of 11 patients with reported disease-related symptoms had clinically meaningful or complete resolution. When combining IWG and spleen responses, a total response rate of 35% (n = 7) was identified. Correlative analysis demonstrated a reduction in inflammatory cytokines and GM-CSF–dependent STAT5 phosphorylation.
Conclusions: The recommended phase II dose of ruxolitinib is 20 mg twice daily. We demonstrate that ruxolitinib has promising activity in CMML with particular benefit in those with disease-related B symptoms that warrants further study. Clin Cancer Res; 22(15); 3746–54. ©2016 AACR.
See related commentary by Solary, p. 3707
Interaction of Insulin Resistance and Related Genetic Variants With Triglyceride-Associated Genetic Variants
Authors: Klimentidis Yann C. , Arora Amit 
Published: February 2016

Background—
Several studies suggest that some triglyceride-associated single-nucleotide polymorphisms (SNPs) have pleiotropic and opposite effects on glycemic traits. This potentially implicates them in pathways such as de novo lipogenesis, which is presumably upregulated in the context of insulin resistance. We therefore tested whether the association of triglyceride-associated SNPs with triglyceride levels differs according to one’s level of insulin resistance.

Methods and Results—

In 3 cohort studies (combined n=12 487), we tested the interaction of established triglyceride-associated SNPs (individually and collectively) with several traits related to insulin resistance, on triglyceride levels. We also tested the interaction of triglyceride SNPs with fasting insulin–associated SNPs, individually and collectively, on triglyceride levels. We find significant interactions of a weighted genetic risk score for triglycerides with insulin resistance on triglyceride levels (
P
interaction
=2.73×10
−11
and
P
interaction
=2.48×10
–11
for fasting insulin and homeostasis model assessment of insulin resistance, respectively). The association of the triglyceride genetic risk score with triglyceride levels is >60% stronger among those in the highest tertile of homeostasis model assessment of insulin resistance compared with those in the lowest tertile. Individual SNPs contributing to this trend include those in/near
GCKR
,
CILP2
, and
IRS1
, whereas
PIGV-NROB2
and
LRPAP1
display an opposite trend of interaction. In the pooled data set, we also identify a SNP–by–SNP interaction involving a triglyceride-associated SNP, rs4722551 near
MIR148A
, with a fasting insulin–associated SNP, rs4865796 in
ARL15
(
P
interaction
=4.1×10
−5
).

Conclusions—
Our findings may thus provide genetic evidence for the upregulation of triglyceride levels in insulin-resistant individuals, in addition to identifying specific genetic loci and a SNP–by–SNP interaction implicated in this process.
Impact of Prosthesis‐Patient Mismatch on Left Ventricular Myocardial Mechanics After Transcatheter Aortic Valve Replacement
Authors: Poulin Frédéric , Yingchoncharoen Teerapat , Wilson William M. , Horlick Eric M. , Généreux Philippe , Tuzcu E. Murat , Stewart William , Osten Mark D. , Woo Anna , Thavendiranathan Paaladinesh 
Published: February 2016

Background

The aim of this study was to compare left ventricular (
LV
) remodeling using myocardial strain between patients with severe aortic stenosis (
AS
) treated with transcatheter aortic valve replacement (
TAVR
) with and without prosthesis‐patient mismatch (
PPM
).

Methods and Results

In a retrospective study, speckle‐tracking echocardiography was used to measure global longitudinal strain (
GLS
) and strain rate (
GLSR
), circumferential strain, and rotation before and at mid‐term follow‐up post‐
TAVR
. Moderate and severe
PPM
were defined as an effective orifice area ≤0.85 and <0.65 cm
2
/m
2
, respectively. A total of 102 patients (median age, 83 years [77–88]) with severe
AS
were included. At 6±3 months post‐
TAVR
, moderate and severe
PPM
were found in 32 (31%) and 9 (9%) patients. Patients without
PPM
had a significant regression in
LV
mass (from 134±41 to 119±38 g/m
2
;
P
=0.001) at follow‐up whereas those with
PPM
did not. There was a significant improvement in
LV GLS
(−12.8±4.0 to −14.3±4.3%;
P
=0.01),
GLSR
(−0.61±0.20 to −0.73±0.25 second
−1
;
P
<0.001), and early diastolic strain rate (0.52±0.20 to 0.64±0.20 second
−1
;
P
<0.001) in patients without
PPM
, but not in those with
PPM
. After adjustment for pre‐
TAVR
ejection fraction and post‐
TAVR
aortic regurgitation, patients without
PPM
had greater improvement in
LV
longitudinal strain parameters compared to those with
PPM
. After a median follow‐up of 46.1 months (interquartile range, 35.4–60.8), there was no difference in survival between patients with and without
PPM
.

Conclusions

TAVR
was associated with an incidence of
PPM
of 40%. Greater reverse
LV
remodeling using myocardial strain was evident in patients without
PPM
compared to
PPM
. Presence of
PPM
was not associated with mortality.
“El Niño Like” Hydroclimate Responses to Last Millennium Volcanic Eruptions
Authors: Stevenson Samantha , Otto-Bliesner Bette , Fasullo John , Brady Esther 
Published: February 2016

Abstract
The hydroclimate response to volcanic eruptions depends both on volcanically induced changes to the hydrologic cycle and on teleconnections with the El Niño–Southern Oscillation (ENSO), complicating the interpretation of offsets between proxy reconstructions and model output. Here, these effects are separated, using the Community Earth System Model Last Millennium Ensemble (CESM-LME), by examination of ensemble realizations with distinct posteruption ENSO responses. Hydroclimate anomalies in monsoon Asia and the western United States resemble the El Niño teleconnection pattern after “Tropical” and “Northern” eruptions, even when ENSO-neutral conditions are present. This pattern results from Northern Hemisphere (NH) surface cooling, which shifts the intertropical convergence zone equatorward, intensifies the NH subtropical jet, and suppresses the Southeast Asian monsoon. El Niño events following an eruption can then intensify the ENSO-neutral hydroclimate signature, and El Niño probability is enhanced two boreal winters following all eruption types. Additionally, the eruption-year ENSO response to eruptions is hemispherically dependent: the winter following a Northern eruption tends toward El Niño, while Southern volcanoes enhance the probability of La Niña events and Tropical eruptions have a very slight cooling effect. Overall, eruption-year hydroclimate anomalies in CESM disagree with the proxy record in both Southeast Asia and North America, suggesting that model monsoon representation cannot be solely responsible. Possible explanations include issues with the model ENSO response, the spatial or temporal structure of volcanic aerosol distribution, or data uncertainties.
A Comparison of the Use and Quality of Antidiabetic Medication Regimens Between Non-Hispanic Black and White Adults With Uncontrolled Type 2 Diabetes in the US
Authors: Perez Alexandra , Elrod Shara , Sanchez Jesus 
Published: February 2016

Purpose The purpose of this study was to determine the use of clinical guideline–recommended antidiabetic therapies among whites and blacks with uncontrolled type 2 diabetes. Methods A secondary data analysis based on NHANES 2003-2012 cohort data including non-Hispanic black and white adults with uncontrolled (A1C ≥6.5%) type 2 diabetes. Results Blacks were more likely to have the highest levels of A1C compared to whites (A1C >9% = 29.8% vs 16.2%). There was no statistical difference in the use of recommended regimens across racial group (blacks 60.5% vs whites 66.0%). Blacks and whites who were most uncontrolled were least likely to be on recommended regimens (A1C 6.5%-7.4%: 78.5%, A1C 7.5%-9%: 57.2%; and A1C >9%: 54.1%). This pattern was most pronounced among blacks compared to whites but was not statistically different. Use of recommended therapies decreased 29.0 percentage points for blacks and 20.1 percentage points among whites from an A1C level of 6.5% to 7.4% to >9%, respectively. The total proportion of blacks and whites on intensified non-insulin triple or insulin-based therapies were 38.9% and 41.8%, respectively. Conclusions Even though blacks were more likely than whites to have the highest A1C, no significant differences were found in the use of clinical–guideline recommended regimens or other regimen use outcomes. Along with lifestyle modification, further intensification of antidiabetic regimens may help improve glycemic control and other disparities between blacks and whites.
Description of load progression and pain response during progressive resistance training early after total hip arthroplasty: secondary analyses from a randomized controlled trial
Authors: Mikkelsen Lone R , Petersen Annemette K , Mechlenburg Inger , Mikkelsen Søren , Søballe Kjeld , Bandholm Thomas 
Published: February 2016

Objective: To describe a progressive resistance training intervention implemented shortly after total hip arthroplasty, including a detailed description of load progression, pain response and adverse events to the training. Design: Secondary analyses of data from the intervention group in a randomized controlled trial. Subjects: This study reports data from the intervention group ( n = 37). Interventions: The protocol described supervised progressive resistance training of the operated leg two days/week in addition to home-based exercise five days/week and for 10 weeks. The relative load progressed from 12 repetition maximum to 8 repetition maximum during 10 weeks for the exercises: knee extension, hip abduction, -flexion and -extension. Main measures: Training load in kilograms (kg) for each exercise, hip pain during, before and after exercise using the Visual Analog Scale and adverse events during the initial four weeks of training. Results: The majority of patients experienced only moderate hip pain during exercise (range in median across exercises and sessions: 5–35 mm Visual Analog Scale) and mild pain at rest (median: 1–18 mm Visual Analog Scale), both of which decreased over time ( p < 0.001), despite a substantial increase in absolute training load (67%–166 % across exercises, p < 0.001). Out of 152 training sessions, short term pain response (an increase >20 mm Visual Analog Scale) occurred in 13 patients in 24 training sessions. Conclusion: Progressive resistance training as described in the present study can be implemented shortly following total hip arthroplasty with substantial load progression and no overall exacerbation of postoperative pain. Some patients may experience a short term pain response. Trial Registration (primary trial): NCT01214954
A study of the psychometric properties of 12-item World Health Organization Disability Assessment Schedule 2.0 in a large population of people with chronic musculoskeletal pain
Authors: Saltychev Mikhail , Bärlund Esa , Mattie Ryan , McCormick Zachary , Paltamaa Jaana , Laimi Katri 
Published: February 2016

Objective: To assess the validity of the Finnish translation of the 12-item World Health Organization Disability Assessment Schedule (WHODAS 2.0). Design: Cross-sectional cohort survey study. Setting: Physical and Rehabilitation Medicine outpatient university clinic. Subjects: The 501 consecutive patients with chronic musculoskeletal pain. Main measures: Exploratory factor analysis and a graded response model using item response theory analysis were used to assess the constructs and discrimination ability of WHODAS 2.0. Results: The exploratory factor analysis revealed two retained factors with eigenvalues 5.15 and 1.04. Discrimination ability of all items was high or perfect, varying from 1.2 to 2.5. The difficulty levels of seven out of 12 items were shifted towards the elevated disability level. As a result, the entire test characteristic curve showed a shift towards higher levels of disability, placing it at the point of disability level of +1 (where 0 indicates the average level of disability within the sample). Conclusions: The present data indicate that the Finnish translation of the 12-item WHODAS 2.0 is a valid instrument for measuring restrictions of activity and participation among patients with chronic musculoskeletal pain.
‘I think you just learnt as you went along’ – community clergy’s experiences of and attitudes towards caring for dying people: A pilot study
Authors: Goodhead Andrew , Speck Peter , Selman Lucy 
Published: February 2016

Background: Spiritual distress is a factor associated with poor outcomes at the end of life. Timely interventions, assessing and meeting spiritual distress, among patients are contained within nationally agreed guidance. Community clergy are well placed to work alongside healthcare professionals and chaplains to meet spiritual needs. Methods: Qualitative interviews among Christian clergy in two South East London boroughs and a self-completed Death Anxiety Questionnaire. Results: Fourteen clergy were interviewed from six Christian denominations. Participants described their experiences of ordination training and how helpful this had been for their work among Christian communities. Respondents were invited to discuss their knowledge of and involvement with palliative care services. Each interviewee also accounted for their understanding of pastoral care and spiritual care and considered whether any differences existed between these terms and, if so, what they were. Overall, clergy lacked any detailed formal training and had little experience of working with or relating to palliative care providers. Recommendations are made to improve educational opportunities and working relationships. Conclusions: Creating opportunities for clergy and palliative care staff to meet and undertake shared training will enhance the quality and level of care for people dying at home who wish to receive spiritual support. Enabling clergy to develop links with local palliative care centres will enhance confidence for both clergy and staff.
Subclinical pulmonary abnormalities in childhood-onset systemic lupus erythematosus patients
Authors: Veiga C S , Coutinho D S , Nakaie C M A , Campos L M A , Suzuki L , Cunha M T , Leone C , Silva C A , Rodrigues J C 
Published: February 2016

Objective The aims of this study were to analyze the pulmonary function of childhood-onset systemic lupus erythematosus (cSLE) patients and to identify possible correlations between the high-resolution computed chest tomography (HRCT) score, disease activity, disease cumulative damage, and the participants’ quality of life. Methods Forty cSLE patients, median age: 14.1 years (range: 7.4–17.9), underwent spirometry and plethysmography. Carbon monoxide diffusing capacity (DLCO), HRCT, disease activity, disease cumulative damage, and quality of life were assessed. Results Pulmonary abnormalities were evident in 19/40 (47.5%) cSLE patients according to spirometry/DLCO. Forced expired volume in one second (FEV1%) was the parameter most affected (30%). The HRCT showed some abnormality in 22/30 patients (73%), which were minimal in 43%. Signs of airway affects were found in 50%. Twelve patients were hospitalized due to cSLE-related pulmonary complications before the study began (median discharge: 2.1 years earlier). Total lung capacity (TLC%), vital capacity (VC%), forced vital capacity (FVC%), and FEV1% were significantly lower in the group with hospitalization compared to the group without hospitalization ( p = 0.0025, p = 0.0022, p = 0.0032, and p = 0.0004, respectively). Of note, DLCO was positively correlated with disease duration ( r = +0.4; p = 0.01). The HRCT-score was negatively correlated with FEV1/VC ( r = −0.63; p = 0.0002), FEV1 ( r = −0.54; p = 0.018), FEF25%–75% ( r = −0.67; p < 0.0001), and HRCT-score was positively correlated with resistance ( r = +0.49; p = 0.0056). Conclusions Almost half of patients with cSLE had subclinical pulmonary abnormalities, especially airway abnormalities. The cSLE-related pulmonary complications seem to determine long-term functional damage.
Should ketamine be used for the clinical treatment of depression?
Authors: Arunogiri Shalini , Keks Nicholas A , Hope Judy 
Published: February 2016

Objective: There has been widespread interest from the public and media in the potential of ketamine as a novel treatment for depression. This paper reviews whether current evidence supports the use of ketamine for the clinical treatment of depression. Conclusions: Clinical trials have investigated the use of intravenous ketamine for the treatment of depressive symptoms over the past 15 years. However, there remain many unanswered questions regarding its effectiveness, safety, and the route, dose and regimen for repeated administration. Experts have also raised concerns regarding ketamine’s adverse effects, abuse potential and the risk of addiction. At this stage, the use of ketamine in the treatment of depression remains in the realm of research settings.
Rate of community treatment orders and readmission orders following reconfiguration of community mental health services
Authors: O’Donoghue Brian , Brophy Lisa , Owens Nicholas , Rasic Milana , McCullough Belinda , Huang Beatrice , Vine Ruth , McKenna Brian 
Published: February 2016

Objectives: Community treatment orders (CTOs) are a controversial practice as they extend the practice of involuntary treatment into the community. This study aimed to determine whether there was a difference in the rate of CTOs and revocation (readmission) orders following the implementation of a recovery-orientated model across four adult mental health services. Methods: A retrospective cohort study was conducted prior to and after the reconfiguration of services. Population data for those aged 15 to 65 were obtained from a census and rate rates were calculated. Results: Prior to the reconfiguration, there were 893 individuals subject to a CTO and 136 of these individuals had a revocation of their CTO (i.e. were involuntarily readmitted). This represented a rate of 100.8 individuals on CTOs per 100,000 population and a rate of 15.4 revocations per 100,000 population. Following the reconfiguration, the rate of CTOs increased by 10% and there was a trend for the rate of revocation orders to have decreased by 17%. Conclusions: Rates of CTOs and readmissions varied across services and further research is warranted to identify factors associated with these increased rates. Additionally, the very high rate of CTOs in the catchment areas warrants further examination.
Building Better Digital Badges
Authors: McDaniel Rudy , Fanfarelli Joseph 
Published: February 2016

Background. Digital badges are used in games and simulations for purposes such as incentivizing learning, identifying progress, increasing time on task, and credentialing. Designing effective badges is complicated by psychological factors mediating the processes of recognizing, orienting toward, and acquiring badges. Aim. This article analyzes digital badges through mechanics and psychology. This approach involves understanding the underlying logics of badges as well as the experiential nature of badges-in-use. The proposed model provides additional insight about badges and recommends design strategies to complement existing scholarship. Procedure. This article examines an existing model of completion logic for digital badges. This model is expanded upon by pairing these formal mechanics with relevant psychological theory, summarizing key principles that pertain to how people interact with badges. It then considers three dimensions of badges-in-use—social, cognitive, and affective—reviewing examples and analyzing the relationship of badging to debriefing. Outcome. Understanding the relationships between formal completion logics and the psychological experience of badging allows designers to better design, deploy, and critique badging systems, leading to more effective implementations within simulation and gaming contexts. A design matrix and a series of design recommendations for badging are derived from the presented perspectives.