bluuebunny/crossref_metadata_2025 huggingface dataset:
Reproductive characteristics of three small-bodied cuttlefish in subtropical waters
Authors: Beasley Amanda L. , Hall Karina C. , Latella Coral I. , Harrison Peter L. , Morris Stephen G. , Scott Anna
Published: December 2017

Life history information for many commercially important cuttlefish is lacking, and thus the effects of long-term harvest remain unknown. The present study investigated the reproductive mode and seasonality of three small-bodied cuttlefish (Sepia opipara, S. plangon and S. rozella) in subtropical eastern Australia. Monthly samples were collected over 2 years and examined for gonadal development, size at sexual maturity, potential fecundity, size of mature oocytes and spermatophores, and temporal variation in maturity stages and gonadal weight relative to seawater temperature. All species showed reproductive characteristics consistent with a terminal multiple spawning mode, with S. opipara and S. rozella likely to be intermittent batch spawners, whereas S. plangon spawned continuously. Spawning occurred year round for all species, but S. opipara and S. rozella showed greater seasonality than S. plangon, peaking in autumn–spring. The biggest species, S. opipara, matured at a larger size than the others, had the greatest potential fecundity (the highest documented for any cuttlefish) and the largest spermatophore sizes. In contrast, S. rozella and S. plangon had much larger mature oocytes than S. opipara. These results further highlight the diversity of reproductive characteristics in cuttlefish, and the need for species-specific information for fishery and conservation management plans.
Effect of high magnetic field on the pearlite transformation of Al-containing steel
Authors: Xin Rui , Wu Kaiming , Zhang Guohong , Hou Tingping , Ma Guoyong , Qiao Wenwei , Zhao Huazhong
Published: December 2017

Comparative studies were carried out on the effect of high magnetic field on the pearlite transformation of Al-containing high carbon steels under the furnace slow cooling condition. For 1.37Al-bearing high carbon steel, the amount of pearlite was only 6 ± 3 vol.-% without magnetic field, whereas full pearlite was obtained under a 12-T high magnetic field. For free-Al high carbon steel, no pearlite transformation occurred, whereas lots of bainite were formed under a 12-T high magnetic field. In addition, the interlamellar spacing of pearlite increased from 100 ± 7 to 112 ± 18 nm by the application of a 12-T magnetic field. It has been proved that the pearlite transformation of high carbon steel was promoted by high magnetic field and by the addition of aluminium.

This is part of a thematic issue on Pearlitic Steel Wires.
Capital accumulation and capital controls in South Africa: a class perspective
Authors: Alami Ilias
Published: December 2017

The article analyses capital controls (CC) in South Africa in light of the historically and geographically specific social relations of production. It highlights the role that CC have historically played in reproducing particular forms of capital accumulation, and sheds light on the CC currently implemented by the state. The analysis draws upon quantitative data from the national accounts, descriptive data on CC from policy documents, and interviews conducted during a period of extensive fieldwork. The article makes three main arguments. First, CC have played a key role in facilitating the reproduction of essential capitalist social forms, namely the state and money, and have been instrumental in the management of class relations. Second, the concrete forms that CC have taken are inseparable from the historical-geographical specificity of accumulation and the uneven unfolding of crises and social class struggles. Third, working classes have had an active (though indirect) role in shaping CC policies.
Military corruption in war: stealing and connivance among Zimbabwean foot soldiers in the Democratic Republic of Congo (1998–2002)
Authors: Maringira Godfrey
Published: December 2017

This article examines the ways in which Zimbabwean foot soldiers engaged in military corrupt activities, stealing army rations from the trenches to resell in neighbouring civilian communities and Congolese soldiers in the Democratic Republic of Congo (DRC). The practice became widespread among and between senior and junior officers. However, this practice did not end with the war; rather it was carried over from the DRC war to the Zimbabwean army barracks. The article contends that the practice of stealing army rations was a deeply unprofessional practice. The article draws from life history stories of Zimbabwean former soldiers who deserted the army and are now living in South Africa.
Stochasticity enables BCR-independent germinal center initiation and antibody affinity maturation
Authors: Silver Jared , Zuo Teng , Chaudhary Neha , Kumari Rupa , Tong Pei , Giguere Sophie , Granato Alessandra , Donthula Rakesh , Devereaux Colby , Wesemann Duane R.
Published: December 2017

Two immunoglobulin (Ig) diversification mechanisms collaborate to provide protective humoral immunity. Combinatorial assembly of IgH and IgL V region exons from gene segments generates preimmune Ig repertoires, expressed as B cell receptors (BCRs). Secondary diversification occurs when Ig V regions undergo somatic hypermutation (SHM) and affinity-based selection toward antigen in activated germinal center (GC) B cells. Secondary diversification is thought to only ripen the antigen-binding affinity of Igs that already exist (i.e., cognate Igs) because of chance generation during preimmune Ig diversification. However, whether stochastic activation of noncognate B cells can generate new affinity to antigen in GCs is unclear. Using a mouse model whose knock-in BCR does not functionally engage with immunizing antigen, we found that chronic immunization induced antigen-specific serological responses with diverse SHM-mediated antibody affinity maturation pathways and divergent epitope targeting. Thus, intrinsic GC B cell flexibility allows for somatic, noncognate B cell evolution, permitting de novo antigen recognition and subsequent antibody affinity maturation without initial preimmune BCR engagement.
The immunology of hypertension
Authors: Norlander Allison E. , Madhur Meena S. , Harrison David G.
Published: December 2017

Although systemic hypertension affects a large proportion of the population, its etiology remains poorly defined. Emerging evidence supports the concept that immune cells become activated and enter target organs, including the vasculature and the kidney, in this disease. Mediators released by these cells, including reactive oxygen species, metalloproteinases, cytokines, and antibodies promote dysfunction of the target organs and cause damage. In vessels, these factors enhance constriction, remodeling, and rarefaction. In the kidney, these mediators increase expression and activation of sodium transporters, and cause interstitial fibrosis and glomerular injury. Factors common to hypertension, including oxidative stress, increased interstitial sodium, cytokine production, and inflammasome activation promote immune activation in hypertension. Recent data suggest that isolevuglandin-modified self-proteins in antigen-presenting cells are immunogenic, promoting cytokine production by the cells in which they are formed and T cell activation. Efforts to prevent and reverse immune activation may prove beneficial in preventing the long-term sequelae of hypertension and its related cardiovascular diseases.
ProbAnnoWeb and ProbAnnoPy: probabilistic annotation and gap-filling of metabolic reconstructions
Authors: King Brendan , Farrah Terry , Richards Matthew A , Mundy Michael , Simeonidis Evangelos , Price Nathan D
Published: December 2017

Gap-filling is a necessary step to produce quality genome-scale metabolic reconstructions capable of flux-balance simulation. Most available gap-filling tools use an organism-agnostic approach, where reactions are selected from a database to fill gaps without consideration of the target organism. Conversely, our likelihood based gap-filling with probabilistic annotations selects candidate reactions based on a likelihood score derived specifically from the target organism’s genome. Here, we present two new implementations of probabilistic annotation and likelihood based gap-filling: a web service called ProbAnnoWeb, and a standalone python package called ProbAnnoPy.

Availability and implementation

Our tools are available as a web service with no installation needed (ProbAnnoWeb) at probannoweb.systemsbiology.net, and as a local python package implementation (ProbAnnoPy) at github.com/PriceLab/probannopy.

Supplementary information

Supplementary data are available at Bioinformatics online.
HTT-DB: new features and updates
Authors: Dotto Bruno Reis , Carvalho Evelise Leis , da Silva Alexandre Freitas , Dezordi Filipe Zimmer , Pinto Paulo Marcos , Campos Tulio de Lima , Rezende Antonio Mauro , Wallau Gabriel da Luz
Published: December 2017

Horizontal Transfer (HT) of genetic material between species is a common phenomenon among Bacteria and Archaea species and several databases are available for information retrieval and data mining. However, little attention has been given to this phenomenon among eukaryotic species mainly due to the lower proportion of these events. In the last years, a vertiginous amount of new HT events involving eukaryotic species was reported in the literature, highlighting the need of a common repository to keep the scientific community up to date and describe overall trends. Recently, we published the first HT database focused on HT of transposable elements among eukaryotes: the Horizontal Transposon Transfer DataBase: Database URL: (http://lpa.saogabriel.unipampa.edu.br: 8080/httdatabase/). Here, we present new features and updates of this unique database: (i) its expansion to include virus-host exchange of genetic material, which we called Horizontal Virus Transfer (HVT) and (ii) the availability of a web server for HT detection, where we implemented the online version of vertical and horizontal inheritance consistence analysis (VHICA), an R package developed for HT detection. These improvements will help researchers to navigate through known HVT cases, take data-informed decision and export figures based on keywords searches. Moreover, the availability of the VHICA as an online tool will make this software easily reachable even for researchers with no or little computation knowledge as well as foster our capability to detect new HT events in a wide variety of taxa.

Database URL: http://lpa.saogabriel.unipampa.edu.br:8080/httdatabase/
L-arginine and Arginase Products Potentiate Dexmedetomidine-induced Contractions in the Rat Aorta
Authors: Wong Emily S. W. , Man Ricky Y. K. , Ng Kwok F. J. , Leung Susan W. S. , Vanhoutte Paul M.
Published: December 2017

Background

The α2-adrenergic sedative/anesthetic agent dexmedetomidine exerts biphasic effects on isolated arteries, causing endothelium-dependent relaxations at concentrations at or below 30 nM, followed by contractions at higher concentrations. l-arginine is a common substrate of endothelial nitric oxide synthase and arginases. This study was designed to investigate the role of l-arginine in modulating the overall vascular response to dexmedetomidine.

Methods

Isometric tension was measured in isolated aortic rings of Sprague Dawley rats. Cumulative concentrations of dexmedetomidine (10 nM to 10 μM) were added to quiescent rings (with and without endothelium) after previous incubation with vehicle, Nω-nitro-l-arginine methyl ester hydrochloride (l-NAME; nitric oxide synthase inhibitor), prazosin (α1-adrenergic antagonist), rauwolscine (α2-adrenergic antagonist), l-arginine, (S)-(2-boronethyl)-l-cysteine hydrochloride (arginase inhibitor), NG-hydroxy-l-arginine (arginase inhibitor), urea and/or ornithine. In some preparations, immunofluorescent staining, immunoblotting, or measurement of urea content were performed.

Results

Dexmedetomidine did not contract control rings with endothelium but evoked concentration-dependent increases in tension in such rings treated with l-NAME (Emax 50 ± 4%) or after endothelium-removal (Emax 74 ± 5%; N = 7 to 12). Exogenous l-arginine augmented the dexmedetomidine-induced contractions in the presence of l-NAME (Emax 75 ± 3%). This potentiation was abolished by (S)-(2-boronethyl)-l-cysteine hydrochloride (Emax 16 ± 4%) and NG-hydroxy-l-arginine (Emax 18 ± 4%). Either urea or ornithine, the downstream arginase products, had a similar potentiating effect as l-arginine. Immunoassay measurements demonstrated an upregulation of arginase I by l-arginine treatment in the presence of l-NAME (N = 4).

Conclusions

These results suggest that when vascular nitric oxide homeostasis is impaired, the potentiation of the vasoconstrictor effect of dexmedetomidine by l-arginine depends on arginase activity and the production of urea and ornithine.
Smartphone Use by Nurses in Acute Care Settings
Authors: Flynn Greir Ander Huck , Polivka Barbara , Behr Jodi Herron
Published: December 2017

The use of smartphones in acute care settings remains controversial due to security concerns and personal use. The purposes of this study were to determine (1) the current rates of personal smartphone use by nurses in acute care settings, (2) nurses' preferences regarding the use of smartphone functionality at work, and (3) nurse perceptions of the benefits and drawbacks of smartphone use at work. An online survey of nurses from six acute care facilities within one healthcare system assessed the use of personal smartphones in acute care settings and perceptions of the benefits and drawbacks of smartphone use at work. Participants (N = 735) were primarily point-of-care nurses older than 31 years. Most participants (98%) used a smartphone in the acute care setting. Respondents perceived the most common useful and beneficial smartphone functions in acute care settings as allowing them to access information on medications, procedures, and diseases. Participants older than 50 years were less likely to use a smartphone in acute care settings and to agree with the benefits of smartphones. There is a critical need for recognition that smartphones are used by point-of-care nurses for a variety of functions and that realistic policies for smartphone use are needed to enhance patient care and minimize distractions.
Postdischarge Light-Intensity Physical Activity Predicts Rehospitalization of Older Japanese Patients With Heart Failure
Authors: Miyahara So , Fujimoto Naoki , Dohi Kaoru , Sugiura Emiyo , Moriwaki Keishi , Omori Taku , Takeuchi Tetsushiro , Kumagai Naoto , Nakamori Shiro , Yamada Norikazu , Ito Masaaki
Published: December 2017

Purpose:

Regular physical activity (PA) is recommended for patients with heart failure (HF). However, the clinical and social characteristics of older HF patients with low-level PA and the impact of light-intensity PA on 6-mo postdischarge adverse cardiovascular events are still unclear.

Methods:

Forty-one older patients who had been admitted because of decompensated HF (American College of Cardiology [ACC]/American Heart Association [AHA] HF classification stage C/D: 76 ± 5 y) were prospectively enrolled. Light-intensity (1.5-2.9 metabolic equivalents [METs]) and moderate-intensity (≥3 METs) PAs were determined by triaxial accelerometry for at least 7 d postdischarge. Six-min walk distance and 36-item Short Form questionnaire (SF-36) score were evaluated at discharge. HF patients were stratified into either the HFPA-high or HFPA-low group according to median daily PA. Twenty-nine older ACC/AHA stage A/B outpatients (HF-risk), who were at risk for HF but no symptoms of HF had developed, also completed these assessments. Clinical predictors for 6-mo postdischarge HF rehospitalization were assessed.

Results:

HF patients were anemic and less active. HFPA-low patients were less likely to engage in household work, took fewer steps, and had less light and moderate-intensity PA than HFPA-high patients. There were no differences in 6-min walk distance, SF-36 score, or left ventricular ejection fraction between HFPA-low and HFPA-high patients. Postdischarge PA, especially light-intensity PA, was independently associated with HF rehospitalization.

Conclusion:

Low volume of PA postdischarge, especially at 1.5 to 2.9 METs, predicts 6-mo postdischarge HF rehospitalization in older HF patients.
Pain or nociception? Subjective experience mediates the effects of acute noxious heat on autonomic responses
Authors: Mischkowski Dominik , Palacios-Barrios Esther E. , Banker Lauren , Dildine Troy C. , Atlas Lauren Y.
Published: December 2017

Nociception reliably elicits an autonomic nervous system (ANS) response. Because pain and ANS circuitry interact on multiple spinal, subcortical, and cortical levels, it remains unclear whether autonomic responses are simply a reflexive product of noxious stimulation regardless of how stimulation is consciously perceived or whether the experience of pain mediates ANS responses to noxious stimulation. To test these alternative predictions, we examined the relative contribution of noxious stimulation and individual pain experience to ANS responses in healthy volunteers who underwent 1 or 2 pain assessment tasks. Participants received 8 seconds of thermal stimulation of varied temperatures and judged pain intensity on every trial. Skin conductance responses and pupil dilation responses to stimulation served as measures of the heat-evoked autonomic response. We used multilevel modelling to examine trial-by-trial relationships between heat, pain, and ANS response. Although both pain and noxious heat stimulation predicted skin conductance response and pupil dilation response in separate analyses, the individual pain experience statistically mediated effects of noxious heat on both outcomes. Furthermore, moderated mediation revealed that evidence for this process was stronger when stimulation was perceived as painful compared with when stimulation was perceived as nonpainful. These findings suggest that pain appraisal regulates the heat-evoked autonomic response to noxious stimulation, documenting the flexibility of the autonomic pain response to adjust to perceived or actual changes in environmental affordances above and beyond nociceptive input.
Extracorporeal Membrane Oxygenation as a Bridge to Lung Transplantation in the United States: A Multicenter Survey
Authors: Tsiouris Athanasios , Budev Marie M. , Yun James J.
Published: December 2017

The clinical use of extracorporeal membrane oxygenation (ECMO) as a bridge to lung transplantation (LTx) has greatly increased in recent years. However, clinical practices for ECMO as a bridge to LTx vary widely between LTx centers. To better define the current practice of ECMO as a bridge to LTx, we surveyed pre-LTx ECMO practices among all adult LTx programs in the United States. All US LTx centers were surveyed (n = 57) between January and December 2014. Responses were received from 33 of 57 centers (58%). Of 33 responding centers, six (18%) performed ≥50 LTxs per year (defined as high volume) and two (6%) performed <10 LTxs per year (low volume). Two-third of responding centers, 22/33 (67%), reported use of ECMO as a bridge to LTx. Of these 22 centers, 18 (82%) successfully used venovenous (VV) ECMO as a bridge to LTx using the dual-lumen Avalon cannula. Patient >65 years of age was judged an ECMO contraindication in 15/33 (45%) of responding centers, but 12/33 (36%) centers, including the six high-volume centers, had no official age cutoff for ECMO candidacy. There was no consensus on the maximum acceptable duration of pre-LTx ECMO therapy; although 18/33 (55%) of programs had no defined maximal duration of ECMO pre-LTx, 10/33 (30%) considered >10 days on ECMO support contraindicated. Our survey suggests that in the United States, ECMO is used frequently pre-LTx, particularly VV ECMO at high-volume centers. However, criteria for ECMO initiation, age eligibility, bedside care, and maximum duration of support varied significantly between survey respondents.
Noninvasive Assessment of Intra-Abdominal Pressure Using Ultrasound-Guided Tonometry: A Proof-of-Concept Study
Authors: Bloch Andreas , Glas Michael , Kohler Andreas , Baumann Ulrich , Jakob Stephan M.
Published: December 2017

Background:

Intra-abdominal hypertension jeopardizes abdominal organ perfusion and venous return. Contemporary recognition of elevated intra-abdominal pressure (IAP) plays a crucial role in reducing mortality and morbidity. We evaluated ultrasound-guided tonometry in this context hypothesizing that the vertical chamber diameter of this device inversely correlates with IAP.

Methods:

IAP was increased in six 5 mmHg steps to 40 mmHg by instillation of normal saline into the peritoneal cavity of eight anesthetized pigs. Liver and renal blood flows (ultrasound transit time), intravesical, intraperitoneal, and end-inspiratory plateau pressures were recorded. For ultrasound-based assessment of IAP (ultrasound-guided tonometry), a pressure-transducing, compressible chamber was fixed at the tip of a linear ultrasound probe, and the system was applied on the abdominal wall using different predetermined levels of external pressure. At each IAP level (reference: intravesical pressure), two investigators measured the vertical diameter of this chamber.

Results:

All abdominal flows decreased (by 39%–58%), and end-inspiratory plateau pressure increased from 15 mbar (14–17 mbar) to 38 mbar (33–42 mbar) (median, range) with increasing IAP (all P < 0.01). Vertical chamber diameter decreased from 14.9 (14.6–15.2) mm to12.8 (12.4–13.4) mm with increasing IAP. Coefficients of variations between and within observers regarding change of the vertical tonometry chamber diameter were small (all <4%), and the results were independent of the externally applied pressure level on the ultrasound probe. Correlation of IAP and vertical pressure chamber distance was highly significant (r = −1, P = 0.0004). Ultrasound-guided tonometry could discriminate between normal (baseline) pressure and 15 mmHg, between 15 and 25 mmHg) and between 25 and 40 mmHg IAP (all P ≤ 0.18). Similar results were obtained for end-inspiratory plateau pressures.

Conclusions:

In our model, values obtained by ultrasound-guided tonometry correlated significantly with IAPs. The method was able to discriminate between normal, moderately, and markedly increased IAP values.
Procalcitonin and Presepsin as Prognostic Markers After Out-of-Hospital Cardiac Arrest
Authors: Pekkarinen Pirkka T. , Ristagno Giuseppe , Wilkman Erika , Masson Serge , Latini Roberto , Laurikkala Johanna , Bendel Stepani , Ala-Kokko Tero , Varpula Tero , Vaahersalo Jukka , Karlsson Sari , Tiainen Marjaana , Mion Monica M. , Plebani Mario , Pettilä Ville , Skrifvars Markus B.
Published: December 2017

Background:

Patients resuscitated from cardiac arrest commonly develop an inflammatory response called post-cardiac arrest syndrome that clinically resembles septic shock.

Procalcitonin and presepsin are associated with inflammation. We hypothesized that these biomarkers reflect the severity of post-cardiac arrest syndrome and predict short-term hemodynamical instability and long-term neurological outcome after cardiac arrest.

Methods:

As a subcohort analysis of a prospective, observational, multicenter study “FINNRESUSCI,” we obtained plasma from 277 intensive care unit (ICU) patients treated following out-of-hospital cardiac arrest (OHCA). Procalcitonin and presepsin levels were measured 0 to 6 h from ICU admission and 24, 48, and 96 h thereafter. We defined poor outcome as a 12-month Cerebral Performance Category of 3 to 5. We tested statistical associations between biomarkers and hemodynamical parameters and outcome with regression models.

Results:

Plasma procalcitonin had best predictive value for 12-month poor outcome at 96 h (AUC 0.76; 95% CI 0.68–0.83) and presepsin at ICU admission (AUC 0.72; 95% CI 0.65–0.78). Elevated procalcitonin concentration at ICU admission predicted unstable hemodynamics in the following 48 h in a linear regression model. In a multivariate logistic regression model with clinical variables, only procalcitonin at 96 h had independent prognostic value for poor 12-month neurological outcome.

Conclusions:

Elevated procalcitonin is associated with hemodynamical instability and worsened long-term outcome in OHCA patients. The association is not strong enough for it to be used as a single predictor. Presepsin did not provide clinically relevant information for risk stratification after OHCA.
Prediction of traumatic carotid-cavernous sinus fistula via noncontrast computed tomography by fracture pattern and abnormality of venous system
Authors: Mao Shih-Hsuan , Lin Tzu-Chin , Chen Chih-Hao , Chou Pang-Yun , Wang Shang-Yu , Wong Yon-Cheong , Chen Chien-Tzung
Published: December 2017

BACKGROUND

Traumatic carotid-cavernous sinus fistula (tCCF) is infrequent but with high morbidity if delayed diagnosed or managed. Because of the lack of screening criteria and requirement of advanced and invasive radiological examinations, diagnosis is often delayed or underdiagnosed.

METHODS

A matched case-control study with univariate and multivariate analyses was conducted to predict tCCFs. Forty-six patients diagnosed with tCCFs were included and matched with 138 patients of craniofacial trauma without tCCF as control at a ratio of 1:3.

RESULTS

The diagnostic diameter of superior ophthalmic vein (SOV) in tCCF was 4 mm with area under curve of 0.89. In multivariate analysis, engorgement of SOV and cavernous sinus (odds ratio [OR], 35.39; 95% confidence interval [CI], 13.56–104.84; p < 0.001) and lateral impact (ipsilateral temporal and sphenoid sinus fractures) (OR, 3.96; 95% CI, 1.10–14.91; p = 0.028) were identified significant, whereas basilar skull fracture (OR, 1.58; 95% CI, 0.53–4.75; p = 0.300) and injuries to ocular nerves (cranial nerves III, IV, and VI) (OR, 1.77; 95% CI, 0.38–7.88; p = 0.055) were insignificant.

CONCLUSION

Presence of SOV or cavernous sinus engorgement on noncontrast computed tomography and lateral impact were demonstrated as independent predictors to tCCF and warrant further radiological evaluation. Injury to ocular nerves is not predictive but as an essential differential diagnosis with reversible outcome.

LEVEL OF EVIDENCE

Diagnostic, level III.
Lower emergency general surgery (EGS) mortality among hospitals with higher-quality trauma care
Authors: Scott John W. , Tsai Thomas C. , Neiman Pooja U. , Jurkovich Gregory J. , Utter Garth H. , Haider Adil H. , Salim Ali , Havens Joaquim M.
Published: December 2017

BACKGROUND

Patients undergoing emergency general surgery (EGS) procedures are up to eight times more likely to die than patients undergoing the same procedures electively. This excess mortality is often attributed to nonmodifiable patient factors including comorbidities and physiologic derangements at presentation, leaving few targets for quality improvement. Although the hospital-level traits that contribute to EGS outcomes are not well understood, we hypothesized that facilities with lower trauma mortality would have lower EGS mortality.

METHODS

Using the Nationwide Inpatient Sample (2008–2011), we calculated hospital-level risk-adjusted trauma mortality rates for hospitals with more than 400 trauma admissions. We then calculated hospital-level risk-adjusted EGS mortality rates for hospitals with more than 200 urgent/emergent admissions for seven core EGS procedures (laparotomy, large bowel resection, small bowel resection, lysis of adhesions, operative intervention for ulcer disease, cholecystectomy, and appendectomy). We used univariable and multivariable techniques to assess for associations between hospital-level risk-adjusted EGS mortality and hospital characteristics, patient-mix traits, EGS volume, and trauma mortality quartile.

RESULTS

Data from 303 hospitals, representing 153,544 admissions, revealed a median hospital-level EGS mortality rate of 1.21% (interquartile range, 0.86%–1.71%). After adjusting for hospital traits, hospital-level EGS mortality was significantly associated with trauma mortality quartile as well as patients’ community income-level and race/ethnicity (p < 0.05 for all). Mean risk-adjusted EGS mortality was 1.09% (95% confidence interval, 0.94–1.25%) at hospitals in the lowest quartile for risk-adjusted trauma mortality, and 1.64% (95% confidence interval, 1.48–1.80%) at hospitals in the highest quartile of trauma mortality (p < 0.01). Sensitivity analyses limited to (1) high-mortality procedures and (2) high-volume facilities; both found similar trends (p < 0.01).

CONCLUSIONS

Patients at hospitals with lower risk-adjusted trauma mortality have a nearly 33% lower risk of mortality after admission for EGS procedures. The structures and processes that improve trauma mortality may also improve EGS mortality. Emergency general surgery–specific systems measures and process measures are needed to better understand drivers of variation in quality of EGS outcomes.

LEVEL OF EVIDENCE

Epidemiological, level III; Care management, level IV.
Reconciling persistent and dynamic hypotheses of working memory coding in prefrontal cortex
Authors: Cavanagh SE , Towers JP , Wallis JD , Hunt LT , Kennerley SW
Published: December 2017

Competing accounts propose that working memory (WM) is subserved either by persistent activity in single neurons or by dynamic (time-varying) activity across a neural population. Here we compare these hypotheses across four regions of prefrontal cortex (PFC) in a spatial WM task, where an intervening distractor indicated the reward available for a correct saccade. WM representations were strongest in ventrolateral PFC (VLPFC) neurons with higher intrinsic temporal stability (time-constant). At the population-level, although a stable mnemonic state was reached during the delay, this tuning geometry was reversed relative to cue-period selectivity, and was disrupted by the distractor. Single-neuron analysis revealed many neurons switched to coding reward, rather than maintaining task-relevant spatial selectivity until saccade. These results imply WM is fulfilled by dynamic, population-level activity within high time-constant neurons. Rather than persistent activity supporting stable mnemonic representations that bridge distraction, PFC neurons may stabilise a dynamic population-level process that supports WM.
Alterations in Cell Motility, Proliferation, and Metabolism in Novel Models of Acquired Temozolomide Resistant Glioblastoma
Authors: Tiek DM , Rone JD , Graham GT , Pannkuk EL , Haddad BR , Riggins RB
Published: December 2017

Glioblastoma (GBM) is an aggressive and incurable tumor of the brain with limited treatment options. Current first-line standard of care is the DNA alkylating agent temozolomide (TMZ), but this treatment strategy adds only ~4 months to median survival due to the rapid development of resistance. While some mechanisms of TMZ resistance have been identified, they are not fully understood. There are few effective strategies to manage therapy resistant GBM, and we lack diverse preclinical models of acquired TMZ resistance in which to test therapeutic strategies on TMZ resistant GBM. In this study, we create and characterize two new GBM cell lines resistant to TMZ, based on the 8MGBA and 42MGBA cell lines. Analysis of the TMZ resistant (TMZres) variants in conjunction with their parental, sensitive cell lines shows that acquisition of TMZ resistance is accompanied by broad phenotypic changes, including increased proliferation, migration, chromosomal aberrations and secretion of cytosolic lipids. Importantly, each TMZ resistant model captures a different facet of the “go” (8MGBA-TMZres) or “grow” (42MGBA-TMZres) hypothesis of GBM behavior. These model systems will be important additions to the available tools for investigators seeking to define molecular mechanisms of acquired TMZ resistance.
An accumulation-of-evidence task using visual pulses for mice navigating in virtual reality
Authors: Pinto Lucas , Koay Sue Ann , Engelhard Ben , Yoon Alice M. , Deverett Ben , Thiberge Stephan Y. , Witten Ilana B. , Tank David W. , Brody Carlos D.
Published: December 2017

The gradual accumulation of sensory evidence is a crucial component of perceptual decision making, but its neural mechanisms are still poorly understood. Given the wide availability of genetic and optical tools for mice, they can be useful model organisms for the study of these phenomena; however, behavioral tools are largely lacking. Here, we describe a new evidence-accumulation task for head-fixed mice navigating in a virtual reality environment. As they navigate down the stem of a virtual T-maze, they see brief pulses of visual evidence on either side, and retrieve a reward on the arm with the highest number of pulses. The pulses occur randomly with Poisson statistics, yielding a diverse yet well-controlled stimulus set, making the data conducive to a variety of computational approaches. A large number of mice of different genotypes were able to learn and consistently perform the task, at levels similar to rats in analogous tasks. They are sensitive to side differences of a single pulse, and their memory of the cues is stable over time. Moreover, using non-parametric as well as modeling approaches, we show that the mice indeed accumulate evidence: they use multiple pulses of evidence from throughout the cue region of the maze to make their decision, albeit with a small overweighting of earlier cues, and their performance is affected by the magnitude but not the duration of evidence. Additionally, analysis of the mice's running patterns revealed that trajectories are fairly stereotyped yet modulated by the amount of sensory evidence, suggesting that the navigational component of this task may provide a continuous readout correlated to the underlying cognitive variables. Our task, which can be readily integrated with state-of-the-art techniques, is thus a valuable tool to study the circuit mechanisms and dynamics underlying perceptual decision making, particularly under more complex behavioral contexts.
Isolation of nucleic acids from low biomass samples: detection and removal of sRNA contaminants
Authors: Heintz-Buschart Anna , Yusuf Dilmurat , Kaysen Anne , Etheridge Alton , Fritz Joëlle V. , May Patrick , de Beaufort Carine , Upadhyaya Bimal B. , Ghosal Anubrata , Galas David J. , Wilmes Paul
Published: December 2017

Background

Sequencing-based analyses of low-biomass samples are known to be prone to misinterpretation due to the potential presence of contaminating molecules derived from laboratory reagents and environments. Due to its inherent instability, contamination with RNA is usually considered to be unlikely.

Results

Here we report the presence of small RNA (sRNA) contaminants in widely used microRNA extraction kits and means for their depletion. Sequencing of sRNAs extracted from human plasma samples was performed and significant levels of non-human (exogenous) sequences were detected. The source of the most abundant of these sequences could be traced to the microRNA extraction columns by qPCR-based analysis of laboratory reagents. The presence of artefactual sequences originating from the confirmed contaminants were furthermore replicated in a range of published datasets. To avoid artefacts in future experiments, several protocols for the removal of the contaminants were elaborated, minimal amounts of starting material for artefact-free analyses were defined, and the reduction of contaminant levels for identification of bona fide sequences using ‘ultraclean’ extraction kits was confirmed.

Conclusion

This is the first report of the presence of RNA molecules as contaminants in laboratory reagents. The described protocols should be applied in the future to avoid confounding sRNA studies.
Leishmania naiffi and Leishmania guyanensis reference genomes highlight genome structure and gene evolution in the Viannia subgenus
Authors: Coughlan Simone , Taylor Ali Shirley , Feane Eoghan , Sanders Mandy , Schonian Gabriele , Cotton James A. , Downing Tim
Published: December 2017

The unicellular protozoan parasite Leishmania causes the neglected tropical disease leishmaniasis, affecting 12 million people in 98 countries. In South America where the Viannia subgenus predominates, so far only L. (Viannia) braziliensis and L. (V.) panamensis have been sequenced, assembled and annotated as reference genomes. Addressing this deficit in molecular information can inform species typing, epidemiological monitoring and clinical treatment. Here, L. (V.) naiffi and L. (V.) guyanensis genomic DNA was sequenced to assemble these two genomes as draft references from short sequence reads. The methods used were tested using short sequence reads for L. braziliensis M2904 against its published reference as a comparison. This assembly and annotation pipeline identified 70 additional genes not annotated on the original M2904 reference. Phylogenetic and evolutionary comparisons of L. guyanensis and L. naiffi with ten other Viannia genomes revealed four traits common to all Viannia: aneuploidy, 22 orthologous groups of genes absent in other Leishmania subgenera, elevated TATE transposon copies, and a high NADH-dependent fumarate reductase gene copy number. Within the Viannia, there were limited structural changes in genome architecture specific to individual species: a 45 Kb amplification on chromosome 34 was present in all bar L. lainsoni, L. naiffi had a higher copy number of the virulence factor leishmanolysin, and laboratory isolate L. shawi M8408 had a possible minichromosome derived from the 3’ end of chromosome 34. This combination of genome assembly, phylogenetics and comparative analysis across an extended panel of diverse Viannia has uncovered new insights into the origin and evolution of this subgenus and can help improve diagnostics for leishmaniasis surveillance.
Prevalence and patterns of higher-order interactions
Authors: Tekin Elif , White Cynthia , Kang Tina Manzhu , Singh Nina , Cruz-Loya Mauricio , Damoiseaux Robert , Savage Van M. , Yeh Pamela J.
Published: December 2017

Interactions and emergent processes are essential for research on complex systems involving many components. Most studies focus solely on pairwise interactions and ignore higher-order interactions among three or more components. To gain deeper insights into higher-order interactions and complex environments, we study antibiotic combinations applied to pathogenicEscherichia coliand obtain unprecedented amounts of detailed data (251 two-drug combinations, 1512 three-drug combinations, 5670 four-drug combinations, and 13608 five-drug combinations). Directly opposite to previous assumptions and reports, we find higher-order interactions increase in frequency with the number of drugs in the bacteria’s environment. Furthermore, we observe a shift towards net synergy (effect greater than expected based on independent individual effects) and towards emergent antagonism (effect less than expected based on lower-order interaction effects). These findings have implications for the potential efficacy of drug combinations and are crucial for better navigating problems associated with the combinatorial complexity of multi-component systems.
Drivers of antimicrobial resistance amongst intestinalEscherichia coliisolated from children in South Asia and sub-Saharan Africa
Authors: Ingle Danielle J. , Levine Myron M. , Kotloff Karen L. , Holt Kathryn E. , Robins-Browne Roy M.
Published: December 2017

Antimicrobial resistance (AMR) dynamics are poorly understood in developing countries, where data on the prevalence of AMR in enteric bacteria are sparse, particularly among children and in the community setting. Here we use a combination of phenotyping, genomics and antimicrobial usage data to investigate patterns of AMR amongst atypical enteropathogenicE. coli(aEPEC) strains isolated from children <5 years old in seven countries (four in sub-Saharan Africa and three in South Asia) over a three-year period. We detected very high rates of AMR, with 65% of isolates displaying resistance to ≥3 drug classes; the rates of AMR were the same amongst strains associated with diarrhea and strains that were carried asymptomatically. Whole genome sequencing identified a diversity of genetic mechanisms for AMR, which could explain >95% of observed phenotypic resistance. Analysis of AMR gene co-occurrence revealed clusters of acquired AMR genes that were frequently co-located on small plasmids and transposons, providing opportunities for acquisition of multidrug resistance in a single step. We used discriminant analysis to investigate potential drivers of AMR within the bacterial population, and found that genetic determinants of AMR were associated with geographical location of isolation but not with phylogenetic lineage of theE. colistrain or disease status of the human host. Comparison with antimicrobial usage data showed that the prevalence of resistance to newer drugs (fluoroquinolones and third-generation cephalosporins) was correlated with usage, which was generally higher in South Asia than Africa. In particular, fluoroquinolone resistance-associated mutations ingyrAwere significantly associated with use of these drugs for treatment of diarrheic children. Notably resistance to older drugs such as trimethoprim, chloramphenicol and ampicillin, which are conferred by acquired AMR genes that were frequently clustered together in mobile genetic elements, were common in all locations despite differences in usage; this suggests that reversion to sensitivity is unlikely to occur even if these drugs are removed from circulation. This study provides much-needed insights into the frequencies of AMR in intestinalE. coliin community-based children in developing countries and to antimicrobial usage for diarrhea where the burden of infections is greatest.
Tracking temporal hazard in the human electroencephalogram using a forward encoding model
Authors: Herbst Sophie K. , Fiedler Lorenz , Obleser Jonas
Published: December 2017

Human observers automatically extract temporal contingencies from the environment and predict the onset of future events. Temporal predictions are modelled by the hazard function, which describes the instantaneous probability for an event to occur given it has not occurred yet. Here, we tackle the question of whether and how the human brain tracks continuous temporal hazard on a moment-to-moment basis, and how flexibly it adjusts to strictly implicit variations in the hazard function. We applied an encoding-model approach to human electroencephalographic (EEG) data recorded during a pitch-discrimination task, in which we implicitly manipulated temporal predictability of the target tones by varying the interval between cue and target tone (the foreperiod). Critically, temporal predictability was either solely driven by the passage of time (resulting in a monotonic hazard function), or was modulated to increase at intermediate foreperiods (resulting in a modulated hazard function with a peak at the intermediate foreperiod). Forward encoding models trained to predict the recorded EEG signal from different temporal hazard functions were able to distinguish between experimental conditions, showing that implicit variations of temporal hazard bear tractable signatures in the human electroencephalogram. Notably, this tracking signal was reconstructed best from the supplementary motor area (SMA), underlining this area’s link to cognitive processing of time. Our results underline the relevance of temporal hazard to cognitive processing, and show that the predictive accuracy of the encoding-model approach can be utilised to track abstract time-resolved stimuli.

Significance Statement

Extracting temporal predictions from sensory input allows to process future input more efficiently and to prepare responses in time. In mathematical terms, temporal predictions can be described by the hazard function, modelling the probability of an event to occur over time. Here, we show that the human EEG tracks temporal hazard in an implicit foreperiod paradigm. Forward encoding models trained to predict the recorded EEG signal from different temporal-hazard functions were able to distinguish between experimental conditions that differed in their build-up of hazard over time. These neural signatures of tracking temporal hazard converge with the extant literature on temporal processing and provide new evidence that the supplementary motor area tracks hazard under strictly implicit timing conditions.
Glucocorticoid receptor-mediated amygdalar metaplasticity underlies adaptive modulation of fear memory by stress
Authors: Inoue Ran , Abdou Kareem , Hayashi-Tanaka Ayumi , Muramatsu Shin-ichi , Mino Kaori , Inokuchi Kaoru , Mori Hisashi
Published: December 2017

Glucocorticoid receptor (GR) is crucial for signaling mediated by stress-induced high levels of glucocorticoids. The lateral nucleus of the amygdala (LA) is a key structure underlying auditory-cued fear conditioning. Here, we demonstrate that genetic disruption of GR in the LA (LAGRKO) resulted in an auditory-cued fear memory deficit for strengthened conditioning. Furthermore, the suppressive effect of a single restraint stress (RS) prior to conditioning on auditory-cued fear memory in floxed GR (control) mice was abolished in LAGRKO mice. Optogenetic induction of long-term depression (LTD) at auditory inputs to the LA reduced auditory-cued fear memory in RS-exposed LAGRKO mice, and in contrast, optogenetic induction of long-term potentiation (LTP) increased auditory-cued fear memory in RS-exposed floxed GR mice. These findings suggest that prior stress suppresses fear conditioning-induced LTP at auditory inputs to the LA in a GR-dependent manner, thereby protecting animals from encoding excessive cued fear memory under stress conditions.
Simultaneous Estimation of Population Receptive Field and Hemodynamic Parameters from Single Point BOLD Responses using Metropolis-Hastings Sampling
Authors: Adaszewski Stanisław , Slater David , Melie-Garcia Lester , Draganski Bogdan , Bogorodzki Piotr
Published: December 2017

We introduce a new approach to Bayesian pRF model estimation using Markov Chain Monte Carlo (MCMC) sampling for simultaneous estimation of pRF and hemodynamic parameters. To obtain high performance on commonly accessible hardware we present a novel heuristic consisting of interpolation between precomputed responses for predetermined stimuli and a large cross-section of receptive field parameters. We investigate the validity of the proposed approach with respect to MCMC convergence, tuning and biases. We compare different combinations of pRF - Compressive Spatial Summation (CSS), Dumoulin-Wandell (DW) and hemodynamic (5-parameter and 3-parameter Balloon-Windkessel) models within our framework with and without the usage of the new heuristic. We evaluate estimation consistency and log probability across models. We perform as well a comparison of one model with and without lookup table within the RStan framework using its No-U-Turn Sampler. We present accelerated computation of whole-ROI parameters for one subject. Finally, we discuss risks and limitations associated with the usage of the new heuristic as well as the means of resolving them. We found that the new algorithm is a valid sampling approach to joint pRF/hemodynamic parameter estimation and that it exhibits very high performance.