bluuebunny/crossref_metadata_2025 huggingface dataset:
A colimit of traces of reflection groups
Authors: Li Penghui
Published: February 2019

Li-Nadler proposed a conjecture about traces of Hecke categories, which implies the semistable part of the Betti geometric Langlands conjecture of Ben-Zvi-Nadler in genus 1. We prove a Weyl group analogue of this conjecture. Our theorem holds in the natural generality of reflection groups in Euclidean or hyperbolic space. As a corollary, we give an expression of the centralizer of a finite order element in a reflection group using homotopy theory.
Uniformly non–improvable Dirichlet set via continued fractions
Authors: Huang Lingling , Wu Jun
Published: February 2019

Let

[

a
1

(
x
)
,

a
2

(
x
)
,
…
]

[a_1(x),a_2(x),\ldots ]

be the continued fraction expansion of

x
∈
[
0
,
1
)

x\in [0,1)

and let

q
n

(
x
)

q_n(x)

be the denominator of the

n
n

th convergent. Recently, Hussain-Kleinbock-Wadleigh-Wang (2018) showed that for any

τ
≥
0
,

\tau \ge 0,

the set
<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" alttext="upper D Superscript c Baseline left-parenthesis tau right-parenthesis equals StartSet x element-of left-bracket 0 comma 1 right-parenthesis colon limit sup StartFraction log left-parenthesis a Subscript n Baseline left-parenthesis x right-parenthesis a Subscript n plus 1 Baseline left-parenthesis x right-parenthesis right-parenthesis Over log q Subscript n Baseline left-parenthesis x right-parenthesis EndFraction greater-than-or-equal-to tau EndSet">

D

c

(
τ
)
=

{

x
∈
[
0
,
1
)
:

lim sup

n
→
∞

log
⁡

(

a
n

(
x
)

a

n
+
1

(
x
)

)

log
⁡

q
n

(
x
)

≥
τ

}

\begin{equation*} D^{c}(\tau )=\Big \{x\in [0,1): \limsup \limits _{n\rightarrow \infty }\frac {\log \big (a_n(x)a_{n+1}(x)\big )}{\log q_n(x)}\ge \tau \Big \} \end{equation*}

is of Hausdorff dimension

2

τ
+
2

.

\frac {2}{\tau +2}.

In this note, we study the Hausdorff dimension of the set
<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" alttext="StartLayout 1st Row 1st Column Blank 2nd Column a m p semicolon upper F left-parenthesis tau right-parenthesis equals StartSet x element-of left-bracket 0 comma 1 right-parenthesis colon limit Underscript n right-arrow normal infinity Endscripts StartFraction log left-parenthesis a Subscript n Baseline left-parenthesis x right-parenthesis a Subscript n plus 1 Baseline left-parenthesis x right-parenthesis right-parenthesis Over log q Subscript n Baseline left-parenthesis x right-parenthesis EndFraction equals tau EndSet period EndLayout">

a
m
p
;
F
(
τ
)
=

{

x
∈
[
0
,
1
)
:

lim

n
→
∞

log
⁡

(

a
n

(
x
)

a

n
+
1

(
x
)

)

log
⁡

q
n

(
x
)

=
τ

}

.

\begin{align*} &F(\tau )=\Big \{x\in [0,1): \lim \limits _{n\rightarrow \infty }\frac {\log \big (a_n(x)a_{n+1}(x)\big )}{\log q_n(x)}=\tau \Big \}. \end{align*}

It is proved that the set

F
(
τ
)

F(\tau )

has Hausdorff dimension

1
1

or

2

τ
+

τ
2

+
4

+
2

\frac {2}{\tau +\sqrt {\tau ^2+4}+2}

according as

τ
=
0

\tau =0

or

τ
>
0.

\tau >0.
To What Extent Does Age at Death Account for Sex Differences in Rates of Mortality From Alzheimer Disease?
Authors: Buckley Rachel F , Waller Michael , Masters Colin L , Dobson Annette
Published: February 2019

Our objective was to compare sex-specific rates of death with Alzheimer disease (AD) or dementia as the underlying or associated cause of death using death records. Deidentified individual records on causes of death for all people aged 60 years or more who died in Australia during 2006–2014 (n = 1,104,684) were analyzed. There were 184,562 records with International Classification of Diseases, Tenth Revision, codes for dementia (AD, vascular dementia, or unspecified dementia). Death rate ratios for women versus men were estimated using Poisson regression. Women had a greater crude rate of death from all types of dementia than men (5.9 deaths per 1,000 person-years as compared with 3.8 deaths per 1,000 person-years), which disappeared after adjustment for age. For AD, the age-adjusted rate was higher among women (rate ratio = 1.14, 95% confidence interval: 1.12, 1.16), while for vascular dementia age-adjusted rates were higher for men (rate ratio = 0.80, 95% confidence interval: 0.78, 0.82). There was no evidence of a differential bias in coding of dementia type between men and women. Women’s older age at death explained much of the sex-related difference in rates of death from AD or dementia. However, excess numbers of AD deaths among women and vascular dementia deaths among men remained, providing support for the hypothesis of greater biological risk of AD in women.
Inflorescence shoot elongation, but not flower primordia formation, is photoperiodically regulated in Arabidopsis lyrata
Authors: Kemi Ulla , Leinonen Päivi H , Savolainen Outi , Kuittinen Helmi
Published: February 2019

Background and Aims

Photoperiod contains information about the progress of seasons. Plants use the changing photoperiod as a cue for the correct timing of important life history events, including flowering. Here the effect of photoperiod on flowering in four Arabidopsis lyrata populations originating from different latitudes was studied, as well as expression levels of candidate genes for governing the between-population differences.

Methods

Flowering of plants from four A. lyrata populations was studied in three different photoperiods after vernalization. Flowering development was separated into three steps: flower primordia formation, inflorescence shoot elongation and opening of the first flower. Circadian expression rhythms of the A. lyrata homologues of GIGANTEA (GI), FLAVIN-BINDING, KELCH REPEAT, F-BOX 1 (FKF1), CONSTANS (CO) and FLOWERING LOCUS T (FT) were studied in three of the populations in the intermediate (14 h) photoperiod treatment.

Key Results

Most plants in all populations formed visible flower primordia during vernalization. Further inflorescence development after vernalization was strongly inhibited by short days in the northern European population (latitude 61°N), only slightly in the central European population (49°N) and not at all in the North American populations (36°N and 42°N). In the 14 h daylength, where all plants from the three southernmost populations but only 60 % of the northernmost population flowered, the circadian expression rhythm of the A. lyrata FT was only detected in the southern populations, suggesting differentiation in the critical daylength for activation of the long-day pathway. However, circadian expression rhythms of A. lyrata GI, FKF1 and CO were similar between populations.

Conclusions

The results indicate that in A. lyrata, transition to flowering can occur through pathways independent of long days, but elongation of inflorescences is photoperiodically regulated.
BioMethyl: an R package for biological interpretation of DNA methylation data
Authors: Wang Yue , Franks Jennifer M , Whitfield Michael L , Cheng Chao
Published: February 2019

Motivation

The accumulation of publicly available DNA methylation datasets has resulted in the need for tools to interpret the specific cellular phenotypes in bulk tissue data. Current approaches use either single differentially methylated CpG sites or differentially methylated regions that map to genes. However, these approaches may introduce biases in downstream analyses of biological interpretation, because of the variability in gene length. There is a lack of approaches to interpret DNA methylation effectively. Therefore, we have developed computational models to provide biological interpretation of relevant gene sets using DNA methylation data in the context of The Cancer Genome Atlas.

Results

We illustrate that Biological interpretation of DNA Methylation (BioMethyl) utilizes the complete DNA methylation data for a given cancer type to reflect corresponding gene expression profiles and performs pathway enrichment analyses, providing unique biological insight. Using breast cancer as an example, BioMethyl shows high consistency in the identification of enriched biological pathways from DNA methylation data compared to the results calculated from RNA sequencing data. We find that 12 out of 14 pathways identified by BioMethyl are shared with those by using RNA-seq data, with a Jaccard score 0.8 for estrogen receptor (ER) positive samples. For ER negative samples, three pathways are shared in the two enrichments with a slight lower similarity (Jaccard score = 0.6). Using BioMethyl, we can successfully identify those hidden biological pathways in DNA methylation data when gene expression profile is lacking.

Availability and implementation

BioMethyl R package is freely available in the GitHub repository (https://github.com/yuewangpanda/BioMethyl).

Supplementary information

Supplementary data are available at Bioinformatics online.
Epidemiology, Risk Factors, and Outcomes of Respiratory Syncytial Virus Infections in Newborns in Bamako, Mali
Authors: Buchwald Andrea G , Tamboura Boubou , Tennant Sharon M , Haidara Fadima C , Coulibaly Flanon , Doumbia Moussa , Diallo Fatoumata , Keita Adama M , Sow Samba O , Kotloff Karen L , Levine Myron M , Tapia Milagritos D
Published: February 2019

Background

Few studies describe the respiratory syncytial virus (RSV) burden in African populations, and most have utilized hospital-based surveillance. In Mali, no community-based studies exist of the incidence or epidemiology of RSV infection. This study provides the first estimates of RSV incidence in Mali.

Methods

In a cohort of infants enrolled in a clinical trial of maternal influenza vaccination, we estimate incidence of RSV-associated febrile illness in the first 6 months of life and identify risk factors for RSV infection and progression to severe disease. Infants (N = 1871) were followed from birth to 6 months of age and visited weekly to detect pneumonia and influenza-like illness. Baseline covariates were explored as risk factors for RSV febrile illness and RSV pneumonia or hospitalization.

Results

Incidence of RSV illness was estimated at 536.8 per 1000 person-years, and 86% (131/153) of RSV illness episodes were positive for RSV-B. RSV illness was most frequent in the fifth month of life and associated with having older mothers and with lower parity. The incidence of RSV-associated hospitalizations was 45.6 per 1000 person-years. Among infants with RSV illness, males were more likely to be hospitalized. The incidence of RSV pneumonia was 29 cases per 1000 person-years.

Conclusions

In the first 6 months of life, Malian infants have a high incidence of RSV illness, primarily caused by RSV-B. Prevention of early RSV will require passive protection via maternal immunization in pregnancy. Mali is the first country where RSV-B has been identified as the dominant subtype, with potential implications for vaccine development.
Patterns of Hepatitis C Virus Transmission in Human Immunodeficiency Virus (HIV)–infected and HIV-negative Men Who Have Sex With Men
Authors: Ramière Christophe , Charre Caroline , Miailhes Patrick , Bailly François , Radenne Sylvie , Uhres Anne-Claire , Brochier Corinne , Godinot Matthieu , Chiarello Pierre , Pradat Pierre , Cotte Laurent ,   Lyon Acute Hepatitis Study Group, Astrie Marie , Augustin-Normand Claude , François Bailly , Biron François , Boibieux André , Brochier Corinne , Braun Evelyne , Brunel Florence , Charre Caroline , Chiarello Pierre , Chidiac Christian , Cotte Laurent , Ferry Tristan , Godinot Matthieu , Guillaud Olivier , Koffi Joseph , Livrozet Jean-Michel , Makhloufi Djamila , Miailhes Patrick , Perpoint Thomas , Pradat Pierre , Radenne Sylvie , Ramière Christophe , Schlienger Isabelle , Scholtes Caroline , Schuffenecker Isabelle , Tardy Jean-Claude , Trabaud Mary-Anne , Uhres Anne-Claire
Published: February 2019

Background

Sexually transmitted acute hepatitis C virus (HCV) infections (AHIs) have been mainly described in human immunodeficiency virus (HIV)–infected men who have sex with men (MSM). Cases in HIV-negative MSM are scarce. We describe the epidemic of AHI in HIV-infected and HIV-negative MSM in Lyon, France.

Methods

All cases of AHI diagnosed in MSM in Lyon University Hospital from 2014 to 2017 were included. AHI incidence was determined in HIV-infected and in preexposure prophylaxis (PrEP)–using MSM. Transmission clusters were identified by construction of phylogenetic trees based on HCV NS5B (genotype 1a/4d) or NS5A (genotype 3a) Sanger sequencing.

Results

From 2014 to 2017, 108 AHIs (80 first infections, 28 reinfections) were reported in 96 MSM (HIV-infected, 72; HIV-negative, 24). AHI incidence rose from 1.1/100 person-years (95 confidence interval [CI], 0.7–1.7) in 2014 to 2.4/100 person-years (95 CI, 1.1–2.6) in 2017 in HIV-infected MSM (P = .05) and from 0.3/100 person-years (95 CI, 0.06–1.0) in 2016 to 3.4/100 person-years (95 CI, 2.0–5.5) in 2017 in PrEP users (P < .001). Eleven clusters were identified. All clusters included HIV-infected MSM; 6 also included HIV-negative MSM. All clusters started with ≥1 HIV-infected MSM. Risk factor distribution varied among clusters.

Conclusions

AHI incidence increased in both HIV-infected and HIV-negative MSM. Cluster analysis suggests initial transmission from HIV-infected to HIV-negative MSM through chemsex and traumatic sexual practices, leading to mixed patterns of transmission regardless of HIV status and no overlap with the general population.
Sex Discrepancies in the Protective Effect of Opioid Agonist Therapy on Incident Hepatitis C Infection
Authors: Geddes Louise , Iversen Jenny , Wand Handan , Esmaeili Aryan , Tsui Judith , Hellard Margaret , Dore Gregory , Grebely Jason , Dietze Paul , Bruneau Julie , Prins Maria , Morris Megan D , Shoukry Naglaa H , Lloyd Andrew R , Kim Arthur Y , Lauer Georg , Cox Andrea L , Page Kimberly , Maher Lisa ,   International Collaboration of Incident HIV and HCV in Injecting Cohorts (InC3) Collaborative
Published: February 2019

Background

While opioid agonist therapy (OAT) reduces the risk of hepatitis C virus (HCV) acquisition among people who inject drugs (PWID), protective effects may be attenuated in females. We used pooled data from an international collaboration of prospective cohorts to assess sex disparities in HCV incidence among PWID exposed to OAT.

Methods

Independent predictors of HCV infection were identified using Cox regression models with random effects after accounting for the clustering effect of study sites. Unadjusted and adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) are presented in sex‐specific analyses.

Results

Among 701 participants exposed to OAT, HCV incidence was 16.5/100 person-years of observation (PYO) (95% CI, 13.1–20.7) in females and 7.6/100 PYO (95% CI, 6.0–9.5) in males (female:male adjusted HR [aHR], 1.80 [95% CI, 1.37–2.22]; P < .001). Factors associated with HCV acquisition among females exposed to OAT included nonwhite race (aHR, 1.79 [95% CI, 1.25–2.56]; P = .001), unstable housing (aHR, 4.00 [95% CI, 3.62–4.41]; P < .001), daily or more frequent injection (aHR, 1.45 [95% CI, 1.01–2.08]; P = .042), and receptive syringe sharing (aHR, 1.43 [95% CI, 1.33–1.53]; P < .001).

Conclusions

Female PWID exposed to OAT are twice as likely as their male counterparts to acquire HCV. While there is a need for better understanding of sex differences in immune function and opioid pharmacokinetic and pharmacodynamic parameters, structural and behavioral interventions that target women are required to bolster the efficacy of OAT in preventing HCV transmission.
Can Australia Reach the World Health Organization Hepatitis C Elimination Goal by 2025 Among Human Immunodeficiency Virus–positive Gay and Bisexual Men?
Authors: Boettiger David C , Salazar-Vizcaya Luisa , Dore Gregory J , Gray Richard T , Law Matthew G , Callander Denton , Lea Toby , Rauch Andri , Matthews Gail V
Published: February 2019

Background

Human immunodeficiency virus (HIV)–positive gay and bisexual men (GBM) in Australia are well engaged in care. The World Health Organization’s (WHO) hepatitis C virus (HCV) elimination target of an 80% reduction in incidence by 2030 may be reachable ahead of time in this population.

Methods

We predicted the effect of treatment and behavioral changes on HCV incidence among HIV-positive GBM up to 2025 using a HCV transmission model parameterized with Australian data. We assessed the impact of changes in behavior that facilitate HCV transmission in the context of different rates of direct-acting antiviral (DAA) use.

Results

HCV incidence in our model increased from 0.7 per 100 person-years in 2000 to 2.5 per 100 person-years in 2016 and had the same trajectory as previously reported clinical data. If the proportion of eligible (HCV RNA positive) patients using DAAs stays at 65% per year between 2016 and 2025, with high-risk sexual behavior and injecting drug use remaining at current levels, HCV incidence would drop to 0.4 per 100 person-years (85% decline from 2016). In the same treatment scenario but with substantial increases in risk behavior, HCV incidence would drop to 0.6 per 100 person-years (76% decline). If the proportion of eligible patients using DAAs dropped from 65% per year in 2016 to 20% per year in 2025 and risk behavior did not change, HCV incidence would drop to 0.7 per 100 person-years (70% reduction).

Conclusions

Reaching the WHO HCV elimination target by 2025 among HIV-positive GBM in Australia is achievable.
Cardiovascular disease burden from ambient air pollution in Europe reassessed using novel hazard ratio functions
Authors: Lelieveld Jos , Klingmüller Klaus , Pozzer Andrea , Pöschl Ulrich , Fnais Mohammed , Daiber Andreas , Münzel Thomas
Published: February 2019

Aims

Ambient air pollution is a major health risk, leading to respiratory and cardiovascular mortality. A recent Global Exposure Mortality Model, based on an unmatched number of cohort studies in many countries, provides new hazard ratio functions, calling for re-evaluation of the disease burden. Accordingly, we estimated excess cardiovascular mortality attributed to air pollution in Europe.

Methods and results

The new hazard ratio functions have been combined with ambient air pollution exposure data to estimate the impacts in Europe and the 28 countries of the European Union (EU-28). The annual excess mortality rate from ambient air pollution in Europe is 790 000 [95% confidence interval (95% CI) 645 000–934 000], and 659 000 (95% CI 537 000–775 000) in the EU-28. Between 40% and 80% are due to cardiovascular events, which dominate health outcomes. The upper limit includes events attributed to other non-communicable diseases, which are currently not specified. These estimates exceed recent analyses, such as the Global Burden of Disease for 2015, by more than a factor of two. We estimate that air pollution reduces the mean life expectancy in Europe by about 2.2 years with an annual, attributable per capita mortality rate in Europe of 133/100 000 per year.

Conclusion

We provide new data based on novel hazard ratio functions suggesting that the health impacts attributable to ambient air pollution in Europe are substantially higher than previously assumed, though subject to considerable uncertainty. Our results imply that replacing fossil fuels by clean, renewable energy sources could substantially reduce the loss of life expectancy from air pollution.
The Linkage Between Aging, Migration, and Resilience: Resilience in the Life of Older Turkish and Moroccan Immigrants
Authors: Klokgieters Silvia S , van Tilburg Theo G , Deeg Dorly J H , Huisman Martijn
Published: February 2019

Objectives

Older immigrants are affected by an accumulation of adversities related to migration and aging. This study investigates resilience in older immigrants by examining the resources they use to deal with these adversities in the course of their lives.

Methods

Data from 23 life-story interviews with Turkish and Moroccan immigrants aged 60–69 years living in the Netherlands.

Results

The circumstances under which individuals foster resilience coincide with four postmigration life stages: settling into the host society, maintaining settlement, restructuring life postretirement, and increasing dependency. Resources that promote resilience include education in the country of origin, dealing with language barriers, having two incomes, making life meaningful, strong social and community networks, and the ability to sustain a transnational lifestyle traveling back and forth to the country of origin. More resilient individuals invest in actively improving their life conditions and are good at accepting conditions that cannot be changed.

Discussion

The study illustrates a link between conditions across life stages, migration, and resilience. Resilient immigrants are better able to accumulate financial and social and other resources across life stages, whereas less resilient immigrants lose access to resources in different life stages.
A Cross-Sectional Study on Malnutrition in Inflammatory Bowel Disease: Is There a Difference Based on Pediatric or Adult Age Grouping?
Authors: Marcil Valérie , Levy Emile , Amre Devendra , Bitton Alain , Sant’Anna Ana Maria Guilhon de Araújo , Szilagy Andrew , Sinnett Daniel , Seidman Ernest G
Published: February 2019

Background

Malnutrition, commonly observed in inflammatory bowel disease (IBD), is associated with increased morbidity and mortality and is attributed to multiple causes. The added energy costs of growth in the child and adolescent with IBD are an additional risk factor.

Methods

The aim of the study was to perform a cross-sectional comparison of nutritional parameters in IBD between pediatric and adult cases.

Results

We found that prevalence of undernutrition (low body mass index) and hypoalbuminemia was not different in pediatric, compared with adult patients. Anemia and iron deficiency were more often observed in pediatric subjects, compared with adults (59.1% vs 36.9%, respectively, P < 0.0001; and 37.9% vs 25.3%, P < 0.002). Vitamin B12 deficiency was significantly less common in the pediatric than in the adult group (5.4% vs 19.4%, P < 0.0001). Elevated C-reactive protein was more frequent in pediatric compared with adult cases (49.8% vs 38.4%, P < 0.01).

Conclusions

Patients with active Crohn’s disease were more likely to be undernourished in both pediatric and adult populations. In both groups, predicators of undernutrition included low albumin levels (odds ratio [OR], 2.53; P < 0.006) and active disease (OR, 1.99; P < 0.03). Our results call for close surveillance of nutritional status for IBD patients, regardless of age.
Cannula position and Bernoulli effect contribute to leg malperfusion during extracorporeal life support with femoral arterial cannulation—an in silico simulation study
Authors: Bongert Markus , Gehron Johannes , Geller Marius , Böning Andreas , Grieshaber Philippe
Published: February 2019

OBJECTIVES

Limb ischaemia during extracorporeal life support (ECLS) using femoral artery cannulation is frequently observed even in patients with regular vessel diameters and without peripheral arterial occlusive disease. We investigated underlying pathomechanisms using a virtual fluid-mechanical simulation of the human circulation.

METHODS

A life-sized model of the human aorta and major vascular branches was virtualized using 3-dimensional segmentation software (Mimics, Materialise). Steady-state simulation of different grades of cardiac output (0–100%) was performed using Computational Fluid Dynamics (CFX, ANSYS). A straight cannula [virtualized 16 Fr (5.3 mm)] was inserted into the model via the left common femoral artery. The ECLS flow was varied between 1 and 5 l/min. The pressure boundary conditions at the arterial outlets were selected to demonstrate the downstream vascular system. Qualitative and quantitative analyses concerning flow velocity and direction were carried out in various regions of the model.

RESULTS

During all simulated stages of reduced cardiac output and subsequently adapted ECLS support, retrograde blood flow originating from the ECLS cannula was observed from the cannulation site up to the aortic bifurcation. Analysis of pressure showed induction of zones of negative pressure close to the cannula tip, consistent with the Bernoulli principle. Depending on cannula position and ECLS flow rate, this resulted in negative flow from the ipsilateral superficial femoral artery or the contralateral internal iliac artery. The antegrade flow to the non-cannulated side was generally greater than that to the cannulated side.

CONCLUSIONS

The cannula position and ECLS flow rate both influence lower limb perfusion during femoral ECLS. Therefore, efforts to optimize the cannula position and to avoid limb malperfusion, including placement of a distal perfusion cannula, should be undertaken in patients treated with ECLS.
Competition for Status Creates Superstars: an Experiment on Public Good Provision and Network Formation
Authors: van Leeuwen Boris , Offerman Theo , Schram Arthur
Published: February 2019

We investigate a mechanism that facilitates the provision of public goods in a network formation game. We show how competition for status encourages a core player to realize efficiency gains for the entire group. In a laboratory experiment we systematically examine the effects of group size and exogenously monetarized status rents. The experimental results provide very clear support for the concept of challenge-freeness, a refinement that predicts when a repeated game equilibrium will be played, and if so which one. Two control treatments allow us to reject the possibility that these observations are driven by social preferences, independently of the competition for status.
Assessing Long-Term Survival Benefits of Immune Checkpoint Inhibitors Using the Net Survival Benefit
Authors: Péron Julien , Lambert Alexandre , Munier Stephane , Ozenne Brice , Giai Joris , Roy Pascal , Dalle Stéphane , Machingura Abigirl , Maucort-Boulch Delphine , Buyse Marc
Published: February 2019

Background

The treatment effect in survival analysis is commonly quantified as the hazard ratio, and tested statistically using the standard log-rank test. Modern anticancer immunotherapies are successful in a proportion of patients who remain alive even after a long-term follow-up. This new phenomenon induces a nonproportionality of the underlying hazards of death.

Methods

The properties of the net survival benefit were illustrated using the dataset from a trial evaluating ipilimumab in metastatic melanoma. The net survival benefit was then investigated through simulated datasets under typical scenarios of proportional hazards, delayed treatment effect, and cure rate. The net survival benefit test was computed according to the value of the minimal survival difference considered clinically relevant. As comparators, the standard and the weighted log-rank tests were also performed.

Results

In the illustrative dataset, the net survival benefit favored ipilimumab [Δ(0) = 15.8%, 95% confidence interval = 4.6% to 27.3%, P = .006]. This favorable effect was maintained when the analysis was focused on long-term survival differences (eg, >12 months, Δ(12) = 12.5% (95% confidence interval = 4.4% to 20.6%, P = .002). Under the scenarios of a delayed treatment effect and cure rate, the power of the net survival benefit test compared favorably to the standard log-rank test power and was comparable to the power of the weighted log-rank test for large values of the threshold of clinical relevance.

Conclusion

The net long-term survival benefit is a measure of treatment effect that is meaningful whether or not hazards are proportional. The associated statistical test is more powerful than the standard log-rank test when a delayed treatment effect is anticipated.
Trends in International Incidence of Pediatric Cancers in Children Under 5 Years of Age: 1988–2012
Authors: Hubbard Aubrey K , Spector Logan G , Fortuna Giulio , Marcotte Erin L , Poynter Jenny N
Published: February 2019

Background

Pediatric cancer incidence has been steadily increasing over the last several decades with the largest increases reported in infants. Few evaluations have looked at international pediatric cancer incidence trends in the youngest children. The aim of this analysis was to evaluate trends in cancer incidence in children under 5 years of age, overall and by type, using data from Cancer Incidence in 5 Continents (CI5) from 1988 to 2012 (CI5 volumes VII–XI).

Methods

Rates of cancers in children ages 0–4 years were extracted from registries available in CI5 from 1988 to 2012. To overcome small numbers in individual registries, numerators and denominators were aggregated within regions corresponding to the United Nations’ geoscheme. Average annual percent change (AAPC) was estimated using Poisson regression.  Robust standard errors were used in all models to correct for overdispersion in some regions, and 95% Wald confidence intervals and P values were reported. The top five cancers by increasing AAPC were ranked within each region.

Results

Overall, in children under 5 years, increasing incidence was seen in multiple regions for acute lymphoblastic leukemia, acute myeloid leukemia, ependymal tumors, neuroblastoma, and hepatoblastoma. Hepatoblastoma had the largest AAPC in 11 out of 15 regions and showed an increase in all regions except southern Asia. Astrocytic tumors were the only cancer that decreased over the time period.

Conclusions

We evaluated 25 years of cancer incidence in children ages 0–4 years and observed increases in incidence for hepatoblastoma, leukemia, neuroblastoma, and ependymal tumors. Further etiologic evaluation will be required to explain these increases in incidence.
Psychodynamic Therapy Techniques
Authors: Sharpless Brian A.
Published: February 2019

Psychodynamic therapy is one of the most popular orientations practiced in the world today. The past few decades of research have also provided evidence for its clinical efficacy. However, gaining competence in this approach generally requires years of training and mastery of a large and complex literature. This easily accessible text focuses specifically on the techniques needed for contemporary psychodynamic practice. Written for the intermediate-beginner, it first teaches readers how to think and respond to patients in a consistent psychodynamic manner. Other early chapters focus on the characteristics of “good” interventions and ways to assess their clinical impacts. Next, the book provides straightforward guidance on how to question, clarify, confront, and interpret patient material. These “classic” techniques are then supplemented with six sets of supportive interventions helpful for lower-functioning patients or those in acute crisis. Finally, the procedures required to effectively resolve alliance ruptures are described along with suggestions for using these events to enact clinical gains. In addition to clear, step-by-step instructions on how to prepare techniques (e.g., interpretations), the author provides numerous clinical vignettes. Further, a supplemental appendix conveniently gathers the psychodynamic therapy models and treatment manuals that have been used in empirical studies. These may be helpful for researchers and other readers interested in pursuing more advanced training. Grounded in both sophisticated clinical theory and up-to-date research findings, this book effectively demystifies psychodynamic therapy techniques and helps practitioners more effectively apply them to a wide range of patients and problems.
The Psychodynamic “Stance”
Authors: Sharpless Brian A.
Published: February 2019

The psychodynamic stance (as known as the psychodynamic sensibility) is a collection of essential values and theoretical assumptions that support a therapist’s moment-to-moment practice. This chapter describes 13 components of the psychodynamic stance and situates them in historical and theoretical contexts. Several of these components are fairly unique and serve to distinguish psychodynamic therapy from other approaches. It is argued that the process of articulating one’s stance facilitates the selection and use of specific psychodynamic techniques. Further, when unexpected clinical events occur, a therapist’s stance can serve as a useful guide for difficult decisions. Throughout the chapter, the common mistakes of beginning therapists (e.g., intervening too quickly, placing their values on the patient) are explored and suggestions are provided.
The Process of Questioning
Authors: Sharpless Brian A.
Published: February 2019

Therapist questions are meant to generate patient information that is unknown to the therapist but needed for treatment. They are used to (a) facilitate free association/foster patient exploration and (b) to gain specific information about the patient, their problems, and the unique ways that they think, feel, behave, and respond to the therapy process. Suggestions are provided for the proper wording of questions as well as determining an appropriate frequency for their use. This is because an overuse of questions, or even the inclusion of irrelevant questions, can derail the therapy process and lead to alliance ruptures. However, questions can be used to meet a number of important clinical aims and are a necessary part of any treatment. The chapter ends with a consideration of how therapists can effectively handle patient questions.
Supportive Therapy Techniques Part I
Authors: Sharpless Brian A.
Published: February 2019

A number of patients seen in contemporary clinical practice are not appropriate for traditional insight-oriented therapy (i.e., expressive approaches). These may include sicker patients or those who are not interested in exploratory work. Supportive therapy refers to a flexible treatment approach that is intended to be responsive to the particular needs of these patients. Supportive therapy also benefits from the integration of techniques from other orientations (e.g., cognitive-behavioral therapy). After discussing supportive therapy more generally and differentiating it from the expressive approaches, this chapter focuses on two sets of supportive techniques. The first focuses on ways to support and enhance realistic patient self-esteem. The second set consists of techniques used to increase patient knowledge and build adaptive skills (e.g., psychoeducation, reality testing).
Repairing Ruptures in the Therapeutic Alliance
Authors: Sharpless Brian A.
Published: February 2019

:Ruptures (i.e., deteriorations or strains in the therapeutic alliance) are an inevitable part of any psychotherapy. They are not only common but are also clinically meaningful. If not adequately attended to, ruptures are associated with poor therapy outcome and premature termination. Fortunately, a strong research base is available that provides clinically useful guidance for identifying and resolving alliance ruptures. After a brief review of the theoretical and empirical literatures, a list of “markers” used to identify the two subtypes of ruptures (i.e., withdrawal and confrontation) is provided. Proper assessment of the subtype is critical, as they each require slightly different rupture resolution techniques across a four-stage process. Finally, a list of specific rupture resolution techniques is provided.
The Health Status of Veteran Employees Compared to Civilian Employees in Veterans Health Administration
Authors: Schult Tamara M , Schmunk Sandra K , Marzolf James R , Mohr David C
Published: February 2019

Introduction

Veterans Health Administration (VHA) is undergoing changes in the practice of health care focusing on approaches that prioritize veteran well-being. Given transformation efforts, opportunities exist to enhance the health and well-being of patients and employees alike – a significant proportion of whom are veterans. To date, differences in health status between veteran and civilian employees within VHA have not been examined.

Materials and Methods

Data from an annual organizational census survey with health promotion module conducted in 2015 were analyzed to estimate the prevalence of health risk behaviors, mental health, and chronic health conditions by veteran status within genders (n = 86,257). To further examine associations by gender between veteran status and health measures controlling for covariates, multivariate logistic regression analyses were utilized.

Results

Prevalence estimates generally indicated veterans have worse health status and health risk behaviors than their civilian counterparts. Results from multivariate logistic regression analyses indicated many significant associations between veteran status and health by gender controlling for other important demographic variables and a total comorbidity score. Compared to civilian employees within respective genders, both male and female veteran employees have increased odds of being a current smoker. Both male and female veteran employees have decreased odds of physical inactivity compared to civilian employees. For mental health and chronic health conditions, there are several conditions that veteran employees have increased odds for when compared to civilian employees of like gender; these include low back problems, arthritis, anxiety, depression, and sleep disorders.

Conclusions

Veteran employees in VHA have worse health status than their civilian counterparts on a number of measures of health risk behaviors, mental health, and chronic health conditions. Given current organizational priorities aimed at cultural transformation, the present time is an optimal one to work collaboratively to enhance the health and well-being services that are available for patients and employees alike. All employees, particularly our unique population of veteran employees, will benefit from such an approach.
Effect of 7 Months of Physical Training and Military Routine on the Bone Mass of Young Adults
Authors: de Avila Josiel Almeida , Melloni Mauro Augusto Schreiter , Pascoa Mauro Alexandre , Cirolini Vagner Xavier , Barbeta Camila Justino de Oliveira , de Avila Rafael Almeida , Gonçalves Ezequiel Moreira , Guerra-Junior Gil
Published: February 2019

Introduction

Physical activity (PA) has a great influence on bone mineral density (BMD) and bone mineral content (BMC), however longitudinal studies that seek to relate bone mass to physical activity are scarce and have a small sample size. The aim of this study was to evaluate and compare the effect of 7 months of military physical training (MPT), impact sports (IS), and swimming in the bone mass of young military adults.

Materials and Methods

A prospective study was conducted with 213 military school students (male and aged 19.2 ± 1.2 years) divided into three groups: MPT (n = 144), IS (n = 56), and Swimming (n = 13). Dual-energy X-ray absorptiometry was used to determine body composition (percentage of fat, fat mass, and fat-free mass) and bone mass (BMD, BMD Z-Score, total BMC, arm BMC, leg BMC, and trunk BMC), at the beginning of the military service and after 7 months of training.

Results

It was observed a significant increase in BMD, BMD Z-Score, total BMC and BMC of all segments analyzed for all groups (p < 0.01). There was a significantly greater variation in BMD of the IS group in relation to the MPT group (p < 0.01), and in the arm BMC of the MPT group in relation to the IS group (p < 0.05).

Conclusion

After 7 months of training, there were significant increases in BMC and BMD of all the groups evaluated. The bone response was associated with the muscular group used in the physical exercise and the IS group showed greater gain in BMD.
Impact of TBI, PTSD, and Hearing Loss on Tinnitus Progression in a US Marine Cohort
Authors: Clifford Royce E , Baker Dewleen , Risbrough Victoria B , Huang Mingxiong , Yurgil Kate A
Published: February 2019

Introduction

Mild TBI (TBI) is associated with up to a 75.7% incidence of tinnitus, and 33.0% of tinnitus patients at the US Veterans Administration carry a diagnosis of post-traumatic stress syndrome (PTSD). Yet factors contributing to new onset or exacerbation of tinnitus remain unclear.

Materials and Methods

Here we measure intermittent and constant tinnitus at two time points to ascertain whether pre-existing or co-occurring traumatic brain injury (TBI), hearing loss, or post-traumatic stress disorder (PTSD) predicts new onset, lack of recovery and/or worsening of tinnitus in 2,600 United States Marines who were assessed before and after a combat deployment.

Results

Ordinal regression revealed that constant tinnitus before deployment was likely to continue after deployment (odds ratio [OR] = 28.62, 95% confidence interval [CI]: 9.84,83.26). Prior intermittent tinnitus increased risk of post-deployment constant tinnitus (OR = 4.95, CI: 2.97,8.27). Likelihood of tinnitus progression increased with partial PTSD (OR = 2.39, CI: 1.50,3.80) and TBI (OR = 1.59, CI: 1.13,2.23), particularly for blast TBI (OR = 2.01, CI: 1.27,3.12) and moderate to severe TBI (OR = 2.57, CI: 1.46,4.51). Tinnitus progression also increased with low frequency hearing loss (OR = 1.94, CI: 1.05,3.59), high frequency loss (OR = 3.01, CI: 1.91,4.76) and loss across both low and high frequency ranges (OR = 5.73, CI: 2.67,12.30).

Conclusions

Screening for pre-existing or individual symptoms of PTSD, TBI, and hearing loss may allow for more focused treatment programs of comorbid disorders. Identification of those personnel vulnerable to tinnitus or its progression may direct increased acoustic protection for those at risk.
Effect of Chronic Low Back Pain and Post-Traumatic Stress Disorder on the Risk for Separation from the US Army
Authors: Benedict Timothy M , Singleton Michael D , Nitz Arthur J , Shing Tracie L , Kardouni Joseph R
Published: February 2019

Introduction

Co-morbid post-traumatic stress disorder (PTSD) and low back pain (LBP) are common reasons for increased disability in the Veteran communities. Medical discharge from the military represents a considerable financial cost to society. Little is currently known about the impact of LBP and PTSD as longitudinal risk factors for medical discharge from Active Duty military service.

Materials and Methods

A retrospective analysis of US Army Active Duty Soldiers from 2002 to 2012 was performed to determine the risk for medical discharge. Four levels of exposure for were identified as independent variables: no chronic LBP or PTSD, chronic LBP only, PTSD only, and co-morbid PTSD present with chronic LBP. Statistical analysis utilized modified Poisson regression controlling for sex, age, rank, time in service, deployment, mental health, sleep disorders, alcohol use, tobacco use, obesity, and military occupation. This study was approved by a Department of Defense Institutional Review Board.

Results

After controlling for potential confounding variables, the RR for chronic LBP and PTSD independently was 3.65 (95% CI: 3.59–3.72) and 3.64 (95% CI: 3.53–3.75), respectively, and 5.17 (95% CI: 5.01–5.33) when both were present.

Conclusions

This is the first study to identify a history of both chronic LBP and PTSD as substantial risk factors for medical discharge from the US Army. PTSD and chronic LBP may mutually reinforce one another and deplete active coping strategies, making Soldiers less likely to be able to continue military service. Future research should target therapies for co-morbid PTSD and chronic LBP as these conditions contribute a substantial increase in risk of medical discharge from the US Army.
Candida isolates causing candidemia show different degrees of virulence in Galleria mellonella
Authors: Marcos-Zambrano Laura Judith , Bordallo-Cardona María Ángeles , Borghi Elisa , Falleni Monica , Tosi Delfina , Muñoz Patricia , Escribano Pilar , Guinea Jesús
Published: February 2019

We aim to assess intra- and interspecies differences in the virulence of Candida spp. strains causing candidemia using the invertebrate Galleria mellonella model. We studied 739 Candida spp. isolates (C. albicans [n = 373], C. parapsilosis [n = 203], C. glabrata [n = 92], C. tropicalis [n = 53], and C. krusei [n = 18]) collected from patients with candidemia admitted to Gregorio Marañon Hospital (Madrid, Spain). Species-specific infecting inocula (yeast cells/larva) were adjusted (5 × 105 [C. albicans, and C. tropicalis], 2 × 106–5 × 106 [C. parapsilosis, C. glabrata, and C. krusei]) and used to infect 10 larvae per isolate; percentage of survival and median survival per isolate were calculated. According to the interquartile range of the median survival, isolates with a median survival under P25 were classified as of high-virulence and isolates with a median survival over P75 as of low virulence. The median survival of larvae infected with different species was variable: C. albicans (n = 2 days, IQR <1−3 days), C. tropicalis (n = 2 days, IQR 1.5−4 days), C. parapsilosis (n = 2 days, IQR 2−3.5 days), C. glabrata (n = 3 days, IQR 2−3 days), and C. krusei (n = 7 days, 6.5−>8 days) (P < .001). Differences in virulence among species were validated by histological examination (day +1 post-infection) in the larvae infected by the isolates of each virulence category and species. Virulence-related gene expression in C. albicans isolates did not reach statistical significance. We report species-specific virulence patterns of Candida spp. and show that isolates within a given species have different degrees of virulence in the animal model.
Electron-impact fine-structure excitation of Fe ii at low temperature
Authors: Wan Yier , Favreau C , Loch S D , McLaughlin B M , Qi Yueying , Stancil P C
Published: February 2019

Fe ii emission lines are observed from nearly all classes of astronomical objects over a wide spectral range from the infrared to the ultraviolet. To meaningfully interpret these lines, reliable atomic data are necessary. In the work presented here we focused on low-lying fine-structure transitions, within the ground term, due to electron impact. We provide effective collision strengths together with estimated uncertainties as functions of temperature of astrophysical importance (10−100 000 K). Due to the importance of fine-structure transitions within the ground term, the focus of this work is on obtaining accurate rate coefficients at the lower end of this temperature range, for applications in low-temperature environments such as the interstellar medium. We performed three different flavours of scattering calculations: (i) an intermediate coupling frame transformation (icft) R-matrix method, (ii) a Breit–Pauli R-matrix (bprm) method, and (iii) a Dirac Atomic R-matrix Code (darc). The icft and bprm calculations involved three different autostructure target models each. The darc calculation was based on a reliable 20 configuration, 6069 level atomic structure model. Good agreement was found with our bprm and darc collision results compared to previous R-matrix calculations. We present a set of recommended effective collision strengths for the low-lying forbidden transitions together with associated uncertainty estimates.
Multiwavelength survey of X-ray sources in the Sculptor Dwarf Spheroidal Galaxy
Authors: Arnason R M , Barmby P , Bahramian A , Maccarone T J , Zepf S E
Published: February 2019

We present an unprecedented, deep study of the primordial low-mass X-ray binary population in an isolated, lower metallicity environment. We perform follow-up observations of previously identified X-ray binary candidates in the Sculptor Dwarf Galaxy by combining a second Chandra observation with Spitzer and Gemini photometry, as well as Gemini spectroscopy of selected targets. Of the original nine bright X-ray sources identified, we are able to classify all but one as quasars, active galactic nuclei, or background galaxies. We further discover four new X-ray sources in the second-epoch Chandra observation. Three of these new sources are background sources and one is a foreground flaring star. We have found that Sculptor is effectively devoid of X-ray sources above a few 1034 erg s−1. If Sculptor is able to retain primordial binaries at a similar rate to globular clusters, this implies that bright X-ray binaries observed in globular clusters in the present epoch are all formed dynamically.