bluuebunny/crossref_metadata_2025 huggingface dataset:
Nasal Bone Osteoma Approach
Authors: Ono Maria Cecília Closs , D’Avanço de Morais André , Freitas Renato da Silva
Published: October 2019

Osteoma is a benign osteogenic lesion that arises most frequently in the craniomaxillofacial region. Rarely, it can appear on the outer side of nasal bone and cause aesthetic problems. The authors present an unusual case of outer side nasal bone osteoma with a brief review of its main clinical presentations, diagnostic studies, and treatment options.
Health Care Spending and New Persistent Opioid Use After Surgery
Authors: Lee Jay S. , Vu Joceline V. , Edelman Anthony L. , Gunaseelan Vidhya , Brummett Chad M. , Englesbe Michael J. , Waljee Jennifer F.
Published: October 2019

Objective:

We sought to describe the differences in health care spending and utilization among patients who develop persistent postoperative opioid use.

Summary of Background Data:

Although persistent opioid use following surgery has garnered concern, its impact on health care costs and utilization remains unknown.

Methods:

We examined insurance claims among 133,439 opioid-naive adults undergoing surgery. Outcomes included 6-month postoperative health care spending; proportion of spending attributable to admission, readmission, ambulatory or emergency care; monthly spending 6 months before and following surgery. We defined persistent opioid use as continued opioid fills beyond 3 months postoperatively. We used linear regression to estimate outcomes adjusting for clinical covariates.

Results:

In this cohort, 8103 patients developed persistent opioid use. For patients who underwent inpatient procedures, new persistent opioid use was associated with health care spending (+$2700 per patient, P < 0.001) compared with patients who did not develop new persistent use. For patients who underwent outpatient procedures, new persistent opioid use was similarly correlated with higher health care spending (+$1500 per patient, P < 0.001) compared with patients who did not develop new persistent use. Patients without persistent opioid use returned to baseline health care spending within 6 months, regardless of other complications. However, patients with persistent opioid use had sustained increases in spending by approximately $200 per month.

Conclusion:

Unlike other postoperative complications, persistent opioid use is associated with sustained increases in spending due to greater readmissions and ambulatory care visits. Early identification of patients vulnerable to persistent use may enhance the value of surgical care.
Prediction Model of Long-term Survival After Esophageal Cancer Surgery
Authors: Xie Shao-Hua , Santoni Giola , Mälberg Kalle , Lagergren Pernilla , Lagergren Jesper
Published: October 2019

Objective:

We aimed to develop prediction models for estimating the long-term survival in patients who have undergone surgery for esophageal cancer.

Background:

Few prediction models have been developed for the long-term survival in esophageal cancer patients.

Methods:

This nationwide Swedish population-based cohort study included 1542 patients who survived for ≥90 days after esophageal cancer surgery between 1987 and 2010, with follow-up until 2016. Risk prediction models for 1-, 3-, and 5-year all-cause mortality and 3- and 5-year disease-specific mortality were developed using logistic regression. Candidate predictors were established and readily identifiable prognostic factors. The performance of the models was assessed by the area under receiver-operating characteristic curve (AUC) with interquartile range (IQR) using bootstrap cross-validation and risk calibration.

Results:

Predictors included in all models were age, sex, pathological tumor stage, tumor histology, and resection margin status. The models also included various additional predictors depending on the outcome, that is, education level, neoadjuvant therapy, reoperation (within 30 d of primary surgery) and comorbidity (Charlson comorbidity index). The AUC statistics after cross-validation were 0.71 (IQR 0.69–0.74) for 1-year, 0.77 (IQR 0.75–0.80) for 3-year, and 0.78 (IQR 0.76–0.81) for 5-year all-cause mortality. The corresponding values were 0.76 (IQR 0.74–0.79) for 3-year and 0.77 (IQR 0.71–0.83) for 5-year disease-specific mortality. All models showed good agreement between the observed and predicted risks.

Conclusions:

These models showed good performance for predicting long-term survival after esophageal cancer surgery and may thus be useful for patients in planning their lives and to guide the postoperative treatment and follow-up.
Prophylactic Negative Pressure Wound Therapy for Closed Laparotomy Incisions
Authors: Kuper Tanya M. , Murphy Patrick B. , Kaur Bandeep , Ott Michael C.
Published: October 2019

Objective:

The aim of this study was to determine whether negative pressure wound therapy (NPWT) applied to primarily closed incisions decreases surgical site infections (SSIs) following open abdominal surgery.

Background:

SSIs are a common cause of morbidity following open abdominal surgery. Prophylactic NPWT has shown promise for SSI reduction. However, the results of randomized controlled trials (RCTs) conducted among patients undergoing laparotomy have been inconsistent.

Methods:

We performed a meta-analysis of English language RCTs comparing the use of prophylactic NPWT to standard dressings on primarily closed laparotomy incisions following open abdominal surgery. Medline, EMBASE, Cochrane Library, and CINAHL databases were searched from inception to December 31st, 2018, for relevant studies. A random-effects model was used for statistical analysis.

Results:

Five RCTs totaling 792 patients were included in our meta-analysis after application of our exclusion and inclusion criteria. There was no significant difference in the risk of SSIs identified among those patients who had NPWT compared to standard dressings; relative risk (RR) 0.56 (95% confidence interval 0.30–1.03, P = 0.064). There was significant statistical heterogeneity across studies (I
2 = 67.4%; P = 0.015).

Conclusion:

The adoption of NPWT for routine SSI prophylaxis following laparotomy is currently not supported and should be used primarily in the context of a clinical trial.
Early Versus Delayed Surgical Repair and Referral for Patients With Bile Duct Injury
Authors: Wang Xiang , Yu Wen-Long , Fu Xiao-Hui , Zhu Bin , Zhao Teng , Zhang Yong-Jie
Published: October 2019

Objective:

The aim of the study was to systematically review and meta-analyze the available evidence regarding the association between timing of repair or referral and clinical outcomes in bile duct injury (BDI).

Background:

Surgical repair is recommended for patients with complex BDI following laparoscopic cholecystectomy. However, consensus on the timing of surgery or referral to a specialist is lacking.

Methods:

We searched PubMed, Embase, Cochrane Library, and Scopus for eligible studies. The coprimary outcomes were repair failure in follow-up and postoperative complications. We pooled odds ratios (ORs) using random-effects models.

Results:

We included 32 studies. The rate of repair failure was significantly higher for early versus delayed repair [OR 1.65, 95% confidence interval (CI) 1.14–2.37, P
= 0.007], lower for early versus delayed referral (OR 0.28, 95% CI 0.17–0.45, P < 0.001), but did not differ substantially for on-table versus postcholecystectomy repair (OR 2.06, 95% CI 0.89–4.73, P = 0.09). Regarding postoperative complications, early referral outperformed delayed referral (OR 0.24, 95% CI 0.09–0.68, P
= 0.007); however, we found no significant differences between early and delayed repair (OR 1.34, 95% CI 0.96–1.87, P
= 0.08), or between on-table and postcholecystectomy repair (OR 1.13, 95% CI 0.42–3.07, P
= 0.81). At the cutoff time point of 6 weeks, early repair was associated with increased rates of repair failure (OR 4.03; P < 0.001), postoperative complications (OR 2.18; P < 0.001), and biliary stricture (OR 6.23; P < 0.001).

Conclusions:

Among patients with BDI, early referral and delayed repair appear to confer favorable outcomes.
Innovation and Tribulation in the History of Randomized Controlled Trials in Surgery
Authors: Bothwell Laura E. , Jones David S.
Published: October 2019

Despite persistent critiques of the rigor of surgical research, surgeons have actually pursued careful empirical studies for centuries. Their work has enriched not only surgical science but also the development of evidencebased medicine. From conducting landmark controlled trials, to using statistics, alternate patient allocation, randomization, and sham controls, surgeons have long embraced innovative trial approaches and played important roles in the development of key methods of RCTs. However, historical contexts unique to surgery have shaped the implementation of RCTs in this field. Unlike the history of pharmaceuticals, in which substantial research funding has been devoted to testing new drugs before their approval, surgical trials have followed a different trajectory. New operations have repeatedly come into wide use in the absence of RCTs. On many occasions, when established procedures have become controversial, surgeons have then marshaled the resources to conduct RCTs reassessing the operations. Such trials have triggered powerful debates in which proponents of surgical RCTs battled against ingrained practices and preferences. In such cases, RCTs often were not decisive factors in determining the fate of surgical practices but supporting tools that followed and reflected changes in surgical judgment already underway. Surgical trialists also have encountered specific, recurring challenges, especially with the methodological and ethical complexity of blinded and sham-controlled trials. The history of surgical trials thus reveals major contributions from surgeons to the advancement of evidence-based medicine, as well as ongoing challenges. Strengthened and systematic trial support could advance the future of surgical RCTs.
Changes in Hospital-acquired Conditions and Mortality Associated With the Hospital-acquired Condition Reduction Program
Authors: Arntson Emily , Dimick Justin B. , Nuliyalu Ushapoorna , Errickson Josh , Engler Tedi A. , Ryan Andrew M.
Published: October 2019

Importance:

To improve patient safety, the Centers for Medicare and Medicaid Services announced the Hospital-Acquired Condition Reduction Program (HACRP) in August 2013. The program reduces Medicare payments by 1% for hospitals in the lowest performance quartile related to hospital-acquired conditions. Performance measures are focused on perioperative care.

Objective:

To evaluate changes in HACs and 30-day mortality after the announcement of the HACRP.

Design:

Interrupted time-series design using Medicare Provider and Analysis Review (MEDPAR) claims data. We estimated models with linear splines to test for changes in HACs and 30-day mortality before the Affordable Care Act (ACA), after the ACA, and after the HACRP.

Setting:

Fee-for-service Medicare 2009–2015.

Participants:

Medicare beneficiaries undergoing surgery and discharged from an acute care hospital between January 2009 and August 2015 (N = 8,857,877).

Main Outcome and Measure:

Changes in HACs and 30-day mortality after the announcement of the HACRP.

Results:

Patients experienced HACs at a rate of 13.39 per 1000 discharges [95% confidence interval (CI), 13.10 to 13.68] in the pre-ACA period. This declined after the ACA was passed and declined further after the HACRP announcement [adjusted difference in annual slope, −1.34 (95% CI, −1.64 to −1.04)]. Adjusted 30-day mortality was 3.69 (95% CI, 3.64 to 3.74) in the pre-ACA period among patients receiving surgery. Thirty-day mortality continued to decline after the ACA [adjusted annual slope −0.04 (95% CI, −0.05 to −0.02)] but was flat after the HACRP [adjusted annual slope −0.01 (95% CI, −0.04 to 0.02)].

Conclusions and Relevance:

Although hospital-acquired conditions targeted under the HACRP declined at a greater rate after the program was announced, 30-day mortality was unchanged.
Frailty Factors and Outcomes in Vascular Surgery Patients
Authors: Houghton John S. M. , Nickinson Andrew T. O. , Morton Alastair J. , Nduwayo Sarah , Pepper Coral J. , Rayt Harjeet S. , Gray Laura J. , Conroy Simon P. , Haunton Victoria J. , Sayers Rob D.
Published: October 2019

Objective:

To describe and critique tools used to assess frailty in vascular surgery patients, and investigate its associations with patient factors and outcomes.

Background:

Increasing evidence shows negative impacts of frailty on outcomes in surgical patients, but little investigation of its associations with patient factors has been undertaken.

Methods:

Systematic review and meta-analysis of studies reporting frailty in vascular surgery patients (PROSPERO registration: CRD42018116253) searching Medline, Embase, CINAHL, PsycINFO, and Scopus. Quality of studies was assessed using Newcastle–Ottawa scores (NOS) and quality of evidence using Grading of Recommendations Assessment, Development, and Evaluation criteria. Associations of frailty with patient factors were investigated by difference in means (MD) or expressed as risk ratios (RRs), and associations with outcomes expressed as odds ratios (ORs) or hazard ratios (HRs). Data were pooled using random-effects models.

Results:

Fifty-three studies were included in the review and only 8 (15%) were both good quality (NOS ≥ 7) and used a well-validated frailty measure. Eighteen studies (62,976 patients) provided data for the meta-analysis. Frailty was associated with increased age [MD 4.05 years; 95% confidence interval (CI) 3.35, 4.75], female sex (RR 1.32; 95% CI 1.14, 1.54), and lower body mass index (MD −1.81; 95% CI −2.94, −0.68). Frailty was associated with 30-day mortality [adjusted OR (AOR) 2.77; 95% CI 2.01–3.81), postoperative complications (AOR 2.16; 95% CI 1.55, 3.02), and long-term mortality (HR 1.85; 95% CI 1.31, 2.62). Sarcopenia was not associated with any outcomes.

Conclusion:

Frailty, but not sarcopenia, is associated with worse outcomes in vascular surgery patients. Well-validated frailty assessment tools should be preferred clinically, and in future research.
Specific challenges in end-of-life care for patients with hematological malignancies
Authors: Gerlach Christina , Alt-Epping Bernd , Oechsle Karin
Published: October 2019

Purpose of review

The disease-related burden of patients with hematological malignancies is comparable with patients suffering from solid tumors. Palliative care offers relief from suffering independent of type of disease and prognosis. The prevalence of hematological malignancies is expected to increase in the next 20 years because of better therapeutic options with longer survival and because of the aging population. However, patients with hematological malignancies are underrepresented in palliative care as these diseases are associated with special care needs and prognostic uncertainty, which differ from the unambiguity of terminally ill patients with solid tumors. This review describes the recent studies and guidelines addressing the problems in palliative care for patients with hematological malignancies.

Recent findings

Recent research covers prognostic uncertainty, challenges in terms of the acute death setting, and blood transfusions in the terminally ill as well as interdisciplinary collaboration. In addition to qualitative approaches exploring reasons for these challenges, criteria that indicate the approaching end of life in hematological malignancies were systematically developed and tested. Further, the effectiveness of palliative care addressing the hematopoietic stem cell transplantation setting was further analyzed.

The patients’ perspective needs to be involved in future research to examine whether the connotation of ‘palliative care’ is a barrier for patients, families or healthcare professionals. Communication culture and skills have already been identified as goals for medical training. Further studies should identify the effective elements of palliative care specific for hematological malignancies and develop feasible support models, including informal caregivers.
The Association Between Cytomegalovirus Infection and Cardiac Allograft Vasculopathy in the Era of Antiviral Valganciclovir Prophylaxis
Authors: Klimczak-Tomaniak Dominika , Roest Stefan , Brugts Jasper J. , Caliskan Kadir , Kardys Isabella , Zijlstra Felix , Constantinescu Alina A. , Voermans Jolanda J.C. , van Kampen Jeroen J.A. , Manintveld Olivier C.
Published: October 2019

Background.

Previous studies on the association between cytomegalovirus (CMV) infection and cardiac allograft vasculopathy (CAV) were conducted on patients transplanted in the prevalganciclovir prophylaxis era. The aim of our study is to evaluate this relation in heart transplantation (HTx) recipients treated according to current prophylactic and immunosuppressive regimens.

Methods.

This single-center retrospective study included all consecutive adult patients that underwent HTx between January 1, 2000, and May 31, 2018. Clinically relevant CMV infection was defined as either plasma CMV DNAemia ≥ 1000 IU/mL with/without clinical symptoms or <1000 IU/mL with symptoms. The primary endpoint was first manifestation of CAV diagnosed by coronary angiography. For statistical analysis, the cause-specific hazard regression model was applied, with clinically relevant CMV infection and any CMV infection as time-dependent variables.

Results.

In total, 260 patients were included in the analysis. The median (interquartile range) follow-up was 7.88 (4.21–12.04) years. During the follow-up, clinically relevant CMV infection was diagnosed in 96 (37%) patients and CAV in 149 (57%) patients. In the multivariate regression analysis, independent predictors of CAV were: number of rejection episodes (cause-specific hazard ratio [95% confidence interval]: 1.18 [1.04-1.34], P = 0.01), hypertension (1.61 [1.11-2.34], P = 0.01), treatment with mycophenolate mofetil (0.68 [0.47-0.97], P = 0.03). No significant association was observed between CMV infection and CAV, except for patients who experienced a breakthrough CMV infection (n = 24) during prophylaxis (1.94 [1.11-3.40], P = 0.02).

Conclusions.

In the era of contemporary immunosuppression and valganciclovir prophylaxis, a significant effect of CMV infection on the risk of CAV was seen only among HTx recipients with CMV breakthrough infection.
Balancing Efficiency and Fairness in Liver Transplant Access: Tradeoff Curves for the Assessment of Organ Distribution Policies
Authors: Bertsimas Dimitris , Papalexopoulos Theodore , Trichakis Nikolaos , Wang Yuchen , Hirose Ryutaro , Vagefi Parsia A.
Published: October 2019

Background.

Current distribution policies have resulted in persistent geographic disparity in access to donated livers across the country for waitlisted candidates.

Methods.

Using mathematical optimization, and subsequently the Liver Simulation Allocation Model, the following organ distribution concepts were assessed: (1) current policy, (2) proposed alternative models, and (3) a novel continuous distribution model. A number of different scenarios for each policy distribution concept were generated and analyzed through efficiency-fairness tradeoff curves.

Results.

The continuous distribution concept allowed both for the greatest reduction in patient deaths and for the most equitable geographic distribution across comparable organ transportation burden. When applied with an Optimized Prediction of Mortality allocation scheme, continuous distribution allowed for a significant reduction in number of deaths—on the order of 500 lives saved annually (https://livervis.github.io/).

Conclusions.

Tradeoff curves allow for a visualized understanding on the efficiency/fairness balance, and have demonstrated that liver candidates awaiting transplant would benefit from a model employing continuous distribution as this holds the greatest advantage for mortality reduction. Development and implementation of continuous distribution models for all solid organ transplants may allow for minimization of the geographic disparity in organ distribution, and allow for efficient and fair access to a limited national resource for all candidates.
Use of De Novo mTOR Inhibitors in Hypersensitized Kidney Transplant Recipients: Experience From Clinical Practice
Authors: Cucchiari David , Molina-Andujar Alicia , Montagud-Marrahi Enrique , Revuelta Ignacio , Rovira Jordi , Ventura-Aguiar Pedro , Piñeiro Gastón J. , De Sousa-Amorim Erika , Esforzado Nuria , Cofán Frederic , Torregrosa Jose-Vicente , Ugalde-Altamirano Jessica , Ricart M. José , Centellas-Pérez Francisco J. , Solè Manel , Martorell Jaume , Ríos José , Campistol Josep M. , Diekmann Fritz , Oppenheimer Frederic
Published: October 2019

Background.

It is commonly believed that mTOR inhibitors (mTORi) should not be used in high-immunological risk kidney transplant recipients due to a perceived increased risk of rejection. However, almost all trials that examined the association of optimal-dose mTORi with calcineurin inhibitor (CNI) have excluded hypersensitized recipients from enrollment.

Methods.

To shed light on this issue, we examined 71 consecutive patients with a baseline calculated panel reactive antibody (cPRA) ≥50% that underwent kidney transplantation from June 2013 to December 2016 in our unit. Immunosuppression was based on CNI (tacrolimus), steroids and alternatively mycophenolic acid (MPA; n = 38), or mTORi (either everolimus or sirolimus, n = 33, target trough levels 3–8 ng/mL).

Results.

Demographic and immunological risk profiles were similar, and almost 90% of patients in both groups received induction with lymphocyte-depleting agents. Cox-regression analysis of rejection-free survival revealed better results for mTORi versus MPA in terms of biopsy-proven acute rejection (hazard ratio [confidence interval], 0.32 [0.11-0.90],P= 0.031 at univariable analysis and 0.34 [0.11-0.95],P= 0.040 at multivariable analysis). There were no differences in 1-year renal function, Banff chronicity score at 3- and 12-month protocol biopsy and development of de novo donor-specific antibodies. Tacrolimus trough levels along the first year were not different between groups (12-mo levels were 8.72 ± 2.93 and 7.85 ± 3.07 ng/mL for MPA and mTORi group respectively,P= 0.277).

Conclusions.

This single-center retrospective cohort analysis suggests that in hypersensitized kidney transplant recipients receiving tacrolimus-based immunosuppressive therapy similar clinical outcomes may be obtained using mTOR inhibitors compared to mycophenolate.
The relationship between resting electroencephalogram oscillatory abnormalities and schizotypal personality traits in the first-degree relatives of schizophrenia patients
Authors: Chen Chen , Huang Wei , Chen Xianjun , Shi Xiufang , Zhu Xiquan , Ma Wentao , Wang Yapei , Kang Qi , Wang Xiuchao , Guan Muzhen , Huang He , Wu Shengjun , Liu Xufeng
Published: October 2019

Although a large amount of studies have manifested resting state electroencephalogram oscillatory abnormalities in schizophrenia and their first-degree relatives and in schizotype, the results are far from consistent and no research found any relationship between electroencephalograph (EEG) abnormalities and schizotypal personality in first-degree relatives. The present study is to verify the modifications of EEG power spectra in eyes-open resting state of schizophrenia and first-degree relatives, and to investigate associations between EEG band power and schizotypal personality traits in first-degree relatives of schizophrenia patients. Participant samples in this study consisted of 33 healthy normal controls, 35 unaffected first-degree relatives of schizophrenia patients and 35 schizophrenia patients. Group differences in resting EEG band power were examined via repeated-measures analysis of variance, and correlation between EEG power and schizotypal personality traits via Pearson Correlation analysis. The results showed that patients with schizophrenia exhibited increased delta, theta and alpha activity over anterior and central regions in eyes-open resting state compared with that of normal control. Gamma band power was found for the first time to be negatively correlated to schizotypal personality traits in first-degree relatives of schizophrenia patients. To conclusion, these findings suggested that low-frequency EEG activity might be neural manifestations of pathophysiological changes in the brain of schizophrenia, and gamma band activity might be an approach to measure the genetic liability of the disorder.
The two oxpecker species reveal the role of movement rates and foraging intensity in species coexistence
Authors: Péron Guillaume , Bonenfant Christophe , Gagnon Roxanne , Mabika Cheryl T.
Published: October 2019

The two
Buphagus
oxpecker species are specialized passerines that forage for ticks and other food particles on the body of ungulates in the African savannahs. One of their intriguing features is their ability to coexist despite sharing the same, specialized diet. Using co-occurrence data (photographs of giraffes with oxpeckers on them) and approximate Bayesian computing, we demonstrate that yellow-billed oxpeckers changed host faster than red-billed oxpeckers and appeared to displace red-billed oxpeckers from preferred giraffe body parts. Conversely, red-billed oxpeckers exhibited a fuller use of each host and displaced yellow-billed oxpeckers from distal giraffe body parts. These findings highlight that the partition of giraffe hosts in two separate niches was only part of the coexistence story in this species pair. More precisely, the oxpeckers shared the resource by exploiting it at different rates. They engaged in different trade-offs between giving-up density, patch discovery rate and competitor displacement ability. They illustrate the importance of the time frame of interactions.
Expression analyses of cave mollies (
Poecilia mexicana
) reveal key genes involved in the early evolution of eye regression
Authors: McGowan Kerry L. , Passow Courtney N. , Arias-Rodriguez Lenin , Tobler Michael , Kelley Joanna L.
Published: October 2019

Eye regression occurs across cave-dwelling populations of many species and is often coupled with a decrease or loss in eye function. Teleost fishes are among the few vertebrates to undergo widespread colonization of caves and often exhibit eye regression with blindness. Cave populations of the poeciliid fish
Poecilia mexicana
(cave molly) exhibit reduced—albeit functional—eyes, offering the opportunity to investigate partial eye regression. We sequenced eye transcriptomes of cave and surface populations of
P. mexicana
to identify differentially expressed genes that potentially underlie eye regression in cave mollies. We identified 28 significantly differentially expressed genes, 20 of which were directly related to light sensitivity, eye structure and visual signaling. Twenty-six of these genes were downregulated in cave compared to surface populations. Functional enrichment analysis revealed eye-related gene ontologies that were under-represented in cave mollies. In addition, a set of co-expressed genes related to vision and circadian rhythm was correlated with habitat type (cave versus surface). Our study suggests that differential gene expression plays a key role in the beginning evolutionary stages of eye regression in
P. mexicana
, shedding further light on regressive evolution in cavefish.
Earlier colony arrival but no trend in hatching timing in two congeneric seabirds (Uriaspp.) across the North Atlantic
Authors: Merkel Benjamin , Descamps Sébastien , Yoccoz Nigel G. , Danielsen Jóhannis , Daunt Francis , Erikstad Kjell E. , Ezhov Aleksey V. , Grémillet David , Gavrilo Maria , Lorentsen Svein-Håkon , Reiertsen Tone K. , Steen Harald , Systad Geir H. , Þórarinsson Þorkell Lindberg , Wanless Sarah , Strøm Hallvard
Published: October 2019

A global analysis recently showed that seabird breeding phenology (as the timing of egg-laying and hatching) does not, on average, respond to temperature changes or advance with time (Keoganet al.2018Nat. Clim. Change8, 313–318). This group, the most threatened of all birds, is therefore prone to spatio-temporal mismatches with their food resources. Yet, other aspects of the breeding phenology may also have a marked influence on breeding success, such as the arrival date of adults at the breeding site following winter migration. Here, we used a large tracking dataset of two congeneric seabirds breeding in 14 colonies across 18° latitudes, to show that arrival date at the colony was highly variable between colonies and species (ranging 80 days) and advanced 1.4 days/year while timing of egg-laying remained unchanged, resulting in an increasing pre-laying duration between 2009 and 2018. Thus, we demonstrate that potentially not all components of seabird breeding phenology are insensitive to changing environmental conditions.
The limits of Chemistry: how William Gregory contested the boundaries of ‘established science’, 1820–1850
Authors: Packham Ellen
Published: October 2019

In this paper, I examine the controversial career of William Gregory (1803–1858). As a chemistry professor and chemical author, Gregory made many attempts to redefine the bounds of chemical science to incorporate mesmerism, phrenology and animal magnetism. I use a series of letters between Gregory and the prominent phrenologist George Combe to highlight the fact that the definition of ‘established science’ and its disciplinary boundaries were matters that occupied the thoughts and affected the careers of both men. Gregory maintained his reputation as a chemist while simultaneously being ridiculed for his public promotion of phrenology, mesmerism and animal magnetism. Where previous scholarship has tended to separate Gregory's chemical work from his support for disputed phenomena, this paper aims to prove that, for Gregory and his contemporaries, work on mesmerism, animal magnetism and phrenology was methodologically inseparable from chemical work. Gregory argued that all facts and theories should be judged and debated using the same criteria for credibility, accuracy, scepticism and rigour. He and others pushed to include contested phenomena within the boundaries of science to ensure that the facts, controversies and theories relating to them could be subjected to the same rigorous investigation and legitimate debates as were expected of chemical facts and theories.
Cellular sensing of micron-scale curvature: a frontier in understanding the microenvironment
Authors: Assoian Richard K. , Bade Nathan D. , Cameron Caroline V. , Stebe Kathleen J.
Published: October 2019

The vast majority of cell biological studies examine function and molecular mechanisms using cells on flat surfaces: glass, plastic and more recently elastomeric polymers. While these studies have provided a wealth of valuable insight, they fail to consider that most biologically occurring surfaces are curved, with a radius of curvature roughly corresponding to the length scale of cells themselves. Here, we review recent studies showing that cells detect and respond to these curvature cues by adjusting and re-orienting their cell bodies, actin fibres and nuclei as well as by changing their transcriptional programme. Modelling substratum curvature has the potential to provide fundamental new insight into cell behaviour and functionin vivo.
Segregation and polarization in urban areas
Authors: Morales Alfredo J. , Dong Xiaowen , Bar-Yam Yaneer , ‘Sandy’ Pentland Alex
Published: October 2019

Social behaviours emerge from the exchange of information among individuals—constrained by and reciprocally influencing the structure of information flows. The Internet radically transformed communication by democratizing broadcast capabilities and enabling easy and borderless formation of new acquaintances. However, actual information flows are heterogeneous and confined to self-organized echo-chambers. Of central importance to the future of society is understanding how existing physical segregation affects online social fragmentation. Here, we show that the virtual space is a reflection of the geographical space where physical interactions and proximity-based social learning are the main transmitters of ideas. We show that online interactions are segregated by income just as physical interactions are, and that physical separation reflects polarized behaviours beyond culture or politics. Our analysis is consistent with theoretical concepts suggesting polarization is associated with social exposure that reinforces within-group homogenization and between-group differentiation, and they together promote social fragmentation in mirrored physical and virtual spaces.
Attractiveness of thermally different, uniformly black targets to horseflies:Tabanus tergestinusprefers sunlit warm shiny dark targets
Authors: Horváth Gábor , Pereszlényi Ádám , Tóth Tímea , Polgár Szabolcs , Jánosi Imre M.
Published: October 2019

From a large distance tabanid flies may find their host animal by means of its shape, size, motion, odour, radiance and degree of polarization of host-reflected light. After alighting on the host, tabanids may use their mechano-, thermo-, hygro- and chemoreceptors to sense the substrate characteristics. Female tabanids prefer to attack sunlit against shady dark host animals, or dark against bright hosts for a blood meal, the exact reasons for which are unknown. Since sunlit darker surfaces are warmer than shady ones or sunlit/shady brighter surfaces, the differences in surface temperatures of dark and bright as well as sunlit and shady hosts may partly explain their different attractiveness to tabanids. We tested this observed warmth preference in field experiments, where we compared the attractiveness to tabanids (Tabanus tergestinus) of a warm and a cold shiny black barrel imitating dark hosts with the same optical characteristics. Using imaging polarimetry, thermography and Schlieren imaging, we measured the optical and thermal characteristics of both barrels and their small-scale models. We recorded the number of landings on these targets and measured the time periods spent on them. Our study revealed thatT. tergestinustabanid flies prefer sunlit warm shiny black targets against sunlit or shady cold ones with the same optical characteristics. These results support our new hypothesis that a blood-seeking female tabanid prefers elevated temperatures, partly because her wing muscles are more rapid and her nervous system functions better (due to faster conduction velocities and synaptic transmission of signals) in a warmer microclimate, and thus, she can avoid the parasite-repelling reactions of host animals by a prompt take-off.
Interactions between emotion and action in the brain
Authors: Portugal Liana C L , Alves Rita C S , Fernandes-Junior Orlando , Sanchez Tiago A , Mocaiber Izabela , Volchan Eliane , Erthal Fátima , David Isabel A , Kim Jongwan , Oliveira Leticia , Padmala Srikanth , Chen Gang , Pessoa Luiz , Pereira Mirtes G
Published: October 2019

A growing literature supports the existence of interactions between emotion and action in the brain, and the central participation of the anterior midcingulate cortex (aMCC) in this regard. In the present functional magnetic resonance imaging study, we sought to investigate the role of self-relevance during such interactions by varying the context in which threating pictures were presented (with guns pointed towards or away from the observer). Participants performed a simple visual detection task following exposure to such stimuli. Except for voxelwise tests, we adopted a Bayesian analysis framework which evaluated evidence for the hypotheses of interest, given the data, in a continuous fashion. Behaviorally, our results demonstrated a valence by context interaction such that there was a tendency of speeding up responses to targets after viewing threat pictures directed towards the participant. In the brain, interaction patterns that paralleled those observed behaviorally were observed most notably in the middle temporal gyrus, supplementary motor area, precentral gyrus, and anterior insula. In these regions, activity was overall greater during threat conditions relative to neutral ones, and this effect was enhanced in the directed towards context. A valence by context interaction was observed in the aMCC too, where we also observed a correlation (across participants) of evoked responses and reaction time data. Taken together, our study revealed the context-sensitive engagement of motor-related areas during emotional perception, thus supporting the idea that emotion and action interact in important ways in the brain.
Synergistic population encoding and precise coordinated variability across interlaminar ensembles in the early visual system
Authors: Denman Daniel J , Reid R Clay
Published: October 2019

Sensory stimuli are represented by the joint activity of large populations of neurons across the mammalian cortex. Information in such responses is limited by trial-to-trial variability. Because that variability is not independent between neurons, it has the potential to improve or degrade the amount of sensory information in the population response. How visual information scales with population size remains an open empirical question. Here, we use Neuropixels to simultaneously record tens to hundreds of single neurons in primary visual cortex (V1) and lateral geniculate nucleus (LGN) of mice and estimate population information. We found a mix of synergistic and redundant coding: synergy predominated in small populations (2-12 cells) before giving way to redundancy. The shared variability of this coding regime included global shared spike count variability at longer timescales, layer specific shared spike count variability at finer timescales, and shared variability in spike timing (jitter) that linked ensembles that span layers. Such ensembles defined by their shared variability carry more information. Our results suggest fine time scale stimulus encoding may be distributed across physically overlapping but distinct ensembles in V1.
A Bayesian approach to inferring dispersal kernels with incomplete mark-recapture data
Authors: Terui Akira
Published: October 2019

Dispersal is a fundamental ecological process that links populations, communities and food webs in space. However, dispersal is tremendously difficult to study in the wild because we must track individuals dispersing in a landscape. One conventional method to measure animal dispersal is a mark-recapture technique. Despite its usefulness, this approach has been recurrently criticized because it is virtually impossible to survey all possible ranges of dispersal in nature. Here, I propose a novel Bayesian model to better estimate dispersal parameters from incomplete mark-recapture data. The dispersal-observation coupled model, DOCM, can extract information from both recaptured and unrecaptured individuals, providing less biased estimates of dispersal parameters. Simulations demonstrated the usefulness of DOCM under various sampling designs. I also suggest extensions of the DOCM to accommodate more realistic scenarios. Application of the DOCM may, therefore, provide valuable insights into how individuals disperse in the wild.
Developing a transcriptomic framework for testing testosterone-mediated handicap hypotheses
Authors: Newhouse Daniel J. , Vernasco Ben J.
Published: October 2019

Sexually selected traits are hypothesized to be honest signals of individual quality due to the costs associated with their maintenance, development, and/or production. Testosterone, a sex steroid associated with the development and/or production of sexually selected traits, has been proposed to enforce the honesty of sexually selected traits via its immunosuppressive effects (i.e., the Immunocompetence Handicap Hypothesis) and/or by influencing an individual’s exposure/susceptibility to oxidative stress (i.e., the Oxidation Handicap Hypothesis). Previous work testing these hypotheses has primarily focused on physiological measurements of immunity or oxidative stress, but little is known about the molecular pathways by which testosterone could influence immunity and/or oxidative stress pathways. To further understand the transcriptomic consequences of experimentally elevated testosterone in the context of handicap hypotheses, we used previously published RNA-seq data from studies that measured the transcriptome of individuals treated with either a testosterone-filled or an empty (i.e., control) implant. Two studies encompassing three species of bird and three tissue types fit our selection criteria and we reanalyzed the data using weighted gene co-expression network analysis. Our results show that testosterone-treated individuals exhibited signatures of immunosuppression and we provide some evidence to suggest that the transcriptomic signature of immunosuppression is evolutionarily conserved between the three species. While our results provide no evidence to suggest testosterone mediates handicaps via pathways associated with oxidative stress, they do support the hypothesis that testosterone enforces the honesty of sexually-selected traits by influencing an individual’s immunocompetence. Overall, this study develops a framework for testing testosterone-mediated handicap hypotheses and provides guidelines for future integrative and comparative studies focused on the proximate mechanisms mediating sexually selected traits.
Zebrafish cooperate while inspecting predators: experimental evidence for conditional approach
Authors: Pimentel Ana Flávia Nogueira , Lima-Maximino Monica Gomes , Soares Marta Candeias , Maximino Caio
Published: October 2019

Different fish species employ a conditional approach strategy during predator inspection; the risk of approaching a predator is distributed across all inspectors, but is not shared with the animals which keep its distance. Zebrafish, a highly social fish, is increasingly being used in behavioural neuroscience, but it is not known whether it displays conditional approach. In the predator inspection task, animals are observed in a tank with a refuge in one extremity, and an animated image of a predator in the other extremity, with a mirror positioned in parallel to the tank, simulating a perfectly reciprocating conspecific. In Experiment 1, animals spent more time in an inspection zone when the image was turned on, but also displayed more erratic swimming, suggesting cooperation under fear. In Experiment 2, animals spent more time inspecting predators when the mirror was parallel to the tank (“cooperating mirror”) than when the mirror was in an angle (“defecting mirror”), suggesting retaliatory behaviour; in both conditions, animals displayed more freezing and erratic swimming. In Experiment 3, no changes in behaviour were observed, regardless of mirror position, when the image was turned off, suggesting that the choice of specific zones in Experiment 2 was not due to shoaling tendencies. These results suggest that predator inspection is associated with conditional approach, while at the same time inducing fear-like behaviour in the animal.
Lesion of striatal patches disrupts habitual behaviors and increases behavioral variability
Authors: Nadel Jacob A. , Neidhart Maya , Pawelko Sean S. , Copes-Finke Della , Howard Christopher D.
Published: October 2019

Habits are automated behaviors that are insensitive to changes in behavioral outcomes. Habitual responding is thought to be mediated by striatum, with medial striatum guiding goal-directed action and lateral striatum promoting habits. However, interspersed throughout the striatum are neurochemically differing subcompartments known as patches, which are characterized by distinct molecular profiles relative to the surrounding matrix tissue. These structures have been thoroughly characterized neurochemically and anatomically, but little is known regarding their function. Patches have been shown to be selectively activated during inflexible motor stereotypies elicited by stimulants, suggesting that patches may subserve habitual behaviors. To explore this possibility, we utilized transgenic mice (Sepw1 NP67) expressing Cre recombinase in striatal patches to target these neurons for selective ablation with a virus driving Cre-dependent expression of caspase 3. Mice were then trained to press a lever for sucrose rewards on a variable interval schedule to elicit habitual responding. Mice were not impaired on the acquisition of this task, but lesioning striatal patches disrupted behavioral stability across training and lesioned mice utilized a more goal-directed behavioral strategy during training. Similarly, when mice were forced to omit responses to receive sucrose rewards, habitual responding was impaired in lesioned mice. To rule out effects of lesion on motor behaviors, mice were then tested for impairments in motor learning on a rotarod and locomotion in an open field. We found that patch lesions specifically impaired initial performance on the rotarod without modifying locomotor behaviors in open field. This work indicates that patches promote behavioral stability and habitual responding, adding to a growing literature implicating striatal patches in stimulus-response behaviors.
An Evaluation of the In Vitro Roles and Mechanisms of Silibinin in Reducing Pyrazinamide- and Isoniazid-Induced Hepatocellular Damage
Authors: Goh Zhang-He , Tee Jie Kai , Ho Han Kiat
Published: October 2019

Tuberculosis remains a significant infectious lung disease that affects millions of patients worldwide. Despite numerous existing drug regimens for tuberculosis, Drug-Induced Liver Injury is a major challenge that limits the effectiveness of these therapeutics. Two drugs that form the backbone of the commonly administered quadruple antitubercular regimen, i.e. pyrazinamide (PZA) and isoniazid (INH), are associated with such hepatotoxicity. The problem is compounded by the lack of safe and effective alternatives to the antitubercular regimen. Consequently, current research largely focuses on exploiting the hepatoprotective effect of nutraceutical compounds as complementary therapy. Silibinin, a herbal product widely believed to protect against various liver diseases, potentially provides a useful solution given its hepatoprotective mechanisms. In our study, we identified silibinin’s role in mitigating PZA- and INH-induced hepatotoxicity and elucidated a deeper mechanistic understanding of silibinin’s hepatoprotective ability. 25 μM silibinin preserved the viability of human foetal hepatocyte line LO2 when co-administered with 80 mM INH and decreased apoptosis induced by a combination of 40 mM INH and 10 mM PZA by reducing oxidative damage to mitochondria, proteins, and lipids. Taken together, this proof-of-concept forms the rational basis for the further investigation of silibinin’s hepatoprotective effect in subsequent preclinical studies and clinical trials.

Graphical Abstract
Rapid fabrication of collagen bundles mimicking tumor-associated collagen signatures
Authors: Gong Xiangyu , Kulwatno Jonathan , Mills K. L.
Published: October 2019

Stromal collagen surrounding a solid tumor tends to present as dense, thick bundles. The collagen bundles are remodeled during tumor progression: first tangential to the tumor boundary (indicating growth) and later perpendicular to the tumor boundary (indicating likely metastasis). Current reconstituted-collagenin vitrotumor models are unable to recapitulate thein vivostructural features of collagen bundling and alignment. Here, we present a rapid yet simple procedure to fabricate collagen bundles with an average thickness of 9 μm, compared to the reticular dense collagen nanofiber (∼900 nm-diameter, on average) prepared using common protocols. The versatility of the collagen bundles was demonstrated with their incorporation into twoin vitromodels where the thickness and alignment of the collagen bundles resembled the variousin vivoarrangements. First, collagen bundles aligned by a microfluidic device elicited cancer cell contact guidance and enhanced their directional migration. Second, the presence of the collagen bundles in a bio-inert agarose hydrogel was shown to provide a highway for cancer cell invasion. The unique structural features of the collagen bundles advance the physiological relevance ofin vitrocollagen-based tumor models for accurately capturing cancer cell-stroma interactions.