bluuebunny/crossref_metadata_2025 huggingface dataset:
Life History Diversity of Snake River Steelhead Populations between and within Management Categories
Authors: Copeland Timothy , Ackerman Michael W. , Wright Kristin K. , Byrne Alan
Published: March 2017

Grouping populations for management may overlook the fine-scale diversity underpinning the stability and resilience of meta-populations and fisheries. A bimodal timing distribution of summer-run steelhead Oncorhynchus mykiss (anadromous Rainbow Trout) historically was observed at Bonneville Dam (BON), the first barrier to upstream migration in the Columbia River basin. Early mode fish (A-run) tended to be younger and smaller (<78 cm) than later fish (B-run). While A-run fish spawn throughout the Columbia River basin, B-run fish spawn primarily in the Snake River basin. Managers used indices of these modes to make fishery decisions, and later these criteria were adopted for conservation. It is still unclear how life history and body size differences among wild Snake River populations are related to the categories at BON. We examined population parameters characterizing the two categories (date of passage at BON, length) and parameters directly affecting population dynamics (age composition, sex ratio). The life history portfolio of Snake River steelhead is quite diverse. There was broad overlap among populations in several respects, forming a gradient in life history characteristics rather than a dichotomous break. All populations produced adults <78 cm and adults returning after August 25. Median lengths of putative B-run populations were close to the criterion that was supposed to be a defining characteristic. In contrast, few A-run populations produced many adults ≥78 cm. Mean percentage of two-ocean fish was 52.1% for A-run populations and 82.0% for B-run populations. Mean age at spawn was greater in populations producing older smolts. Sex ratio was female biased, and older populations had greater percentages of females. Although the run-type dichotomy was useful for management of fisheries in the past, it is not useful for conservation. A combination of genetic stock identification at main-stem dams and population-specific monitoring in natal streams provides a unified framework for the assessment of fisheries management and conservation objectives.

Received March 2, 2016; accepted November 9, 2016 Published online March 10, 2017
An Updated Description of the Benefits and Consequences of Red Snapper Shrimp Trawl Bycatch Management Actions in the Gulf of Mexico
Authors: Gallaway Benny J. , Gazey W. J. , Cole J. G.
Published: March 2017

Populations of Red Snapper Lutjanus campechanus in the Gulf of Mexico remain overfished, but overfishing has been ended. Historically, rebuilding plans were based almost entirely on the reduction of shrimp trawl bycatch mortality, which was believed to account for 80% of the total juvenile Red Snapper mortality. This estimate was based on the assumption that juvenile Red Snapper had low rates of natural mortality. Bycatch reduction devices were believed to be capable of reducing bycatch mortality by more than 50%, which would enable the stock to rebuild without any other management actions. Over the years, new information has shown that natural mortality rates of juvenile Red Snapper are four times higher than originally estimated, and bycatch mortality is presently estimated to comprise only about 4% of the total juvenile mortality. Hence, bycatch reduction, regardless of the means by which it is achieved, will not be very effective for rebuilding the Red Snapper stock. Limits on the harvest of adult Red Snapper beginning in 2007 have put this species on the road to recovery, but care must be taken to maintain a conservative harvest if full recovery goals are to be met on schedule.

Received June 15, 2016; accepted December 8, 2016 Published online March 10, 2017
Reliable and Clinically Significant Change in Outcomes for Forensic Mental Health Inpatients: Use of the HoNOS-Secure
Authors: Dickens Geoffrey L. , O'Shea Laura E.
Published: March 2017

Outcomes measures are commonly derived from post-discharge recidivism, readmission, and mortality rates but information about common outcomes across admission is scant. We determined whether reliable and clinically significant change in risk-related need, behavior, functioning, and symptoms occurred during admission by analysing routinely collected HoNOS-secure data ( N = 418). We calculated between-group differences in baseline scores and rates of change, the proportion of patients for whom change was reliable, and, of those, the proportion whose scores fell by a clinically significant margin. Reliable change was demonstrated for 4.8% and 5.7% of patients on the HoNOS-secure scale and security scale respectively, and that change was rarely clinically significant. In a context in which services rarely report on routinely collected data for a range of outcomes, we found that HoNOS-secure captured little of any clinical change that may have occurred. Further research should determine whether the HoNOS-secure is a suitable tool for routine outcomes reporting.
The Relationship between Feigned Psychiatric Symptoms and Feigned Lack of Legal Knowledge among a Multi-Site Sample of Forensic Inpatients
Authors: Gottfried Emily D. , Vitacco Michael J. , Steadham Jennifer A.
Published: March 2017

The accurate assessment of feigning is a cornerstone of forensic evaluations. This study examined two feigning strategies defendants may use for the purpose of being found not competent to stand to trial: feigning psychiatric symptoms and feigning lack of legal knowledge. Participants included 203 forensic inpatients undergoing competency to stand trial assessments at two state hospitals. Each participant was administered the Miller Forensic Assessment of Symptoms Test and the Inventory of Legal Knowledge. Results indicated that there was a significant relationship between these two types of feigning (manual cut scores: χ2 (1, 203) = 23.02, p < .001) and the presence of one feigning strategy increased his or her risk for engaging in the other feigning strategy (e.g., using the manual cut scores, participants shown to be feigning psychiatric symptoms were 2.23 times more likely to feign lack of legal knowledge than those not feigning psychiatric symptoms). This article provides evidence of an increased risk of defendants employing a second feigning strategy when it is determined they are already using one strategy. These results encourage forensic evaluators to be cognizant of the nature of feigning and various strategies employed by individuals undergoing evaluations of competency.
Myeloid-derived cullin 3 promotes STAT3 phosphorylation by inhibiting OGT expression and protects against intestinal inflammation
Authors: Li Xinghui , Zhang Zhibin , Li Lupeng , Gong Wei , Lazenby Audrey J. , Swanson Benjamin J. , Herring Laura E. , Asara John M. , Singer Jeffrey D. , Wen Haitao
Published: March 2017

Signal transducer and activator of transcription 3 (STAT3) is a key mediator of intestinal inflammation and tumorigenesis. However, the molecular mechanism that modulates STAT3 phosphorylation and activation is not fully understood. Here, we demonstrate that modification of STAT3 with O-linked β-N-acetylglucosamine (O-GlcNAc) on threonine 717 (T717) negatively regulates its phosphorylation and targets gene expression in macrophages. We further found that cullin 3 (CUL3), a cullin family E3 ubiquitin ligase, down-regulates the expression of the O-GlcNAc transferase (OGT) and inhibits STAT3 O-GlcNAcylation. The inhibitory effect of CUL3 on OGT expression is dependent on nuclear factor E2–related factor-2 (Nrf2), which binds to the Ogt promoter region and increases gene transcription. Myeloid deletion of Cul3 led to defective STAT3 phosphorylation in colon macrophages, which was accompanied by exacerbated colonic inflammation and inflammation-driven tumorigenesis. Thus, this study identifies a new form of posttranslational modification of STAT3, modulating its phosphorylation, and suggests the importance of immunometabolism on colonic inflammation and tumorigenesis.
Pms2 and uracil-DNA glycosylases act jointly in the mismatch repair pathway to generate Ig gene mutations at A-T base pairs
Authors: Girelli Zubani Giulia , Zivojnovic Marija , De Smet Annie , Albagli-Curiel Olivier , Huetz François , Weill Jean-Claude , Reynaud Claude-Agnès , Storck Sébastien
Published: March 2017

During somatic hypermutation (SHM) of immunoglobulin genes, uracils introduced by activation-induced cytidine deaminase are processed by uracil-DNA glycosylase (UNG) and mismatch repair (MMR) pathways to generate mutations at G-C and A-T base pairs, respectively. Paradoxically, the MMR-nicking complex Pms2/Mlh1 is apparently dispensable for A-T mutagenesis. Thus, how detection of U:G mismatches is translated into the single-strand nick required for error-prone synthesis is an open question. One model proposed that UNG could cooperate with MMR by excising a second uracil in the vicinity of the U:G mismatch, but it failed to explain the low impact of UNG inactivation on A-T mutagenesis. In this study, we show that uracils generated in the G1 phase in B cells can generate equal proportions of A-T and G-C mutations, which suggests that UNG and MMR can operate within the same time frame during SHM. Furthermore, we show that Ung−/−Pms2−/− mice display a 50% reduction in mutations at A-T base pairs and that most remaining mutations at A-T bases depend on two additional uracil glycosylases, thymine-DNA glycosylase and SMUG1. These results demonstrate that Pms2/Mlh1 and multiple uracil glycosylases act jointly, each one with a distinct strand bias, to enlarge the immunoglobulin gene mutation spectrum from G-C to A-T bases.
The genome sequence of the wisent (Bison bonasus)
Authors: Wang Kun , Wang Lizhong , Lenstra Johannes A. , Jian Jianbo , Yang Yongzhi , Hu Quanjun , Lai Deyong , Qiu Qiang , Ma Tao , Du Zheng , Abbott Richard , Liu Jianquan
Published: March 2017

The wisent, also known as the European bison, was rescued from extinction approximately 80 years ago through the conservation of 12 individuals. Here, we present the draft genome sequence of a male wisent individual descended from this founding stock. A total of 366 billion base pairs (Gb) of raw reads from whole-genome sequencing of this wisent were generated using the Illumina HiSeq2000 platform. The final genome assembly (2.58 Gb) is composed of 29,074 scaffolds with an N50 of 4.7 Mb. 47.3% of the genome is composed of repetitive elements. We identified 21,542 genes and 58,385 non-coding RNAs. A phylogenetic tree based on nuclear genomes indicated sister relationships between bison and wisent and between the wisent-bison clade and yak. For 75 genes we obtained evidence of positive evolution in the wisent lineage. We provide the first genome sequence and gene annotation for the wisent. The availability of these resources will be of value for the future conservation of this endangered large mammal and for reconstructing the evolutionary history of the Bovini tribe.
Establishment of a human hepatocellular cell line capable of maintaining long-term replication of hepatitis B virus
Authors: Yao Wan-Ling , Ikeda Sotaro , Tsukamoto Yuta , Shindo Keiko , Otakaki Yukie , Qin Mian , Iwasawa Yoshikazu , Takeuchi Fumihiko , Kaname Yuki , Chou Yu-Chi , Chang Chungming , Watashi Koichi , Wakita Takaji , Noda Takeshi , Kato Hiroki , Fujita Takashi
Published: March 2017

Hepatitis B virus (HBV) is a virus whose replication cycle cannot be completely reproduced using cultured cell lines. Here, we report an engineered cell line capable of supporting the complete HBV life cycle. We generated HepG2 cells over-expressing the HBV entry receptor human NTCP (sodium taurocholate cotransporting polypeptide), and defective in RIG-I (retinoic acid-inducible gene-I)-like receptor signaling, by knocking down the IPS-1 (IFNβ-promoter stimulator-1) adaptor molecule. The resultant NtG20.i7 cells were susceptible to HBV, and its replication was detectable at 14 days post-infection and persisted for at least 35 days with a gradual increase of HBV core expression. The cells produced infectious HBV in the culture supernatant, and the addition of preS1 peptide myr47-WT, which blocks HBV entry, impaired the persistence of the infection. These findings suggest that the persistence of the infection was maintained by continuous release of infectious HBV virions and their re-infection. This system is useful for expanding our basic understanding of the HBV replication cycle and for screening of anti-HBV chemicals.
Patient portals and broadband internet inequality
Authors: Perzynski Adam T , Roach Mary Joan , Shick Sarah , Callahan Bill , Gunzler Douglas , Cebul Randall , Kaelber David C , Huml Anne , Thornton John Daryl , Einstadter Douglas
Published: March 2017

Background: Patient portals have shown potential for increasing health care quality and efficiency. Internet access and other factors influencing patient portal use could worsen health disparities.

Methods: Observational study of adults with 1 or more visits to the outpatient clinics of an urban public health care system from 2012 to 2015. We used mixed effects logistic regression to evaluate the association between broadband internet access and (1) patient portal initiation (whether a patient logged in at least 1 time) and (2) messaging, controlling for demographic and neighborhood characteristics.

Results: There were 243 248 adults with 1 or more visits during 2012–2015 and 70 835 (29.1%) initiated portal use. Portal initiation was 34.1% for whites, 23.4% for blacks, and 23.8% for Hispanics, and was lower for Medicaid (26.5%), Medicare (23.4%), and uninsured patients (17.4%) than commercially insured patients (39.3%). In multivariate analysis, both initiation of portal use (odds ratio [OR] = 1.24 per quintile, 95% confidence interval [CI], 1.23–1.24, P < .0001) and sending messages to providers (OR = 1.15, 95%CI, 1.09–1.14, P < .0001) were associated with neighborhood broadband internet access.

Conclusions: The majority of adults with outpatient visits to a large urban health care system did not use the patient portal, and initiation of use was lower for racial and ethnic minorities, persons of lower socioeconomic status, and those without neighborhood broadband internet access. These results suggest the emergence of a digital divide in patient portal use. Given the scale of investment in patient portals and other internet-dependent health information technologies, efforts are urgently needed to address this growing inequality.
Systematic Review: A Prevention-Based Model of Neuropsychological Assessment for Children With Medical Illness
Authors: Hardy Kristina K. , Olson Katie , Cox Stephany M. , Kennedy Tess , Walsh Karin S.
Published: March 2017

Objective

Many pediatric chronic illnesses have shown increased survival rates, leading to greater focus on cognitive and psychosocial issues. Neuropsychological services have traditionally been provided only after significant changes in the child’s cognitive or adaptive functioning have occurred. This model of care is at odds with preventative health practice, including early identification and intervention of neuropsychological changes related to medical illness. We propose a tiered model of neuropsychological evaluation aiming to provide a preventative, risk-adapted level of assessment service to individuals with medical conditions impacting the central nervous system based on public health and clinical decision-making care models.

Methods

Elements of the proposed model have been used successfully in various pediatric medical populations. We summarize these studies in association with the proposed evaluative tiers in our model.

Results and Conclusions

This model serves to inform interventions through the various levels of assessment, driven by evidence of need at the individual level in real time.
Medina® Embolization Device for the Treatment of Intracranial Aneurysms: Safety and Angiographic Effectiveness at 6 Months
Authors: Sourour Nader-Antoine , Vande Perre Saskia , Maria Federico Di , Papagiannaki Chrysanthi , Gabrieli Joseph , Pistocchi Silvia , Bartolini Bruno , Degos Vincent , Carpentier Alexandre , Chiras Jacques , Clarençon Frédéric
Published: March 2017

BACKGROUND

The Medina Embolization Device (MED) is a new concept device that combines the design of a detachable coil and the one of an intrasaccular flow disruption device.

OBJECTIVE

To evaluate the feasibility, safety, and 6- to 9-mo effectiveness of this new device for the treatment of intracranial wide-necked aneurysms.

METHODS

Twelve patients (10 females, mean age = 56 yr) with 13 wide-necked intracranial aneurysms (3 ruptured; 10 unruptured) were treated by means of the MED from January 2015 to October 2015. In 15% of the cases, MEDs were used in a standalone fashion; in 85% of the cases, additional regular coils were used. Adjunctive compliant balloon was used in 4 of 13 cases (31%). Procedure-related complications were systematically recorded; discharge and 6- to 9-mo follow-up modified Rankin Scale was assessed. Angiographic follow-up was performed with a mean delay of 5.5 ± 1.7 mo. Occlusion rate was evaluated in postprocedure and at midterm follow-up using the Roy–Raymond scale.

RESULTS

The deployment of the MED was feasible in all cases. No perforation was recorded. One case of thromboembolic complication was observed in a ruptured anterior communicating artery aneurysm, without any clinical consequence at follow-up. Grade A occlusion rate was 61.5% in postprocedure and 83% at 6-mo follow-up. Two cases (17%) of recanalization were documented angiographically.

CONCLUSION

The MED is a new generation device combining the design of a detachable coil and an intrasaccular flow disruption device. According to our early experience, this device is safe and provides a satisfactory occlusion rate at angiographic follow-up of 6 mo.
Microbiological Etiology and Treatment of Complicated Skin and Skin Structure Infections in Diabetic and Nondiabetic Patients in a Population-Based Study
Authors: Jääskeläinen Iiro H. , Hagberg Lars , Forsblom Erik , Järvinen Asko
Published: March 2017

Background

Diabetes is a major risk factor for skin and skin structure infection (SSSI), and the global burden of diabetics with SSSI is enormous. The more complex microbiology of diabetic foot infection (DFI) is well established, but it is not known whether microbiological etiology differs between diabetics and nondiabetics in other disease entities under the umbrella of complicated SSSI (cSSSI).

Methods

This retrospective, population-based study included patients with cSSSI, and it was conducted in 2 Nordic cities with a low prevalence of antimicrobial resistance. In analyses, patients (N = 460) were separated into 3 groups: diabetics (n = 119), nondiabetics (n = 271), and patients with DFI (n = 70).

Results

After exclusion of patients with DFI, there was no difference in the microbiological etiology or initial antimicrobial treatment of cSSSI between diabetics and nondiabetics. Gram-positive bacteria encountered 70% of isolations in diabetics and 69% in nondiabetics, and the empirical treatment covered initial pathogens in 81% and 86% of patients, respectively. However, diabetes was the only background characteristic in the propensity score-adjusted analysis associated with broad-spectrum antimicrobial use and longer antibiotic treatment duration. Patients with DFI had Gram-negative and polymicrobial infection more often than nondiabetics.

Conclusions

These observations suggest that diabetics without DFI are not different in the causative agents of cSSSI, although they are more exposed to antimicrobial therapy of inappropriate extended spectrum and long duration. Broad-spectrum coverage was clearly needed only in DFI. A clear opportunity for antimicrobial stewardship was detected in the rapidly growing population of diabetic patients with cSSSI.
ALMA deep field in SSA22: Blindly detected CO emitters and [C ii] emitter candidates
Authors: Hayatsu Natsuki H. , Matsuda Yuichi , Umehata Hideki , Yoshida Naoki , Smail Ian , Swinbank A. Mark , Ivison Rob , Kohno Kotaro , Tamura Yoichi , Kubo Mariko , Iono Daisuke , Hatsukade Bunyo , Nakanishi Kouichiro , Kawabe Ryohei , Nagao Tohru , Inoue Akio K. , Takeuchi Tsutomu T. , Lee Minju , Ao Yiping , Fujimoto Seiji , Izumi Takuma , Yamaguchi Yuki , Ikarashi Soh , Yamada Toru
Published: March 2017

We report the identification of four millimeter line-emitting galaxies with the Atacama Large Milli/submillimeter Array (ALMA) in SSA22 Field (ADF22). We analyze the ALMA 1.1-mm survey data, with an effective survey area of 5 arcmin2, frequency ranges of 253.1–256.8 and 269.1–272.8 GHz, angular resolution of 0${^{\prime\prime}_{.}}$7 and rms noise of 0.8 mJy beam−1 at 36 km s−1 velocity resolution. We detect four line-emitter candidates with significance levels above 6σ. We identify one of the four sources as a CO(9–8) emitter at z = 3.1 in a member of the proto-cluster known in this field. Another line emitter with an optical counterpart is likely a CO(4–3) emitter at z = 0.7. The other two sources without any millimeter continuum or optical/near-infrared counterpart are likely to be [C ii] emitter candidates at z = 6.0 and 6.5. The equivalent widths of the [C ii] candidates are consistent with those of confirmed high-redshift [C ii] emitters and candidates, and are a factor of 10 times larger than that of the CO(9–8) emitter detected in this search. The [C ii] luminosity of the candidates are 4–7 × 108 L⊙. The star formation rates (SFRs) of these sources are estimated to be 10–20 M⊙ yr−1 if we adopt an empirical [C ii] luminosity–SFR relation. One of them has a relatively low S/N ratio, but shows features characteristic of emission lines. Assuming that at least one of the two candidates is a [C ii] emitter, we derive a lower limit of [C ii]-based star formation rate density (SFRD) at z ∼ 6. The resulting value of >10−2 M⊙ yr−1 Mpc−3 is consistent with the dust-uncorrected UV-based SFRD. Future millimeter/submillimeter surveys can be used to detect a number of high-redshift line emitters, with which to study the star formation history in the early universe.
Postoperative confusion in older adults
Authors: Segal-Gidan Freddi
Published: March 2017

The development of postoperative confusion in older patients is increasingly being recognized as clinically significant because it is becoming more common as the population ages. Postoperative delirium and postoperative cognitive dysfunction differ in time course of development. Risk factors other than age include certain medications as well as anesthesia (both the type and amount used). Postoperative delirium and postoperative cognitive dysfunction appear to increase a patient's risk for developing dementia. Routine preoperative screening may help to identify patients with preexisting cognitive impairment who are at greatest risk for developing postoperative delirium or postoperative cognitive dysfunction.
The Digital Drag and Drop Pillbox
Authors: Granger Bradi B. , Locke Susan C. , Bowers Margaret , Sawyer Tenita , Shang Howard , Abernethy Amy P. , Bloomfield Richard A. , Gilliss Catherine L.
Published: March 2017

Objective:

We present the design and feasibility testing for the “Digital Drag and Drop Pillbox” (D-3 Pillbox), a skill-based educational approach that engages patients and providers, measures performance, and generates reports of medication management skills.

Methods:

A single-cohort convenience sample of patients hospitalized with heart failure was taught pill management skills using a tablet-based D-3 Pillbox. Medication reconciliation was conducted, and aptitude, performance (% completed), accuracy (% correct), and feasibility were measured.

Results:

The mean age of the sample (n = 25) was 59 (36–89) years, 50% were women, 62% were black, 46% were uninsured, 46% had seventh-grade education or lower, and 31% scored very low for health literacy. However, most reported that the D-3 Pillbox was easy to read (78%), easy to repeat-demonstrate (78%), and comfortable to use (tablet weight) (75%). Accurate medication recognition was achieved by discharge in 98%, but only 25% reported having a “good understanding of my responsibilities.”

Conclusions:

The D-3 Pillbox is a feasible approach for teaching medication management skills and can be used across clinical settings to reinforce skills and medication list accuracy.
Update on adrenal insufficiency: diagnosis and management in pregnancy
Authors: Langlois Fabienne , Lim Dawn S.T. , Fleseriu Maria
Published: March 2017

Purpose of review

Adrenal insufficiency in pregnancy, although relatively rare, has significant clinical implications on both maternal and fetal outcomes. Hypothalamo–pituitary–adrenal axis dynamics and physiological changes are complex, thus diagnosis and management of adrenal insufficiency in pregnancy remain challenging.

Recent findings

Studies consistently demonstrate a rise in total serum cortisol with pregnancy, but less data are available on free cortisol levels. Salivary cortisol values have been measured in normal pregnancy and in a few studies using healthy nonpregnant women controls. Although this adds to our current knowledge of hypothalamo–pituitary–adrenal axis changes in pregnancy, clear-cut cortisol reference ranges are yet to be established. Serum cortisol and the cosyntropin stimulation test (albeit with higher peak cortisol thresholds) are currently the diagnostic tests of choice. Hydrocortisone is the preferred glucocorticoid replacement in pregnancy as it is inactivated by placental 11-β-hydroxysteroid dehydrogenase 2; dose titration may be required, but should be individualized depending on clinical course and mode of delivery.

Further studies on the long-term effects of maternal glucocorticoid regimens on the fetus and potential modulators of fetal glucocorticoid sensitivity and placental 11-β-hydroxysteroid dehydrogenase 2 are needed and will be useful in guiding clinical management strategies in pregnant women with adrenal insufficiency.
Health-Related Quality of Life After the Diagnosis of Locally Advanced or Advanced Prostate Cancer
Authors: Zajdlewicz Leah , Hyde Melissa K. , Lepore Stephen J. , Gardiner Robert A. , Chambers Suzanne K.
Published: March 2017

Background:

Approximately 20% of men with a diagnosis of prostate cancer present with locally advanced or advanced disease. Few studies consider longer-term impact of disease progression and treatment adverse effects on health-related quality of life (QoL) of these men.

Objective:

Describe changes in health-related QoL over 5 years for men with newly diagnosed locally advanced or advanced prostate cancer.

Interventions/Methods:

Eighty-one men with locally advanced or advanced prostate cancer referred to the study by their treating urologist completed a self-administered questionnaire assessing distress, cancer-specific distress, decision regret, satisfaction with life, and global and disease-specific health-related QoL. Questionnaires were administered close to diagnosis (baseline), 2, 6, 12, 24, 36, 48, and 60 months’ follow-up.

Results:

Men were of mean age 68.3 (SD, 7.9) years and at mean of 31.9 (SD, 50.5) days postdiagnosis. The most common treatment received was androgen deprivation therapy (95.1%) or radiation therapy (79%). The proportion of men classified as distressed (Distress Thermometer) ranged from 46.3% (baseline) to 32.6% (60 months). Decrements in physical QoL were found at 2, 6, 12, 24, 36, and 48 months compared with baseline. Life satisfaction ratings were lower at 6 months compared with baseline. Sexual concerns were consistently high across the 5 years (Expanded Prostate Cancer Index Composite <30).

Conclusions:

In the context of advanced disease, results indicate that health-related QoL fluctuates from diagnosis to 5 years later. A substantial proportion remained distressed at 5-year follow-up.

Implications for Practice:

Care frameworks supporting ongoing assessment of health-related QoL concerns of men with advanced prostate cancer are needed with a particular focus on sexual adjustment.
The Impact of Neonatal Simulations on Trainees’ Stress and Performance: A Parallel-Group Randomized Trial*
Authors: Lizotte Marie-Hélène , Janvier Annie , Latraverse Véronique , Lachance Christian , Walker Claire-Dominique , Barrington Keith J. , Moussa Ahmed
Published: March 2017

Objectives:

Assess impact of neonatal simulation and simulated death on trainees’ stress and performance.

Design:

A parallel-group randomized trial (November 2011 to April 2012).

Setting:

Sainte-Justine University Hospital, Montreal, Canada.

Subjects:

Sixty-two pediatric trainees eligible, 59 consented, and 42 completed the study.

Interventions:

Trainees performed two simulations where a term neonate was born pulseless. They were randomized to start with either survival (manikin responded to appropriate resuscitation) or death scenario (manikin remained pulseless despite resuscitation).

Measurements and Main Results:

Performance was assessed using the Neonatal Resuscitation Program megacode score sheet by two reviewers. Subjective stress was assessed with a questionnaire. Three salivary cortisol (objective stress) values were compared: at baseline (T0: during lecture), presimulation (T1), and postsimulation (T2: after first scenario). Performance scores were similar in both groups in the first (83% vs 82%; p = 0.85) and second scenarios (82% vs 79 %; p = 0.87). Salivary cortisol levels at T0 (0.10 vs 0.10; p = 0.54), T1 (0.15 vs 0.11; p = 0.35), and T2 (0.23 vs 0.17; p = 0.23) did not differ between groups. Perceived stress level was six out of 10 in survival group versus seven out of 10 in death group (p = 0.19). Salivary cortisol increased significantly from T0 to T1 (p < 0.01). T2 cortisol levels were significantly higher than T1 (p< 0.001), yet this increase was not scenario dependent (p = 0.41) nor associated with performance on either scenario. Subscores for bag mask ventilation were lower than subscores for advanced resuscitation skills.

Conclusions:

Neonatal simulations cause significant anticipatory and participatory stress. Despite this, trainees’ performance score in simulation was over 80%. Simulated death did not impact performance, magnitude of rise in salivary cortisol level, and perceived stress level. Trainees performed better at advanced resuscitation skills (which are rarely needed) compared with basic skills routinely performed in practice.
The Relationship Between Mental Health, Disease Severity, and Genetic Risk for Depression in Early Rheumatoid Arthritis
Authors: Euesden Jack , Matcham Faith , Hotopf Matthew , Steer Sophia , Cope Andrew P. , Lewis Cathryn M. , Scott Ian C.
Published: March 2017

Objective

Reduced mental health (MH) is prevalent in rheumatoid arthritis (RA). Although longitudinal studies are limited, there is evidence that depression is associated with worse disease outcomes. We evaluated reciprocal relationships between MH, RA severity, and genetic risks for depression for 2 years in a well-characterized cohort of RA patients.

Methods

We evaluated 520 early RA patients previously enrolled to two clinical trials. MH was measured using the short form-36 MH domain and mental component summary scores (MCS). MCS/MH associations over 2 years with disease activity (disease activity score on a 28-joint count), disability (health assessment questionnaire), pain visual analog scale scores, and a weighted genetic risk score for depression were tested using linear mixed-effects and regression models.

Results

Poorer MH was associated with worse RA outcomes. Lower MCS scores (indicating worse MH) were seen in patients with a greater genetic risk for depression (weighted genetic risk score: coefficient = −1.21, p = .013). Lower baseline MCS was associated with lower 2-year improvements in disease activity score on a 28-joint count (coefficient = −0.02, p < .001), pain (coefficient = −0.33, p < .001), and health assessment questionnaire (coefficient = −0.01, p = .006). Baseline MCS was associated with changes in the swollen joint count (coefficient = −0.09, p < .001) and patient global assessment (coefficient = −0.28, p < .001) but not the tender joint count (p = .983) and erythrocyte sedimentation rate (p = .973). Only baseline pain visual analog scale (coefficient = −0.07, p = .002) was associated with 2-year changes in MCS.

Conclusions

Reduced baseline MH was associated with lower improvements in disease activity, disability, and pain for 2 years, supporting current national guidelines recommending screening for depression in RA. Pain had a bidirectional relationship with MH. Depression genetic risk had a significant association with MH.
Environmental correlates of internal coloration in frogs vary throughout space and lineages
Authors: Franco-Belussi Lilian , Provete Diogo Borges , de Oliveira Classius
Published: March 2017

Internal organs of ectotherms have melanin-containing cells. Several studies analyzed their developmental origin, role in immunity, and hormonal regulation. However, little is known about how environmental variables influence the distribution and quantity of organ coloration. Here, we addressed how environmental variables (temperature, UV, and photoperiod) influence the internal coloration of amphibians after controlling for spatial and phylogenetic autocorrelations. Coloration in all organs was correlated with phylogeny. However, the coloration of the heart, kidneys, and rectum of hylids,R. schneideri,someLeptodactylus,andProceratophryswere influenced by temperature and photoperiod, whereas that of the testicle, lumbar parietal peritoneum, lungs, and mesenterium of Leiuperinae, Hylodidae,Adenomera,mostLeptodactyluswere influenced by UVB and temperature variation. Therefore, the amount of internal melanin seems to be a key trait influencing species distribution of frogs throughout space, since it can protect internal organs against the deleterious effect of high UV-B, temperature variation, and photoperiod.

Significance

The functions of internal coloration in fishes and frogs are little known. Internal pigmentation is commonly altered in fish and the degree of response is correlated with body transparency levels, suggesting possible adaptive functions. Here, we assume that internal melanin has protective functions against UV-B, temperature variation, and photoperiod. Thus it could influence frogs species distribution throughout space. The melanin coloration of each organ was influenced by distinct environmental variables depending on the lineages of species. Our results could direct further studies about the functions of internal coloration.
First landscape of binding to chromosomes for a domesticated mariner transposase in the human genome: diversity of genomic targets of SETMAR isoforms in two colorectal cell lines
Authors: Antoine-Lorquin Aymeric , Arnaoty Ahmed , Asgari Sassan , Batailler Martine , Beauclair Linda , Belleannée Catherine , Bire Solenne , Buisine Nicolas , Coustham Vincent , Girault Alban , Guyetant Serge , Lecomte Thierry , Piégu Benoît , Pitard Bruno , Stévant Isabelle , Bigot Yves
Published: March 2017

Setmaris a 3-exons gene coding a SET domain fused to aHsmar1transposase. Its different transcripts theoretically encode 8 isoforms with SET moieties differently spliced.In vitro,the largest isoform binds specifically toHsmar1DNA ends and with no specificity to DNA when it is associated with hPso4. In colon cell lines, we found they bind specifically to two chromosomal targets depending probably on the isoform,Hsmar1ends and sites with no conserved motifs. We also discovered that the isoforms profile was different between cell lines and patient tissues, suggesting the isoforms encoded by this gene in healthy cells and their functions are currently not investigated.
Clinically Useful Brain Imaging for Neuropsychiatry: How Can We Get There?
Authors: Milham Michael P. , Craddock R. Cameron , Klein Arno
Published: March 2017

Despite decades of research, visions of transforming neuropsychiatry through the development of brain imaging-based ‘growth charts’ or ‘lab tests’ have remained out of reach. In recent years, there is renewed enthusiasm about the prospect of achieving clinically useful tools capable of aiding the diagnosis and management of neuropsychiatric disorders. The present work explores the basis for this enthusiasm. We assert that there is no single advance that currently has the potential to drive the field of clinical brain imaging forward. Instead, there has been a constellation of advances that, if combined, could lead to the identification of objective brain imaging-based markers of illness. In particular, we focus on advances that are helping to: 1) elucidate the research agenda for biological psychiatry (e.g., neuroscience focus, precision medicine), 2) shift research models for clinical brain imaging (e.g., big data exploration, standardization), 3) break down research silos (e.g., open science, calls for reproducibility and transparency), and 4) improve imaging technologies and methods. While an arduous road remains ahead, these advances are repositioning the brain imaging community for long-term success.
Managed woodlot revealed a trade-off between edible leaves and timber production inVitex donianaSweet (Lamiaceae)
Authors: N’Danikou Sognigbé , Tchokponhoué Dèdéou A. , Houdégbé Aristide C. , Agossou Aboègnonhou O.C. , Achigan-Dako Enoch G. , Assogba Komlan Françoise , Vodouhè Raymond S. , Ahanchédé Adam
Published: March 2017

Vitex donianaSweet is a major wild-harvested tree resource for food in Benin. However, the species is under threats characterised by increasing human pressure on remnant populations. This study represents the first to explore species’ response to biotic stress. We tested the response ofV. donianato coppicing and fertilization. Two stump heights (20 and 40 cm) in combination with three organic manure rates (0.5; 1 and 1.5 kg per seedling), with eight replicates were tested in a randomised complete block design. We used mixed effect models with pseudoreplication, and the maximum likelihood method to compare effects of fixed factors on sprouting vigour, sprout growth and biomass yield in the short (12 months) and medium (5 years) terms. Results indicated that stump height significantly affected sprouting and all growth parameters, in the short and medium terms. However, there seemed a delayed effect of manure. We found initial seedling growth also an important factor. The hidden effect of stump height on biomass yield is discussed. Findings clearly indicate a trade-off between edible leaves and timber production by managed woodlot. Implications of findings for further investigation of above and below ground biomass dynamics and resources allocation in treated trees are discussed.

Highlights

A clear trade-off between edible leaves and timber production is observed in managedVitex donianaSweet woodlot. Coppicing as a biotic stress induced important physiological changes that merit further investigations.
Learning to See Again: Biological Constraints on Cortical Plasticity and the Implications for Sight Restoration Technologies
Authors: Beyeler Michael , Rokem Ariel , Boynton Geoffrey M. , Fine Ione
Published: March 2017

1. ABSTRACT

The “bionic eye” – so long a dream of the future – is finally becoming a reality with retinal prostheses available to patients in both the US and Europe. However, clinical experience with these implants has made it apparent that the vision provided by these devices differs substantially from normal sight. Consequently, the ability to learn to make use of this abnormal retinal input plays a critical role in whether or not some functional vision is successfully regained. The goal of the present review is to summarize the vast basic science literature on developmental and adult cortical plasticity with an emphasis on how this literature might relate to the field of prosthetic vision. We begin with describing the distortion and information loss likely to be experienced by visual prosthesis users. We then define cortical plasticity and perceptual learning, and describe what is known, and what is unknown, about visual plasticity across the hierarchy of brain regions involved in visual processing, and across different stages of life. We close by discussing what is known about brain plasticity in sight restoration patients and discuss biological mechanisms that might eventually be harnessed to improve visual learning in these patients.
DroNc-Seq: Deciphering cell types in human archived brain tissues by massively-parallel single nucleus RNA-seq
Authors: Habib Naomi , Basu Anindita , Avraham-Davidi Inbal , Burks Tyler , Choudhury Sourav R. , Aguet François , Gelfand Ellen , Ardlie Kristin , Weitz David A , Rozenblatt-Rosen Orit , Zhang Feng , Regev Aviv
Published: March 2017

Single nucleus RNA-Seq (sNuc-Seq) profiles RNA from tissues that are preserved or cannot be dissociated, but does not provide the throughput required to analyse many cells from complex tissues. Here, we develop DroNc-Seq, massively parallel sNuc-Seq with droplet technology. We profile 29,543 nuclei from mouse and human archived brain samples to demonstrate sensitive, efficient and unbiased classification of cell types, paving the way for charting systematic cell atlases.
Beyond Reward Prediction Errors: Human Striatum Updates Rule Values During Learning
Authors: Ballard Ian , Miller Eric M. , Piantadosi Steven T. , Goodman Noah , McClure Samuel M.
Published: March 2017

Humans naturally group the world into coherent categories defined by membership rules. Rules can be learned implicitly by building stimulus-response associations using reinforcement learning (RL) or by using explicit reasoning. We tested if the striatum, in which activation reliably scales with reward prediction error, would track prediction errors in a task that required explicit rule generation. Using functional magnetic resonance imaging during a categorization task, we show that striatal responses to feedback scale with a “surprise” signal derived from a Bayesian rule-learning model and are inconsistent with RL prediction error. We also find that striatum and caudal inferior frontal sulcus (cIFS) are involved in updating the likelihood of discriminative rules. We conclude that the striatum, in cooperation with the cIFS, is involved in updating the values assigned to categorization rules when people learn using explicit reasoning.
Combining Bayesian Approaches and Evolutionary Techniques for the Inference of Breast Cancer Networks
Authors: Beretta Stefano , Castelli Mauro , Gonçalves Ivo , Merelli Ivan , Ramazzotti Daniele
Published: March 2017

Gene and protein networks are very important to model complex large-scale systems in molecular biology. Inferring or reverseengineering such networks can be defined as the process of identifying gene/protein interactions from experimental data through computational analysis. However, this task is typically complicated by the enormously large scale of the unknowns in a rather small sample size. Furthermore, when the goal is to study causal relationships within the network, tools capable of overcoming the limitations of correlation networks are required. In this work, we make use of Bayesian Graphical Models to attach this problem and, specifically, we perform a comparative study of different state-of-the-art heuristics, analyzing their performance in inferring the structure of the Bayesian Network from breast cancer data.
A modified GC-specific MAKER gene annotation method reveals improved and novel gene predictions of high and low GC content inOryza sativa
Authors: Bowman Megan J. , Pulman Jane A. , Liu Tiffany L. , Childs Kevin L.
Published: March 2017

Accurate structural annotation depends on well-trained gene prediction programs. Training data for gene prediction programs are often chosen randomly from a subset of high-quality genes that ideally represent the variation found within a genome. One aspect of gene variation is GC content, which differs across species and is bimodal in grass genomes. We find that gene prediction programs trained on genes with random GC content do not completely predict all grass genes with extreme GC content. We present a new GC-specific MAKER annotation protocol to predict new and improved gene models and assess the biological significance of this method inOryza sativa.
Is the 25-year hepatitis C marathon coming to an end to declare victory?
Authors: Ahmed Khulood , Almashhrawi Ashraf , Ibdah Jamal A. , Tahan Veysel
Published: March 2017

Hepatitis C virus (HCV) which was originally recognized as posttransfusion non-A, non-B hepatitis has been a major global health problem affecting 3% of the world population. Interferon/peginterferon and ribavirin combination therapy was the backbone of chronic HCV therapy for two decades of the journey. However, the interferon based treatment success rate was around 50% with many side effects. Many chronic HCV patients with psychiatric diseases, or even cytopenias, were ineligible for HCV treatment. Now, we no longer need any injectable medicine. New direct-acting antiviral agents against HCV allowed the advance of interferon-free and ribavirin-free oral regimens with high rates of response and tolerability. The cost of the medications should not be a barrier to their access in certain parts of the world. While we are getting closer, we should still focus on preventing the spread of the disease, screening and delivering the cure globally to those in need. In the near future, development of an effective vaccine against HCV would make it possible to eradicate HCV infection worldwide completely.
Segregation lift: A general mechanism for the maintenance of polygenic variation under seasonally fluctuating selection
Authors: Wittmann Meike J. , Bergland Alan O. , Feldman Marcus W. , Schmidt Paul S. , Petrov Dmitri A.
Published: March 2017

Most natural populations are affected by seasonal changes in temperature, rainfall, or resource availability. Seasonally fluctuating selection could potentially make a large contribution to maintaining genetic polymorphism in populations. However, previous theory suggests that the conditions for multi-locus polymorphism are restrictive. Here we explore a more general class of models with multi-locus seasonally fluctuating selection in diploids. In these models, loci first contribute additively to a seasonal score, with a dominance parameter determining the relative contributions of heterozygous and homozygous loci. The seasonal score is then mapped to fitness via a monotonically increasing function, thereby accounting for epistasis. Using mathematical analysis and individual-based simulations, we show that stable polymorphism at many loci is possible if currently favored alleles are sufficiently dominant with respect to the additive seasonal score (but not necessarily with respect to fitness itself). This general mechanism, which we call “segregation lift”, operates for various genotype-to-fitness maps and includes the previously known mechanism of multiplicative selection with marginal overdominance as a special case. We show that segregation lift may arise naturally in situations with antagonistic pleiotropy and seasonal changes in the relative importance of traits for fitness. Segregation lift is not affected by problems of genetic load and is robust to differences in parameters across loci and seasons. Under segregation lift, loci can exhibit conspicuous seasonal allele-frequency fluctuations, but often fluctuations may also be small and hard to detect. Via segregation lift, seasonally fluctuating selection might contribute substantially to maintaining genetic variation in natural populations.