bluuebunny/crossref_metadata_2025 huggingface dataset:
Causes of Death of Residents in ACGME-Accredited Programs 2000 Through 2014: Implications for the Learning Environment
Authors: Yaghmour Nicholas A. , Brigham Timothy P. , Richter Thomas , Miller Rebecca S. , Philibert Ingrid , Baldwin DeWitt C. , Nasca Thomas J.
Published: May 2017

Purpose

To systematically study the number of U.S. resident deaths from all causes, including suicide.

Method

The more than 9,900 programs accredited by the Accreditation Council for Graduate Medical Education (ACGME) annually report the status of residents. The authors aggregated ACGME data on 381,614 residents in training during years 2000 through 2014. Names of residents reported as deceased were submitted to the National Death Index to learn causes of death. Person-year calculations were used to establish resident death rates and compare them with those in the general population.

Results

Between 2000 and 2014, 324 individuals (220 men, 104 women) died while in residency. The leading cause of death was neoplastic disease, followed by suicide, accidents, and other diseases. For male residents the leading cause was suicide, and for female residents, malignancies. Resident death rates were lower than in the age- and gender-matched general population. Temporal patterns showed higher rates of death early in residency. Deaths by suicide were higher early in training, and during the first and third quarters of the academic year. There was no upward or downward trend in resident deaths over the 15 years of this study.

Conclusions

Neoplastic disease and suicide were the leading causes of death in residents. Data for death by suicide suggest added risk early in residency and during certain months of the academic year. Providing trainees with a supportive environment and with medical and mental health services is integral to reducing preventable deaths and fostering a healthy physician workforce.
Ondansetron Does Not Reduce Withdrawal in Patients With Physical Dependence on Chronic Opioid Therapy
Authors: Chu Larry F. , Sun John , Clemenson Anna , Erlendson Matthew J. , Rico Tom , Cornell Erika , Obasi Hannah , Sayyid Zahra N. , Encisco Ellen M. , Yu Jeff , Gamble Jamison G. , Carroll Ian , Clark J. David
Published: May 2017

Objectives:

Individuals taking opioids for an extended period of time may become physically dependent, and will therefore experience opioid withdrawal should they stop taking the medication. Previous work in animal and human models has shown that the serotonin (5-HT3) receptor may be implicated in opioid withdrawal. In this study, we investigated if ondansetron, a 5-HT3-receptor antagonist, could reduce the symptoms of opioid withdrawal after chronic opioid exposure in humans.

Methods:

In this double-blinded, randomized, crossover study, 33 chronic back pain patients (N = 33) were titrated onto sustained-release oral morphine for 30 days. After titration, participants attended 2 study sessions, 1 week apart, in which opioid withdrawal was induced with intravenous naloxone, with or without 8 mg intravenous ondansetron pretreatment. Opioid withdrawal symptoms were assessed by a blinded research assistant (objective opioid withdrawal score [OOWS]) and by the research participant (subjective opioid withdrawal score [SOWS]).

Results:

Clinically significant signs of withdrawal were observed during both the ondansetron (ΔOOWS = 3.58 ± 2.22, P < 0.0001; ΔSOWS = 12.48 ± 11.18, P < 0.0001) and placebo sessions (ΔOOWS = 3.55 ± 2.39, P < 0.0001; ΔSOWS = 12.21 ± 10.72, P < 0.0001), but no significant differences were seen between the treatment sessions in either the OOWS or SOWS scores.

Conclusion:

We hypothesized that ondansetron would reduce opioid withdrawal symptoms in human subjects, but found no difference in withdrawal severity between ondansetron and placebo sessions. These findings suggest that more investigation may be necessary to determine if 5-HT3-receptor antagonists are suitable treatment options for opioid withdrawal.
Phrenic Nerve Palsy and Regional Anesthesia for Shoulder Surgery
Authors: El-Boghdadly Kariem , Chin Ki Jinn , Chan Vincent W. S.
Published: May 2017

Regional anesthesia has an established role in providing perioperative analgesia for shoulder surgery. However, phrenic nerve palsy is a significant complication that potentially limits the use of regional anesthesia, particularly in high-risk patients. The authors describe the anatomical, physiologic, and clinical principles relevant to phrenic nerve palsy in this context. They also present a comprehensive review of the strategies for reducing phrenic nerve palsy and its clinical impact while ensuring adequate analgesia for shoulder surgery. The most important of these include limiting local anesthetic dose and injection volume and performing the injection further away from the C5–C6 nerve roots. Targeting peripheral nerves supplying the shoulder, such as the suprascapular and axillary nerves, may be an effective alternative to brachial plexus blockade in selected patients. The optimal regional anesthetic approach in shoulder surgery should be tailored to individual patients based on comorbidities, type of surgery, and the principles described in this article.
Associations Between Parental Factors and Child Diabetes-Management–Related Behaviors
Authors: Lohan Aditi , Morawska Alina , Mitchell Amy
Published: May 2017

Objective:

Adherence to diabetes-management regimens in children requires teamwork and consistency from both parents and children. This study investigated a mediational model developed to understand the relationship between different modifiable parent factors influencing child diabetes-related behaviors.

Methods:

We recruited 186 parents of children aged 2 to 10 years with Type 1 diabetes to complete self-report questionnaires on child diabetes behavior, parental self-efficacy with managing the child's behavior, parent diabetes self-efficacy, parent adjustment, condition management effort, parent perception of their diabetes knowledge, and parenting behavior. We used structural equation modeling in AMOS to test our hypothesized model of interrelationships between variables associated with child diabetes behavior.

Results:

The hypothesized model provided good fit to the data. We found that parent perception of low levels of diabetes knowledge and higher levels of condition management effort, and parent adjustment difficulties were associated with lower parental self-efficacy with diabetes management. This was further linked with lower levels of parental self-efficacy with managing their child's diabetes behavior, and consequently, higher extent of child diabetes behavior problems. Contrary to our expectations, we did not find a significant effect of parenting behavior on child diabetes behavior problems, either directly or indirectly via parent self-efficacy for managing child's behavior.

Conclusion:

Our findings shed light on the mechanisms through which different parenting factors interact and are associated with diabetes behavior in children. These factors can be targeted through parenting interventions to improve child's cooperation with diabetes-management tasks and reduce barriers to effective management.
Challenges for Detecting Valproic Acid in a Nontargeted Urine Drug Screening Method
Authors: Pope Jeffrey D. , Black Marion J. , Drummer Olaf H. , Schneider Hans G.
Published: May 2017

Background:

Valproic acid (VPA) is a widely prescribed medicine, and acute toxicity is possible. As such, it should be included in any nontargeted urine drug screening method. In many published liquid chromatography–electrospray ionization–mass spectrometry (LC–ESI–MS/MS) methods, VPA is usually measured using a pseudo-multiple reaction monitoring (MRM) transition. We investigate a simple ultra-high-performance liquid chromatography–quadrupole time-of-flight (QTof) approach to detect the presence of VPA with more confidence.

Methods:

Three commercially sourced VPA metabolites were characterized and added to a nontargeted high-resolution MS urine drug screening method. All analyses were performed on a Waters Xevo G2-XS LC-QTof in negative electrospray ionization mode. The mass detector was operated in MSE mode, and data were processed with UNIFI software. Sixty-eight patient urine samples, which were previously identified by a well-established gas chromatography–MS method as containing VPA, were analyzed on the Waters Xevo G2-XS LC-QTof, to validate this approach.

Results:

VPA metabolite standards were characterized, and their detection data were added to the broad drug screening library. VPA metabolites were readily detectable in the urine of patients taking VPA.

Conclusions:

The inclusion of characterized VPA metabolites provides a simple and reliable method enabling the detection of VPA in nontargeted urine drug screening.
The role of simulation and warm-up in minimally invasive gynecologic surgery
Authors: Moulder Janelle K. , Louie Michelle , Toubia Tarek , Schiff Lauren D. , Siedhoff Matthew T.
Published: May 2017

Purpose of review

The purpose of the review is to update the reader on the current literature and recent studies evaluating the role of simulation and warm-up as part of surgical education and training, and maintenance of surgical skills.

Recent findings

Laparoscopic and hysteroscopic simulation may improve psychomotor skills, particularly for early-stage learners. However, data are mixed as to whether simulation education is directly transferable to surgical skill. Data are insufficient to determine if simulation can improve clinical outcomes. Similarly, performance of surgical warm-up exercises can improve performance of novice and expert surgeons in a simulated environment, but the extent to which this is transferable to intraoperative performance is unknown. Surgical coaching, however, can facilitate improvements in performance that are directly reflected in operative outcomes.

Simulation-based curricula may be a useful adjunct to residency training, whereas warm-up and surgical coaching may allow for maintenance of skill throughout a surgeon's career. These experiences may represent a strategy for maintaining quality and value in a lower volume surgical setting.
Decreased Visual Acuity by an Irregular Corneal Posterior Surface After Repeat Descemet Stripping Automated Endothelial Keratoplasty
Authors: Yazu Hiroyuki , Yamaguchi Takefumi , Dogru Murat , Satake Yoshiyuki , Tsubota Kazuo , Shimazaki Jun
Published: May 2017

Purpose:

To investigate the impact of higher-order aberrations (HOAs) on visual acuity after repeat Descemet stripping automated endothelial keratoplasty (DSAEK) in the same eyes.

Methods:

This retrospective comparative case series includes 23 patients who underwent DSAEK twice in the same eyes (46 DSAEK in total). We evaluated the HOAs of the anterior and posterior corneal surfaces, and total cornea using the Fourier analysis data from anterior segment optical coherence tomography. Eyes were divided into one of the following groups, based on the improvement and decline in the best-corrected visual acuity (BCVA) after repeat DSAEK; group A: 12 eyes with an improvement ≥ 2 lines, group B: 12 eyes with a decline ≤ 2 lines, and group C: 11 eyes with no change or change within 1 line.

Results:

The HOAs of the posterior surface in group B were significantly greater than those of group A (P=0.028), whereas there were no significant differences in the anterior surface and total corneal HOAs between groups A and B (P=0.12 and 0.08). There were no significant differences in the anterior and posterior surface as well as total cornea HOAs between initial DSAEK and repeat DSAEK in group C (P=0.87, 0.65, and 0.42). The postoperative BCVA had a significant correlation with the HOAs of the anterior and posterior surfaces as well as the total cornea (R=0.40, 0.46, and 0.53; P=0.01, 0.002, and 0.001).

Conclusions:

Posterior corneal HOAs can have a negative influence on the visual acuity after endothelial keratoplasty.
Sentinel Lymph Node Technique in Endometrial Cancer
Authors: Staley Allison , Sullivan Stephanie A. , Rossi Emma C.
Published: May 2017

Importance

Endometrial cancer (EMCA) is the most common gynecologic malignancy, with an estimated 54,000 new cases and 10,000 deaths in the United States in 2015. Lymph node metastasis is the most significant prognostic factor in EMCA. Sentinel lymph node (SLN) mapping has become a well-accepted procedure in surgical oncology and may strike a balance between the risks and benefits of lymphadenectomy.

Objective

The aim of this study was to review the current literature regarding the history, techniques, and clinical application of SLN mapping in EMCA.

Evidence Acquisition

Evidence was obtained through systematic literature review through PubMed and ClinicalTrials.gov.

Conclusions

Sentinel lymph node biopsy for EMCA is an accepted approach to the staging of this cancer; however, a consensus approach to the SLN biopsy technique and pathologic assessment is needed. Surgeons newly adopting the technique should proceed with caution and care to monitor outcomes.

Target Audience

Obstetricians and gynecologists, family physicians

Learning Objectives

After completing this activity, the learner should be better able to describe the importance of lymph node metastasis in EMCA prognosis, recognize the various techniques for SLN biopsy, describe the history of the SLN, and recognize the potential clinical application for SLN biopsy in the treatment of EMCA.
Gonadotropin-Releasing Hormone–Agonist Triggering and a Freeze-All Approach: The Final Step in Eliminating Ovarian Hyperstimulation Syndrome?
Authors: Davenport Marcus J. , Vollenhoven Beverley , Talmor Alon J.
Published: May 2017

Importance

In vitro fertilization (IVF) has evolved dramatically in recent decades; however, clinical practices have been slow to adopt these advancements, particularly regarding final oocyte maturation and the timing of embryo transfer. Concerns still exist over the ability of gonadotropin-releasing hormone (GnRH) agonists and elective embryo cryopreservation to reduce the risk of ovarian hyperstimulation syndrome (OHSS) without compromising pregnancy outcomes.

Objective

This review investigates IVF outcomes associated with GnRH-agonist triggering and elective embryo cryopreservation. The safety and efficacy of GnRH-agonist triggering are compared with conventional human chorionic gonadotropin triggering, and frozen embryo transfers are weighed against fresh transfers.

Evidence Acquisition

A literature search was conducted using OVID (MEDLINE) and PubMed databases. The search strategy included keywords such as “ovarian hyperstimulation syndrome or OHSS,” “GnRH-agonist triggering,” “cryopreservation or freeze-all,” and “IVF outcomes.” A total of 214 articles were considered for review.

Results

Gonadotropin-releasing hormone agonist triggering reduces OHSS incidence without compromising oocyte retrieval and fertilization rates in donor and autologous cycles. However, GnRH-agonist triggering causes a luteal phase deficiency in autologous cycles, deleteriously compromising pregnancy rates. Elective embryo cryopreservation overcomes this deficiency, reducing the risk of OHSS and may improve neonatal and obstetric outcomes.

Conclusions

Gonadotropin-releasing hormone agonist triggering should be considered in all donor cycles. It should also be selectively considered in autologous cycles in combination with elective cryopreservation of all viable embryos.

Target Audience

Obstetricians and gynecologists, family physicians.

Learning Objectives

After completing this activity, the learner should be better able to (1) outline the pathogenesis and prevention of OHSS; (2) select patients who are at high risk of OHSS; (3) compare therapeutic options for oocyte triggering and the outcomes associated with fresh and frozen transfers; and (4) explain and rationalize the routine use of GnRH-agonist triggering and elective embryo cryopreservation in everyday practice.
Evaluation of Microscopic Hematuria and Risk of Urologic Cancer in Female Patients
Authors: Lippmann Quinn K. , Slezak Jeff M. , Menefee Shawn A. , Ng Casey K. , Whitcomb Emily L. , Loo Ronald K.
Published: May 2017

(Abstracted from Am J Obstet Gynecol 2017;216:146.e1–146.e7)

Microscopic hematuria (MH) is common in men and women, but its prevalence is higher in women probably because of benign conditions. Although urologic cancer has a lower prevalence in women than men, there is no difference in the recommended evaluation for women and men with MH.
Repealing the ACA Without a Replacement—The Risks to American Health Care
Authors: Obama Barack H.
Published: May 2017

(Abstracted from N Engl J Med 2017;376:297–299)

In this article, former American president Barack Obama outlines how and why repealing the Affordable Care Act (ACA) without a proper substitute in place will harm US health care. He reviews the progress made as a result of the ACA while also acknowledging the work still to be done.
Effects of local and spinal administrations of mu-opioids on postoperative pain in aged vs adult mice
Authors: Mecklenburg Jennifer , Patil Mayur J. , Koek Wouter , Akopian Armen N.
Published: May 2017

Introduction:

Suboptimal management of postoperative pain leads to increased risk of chronic opioid therapy, especially in elderly patients.

Objectives:

Although this age-dependent phenomenon has been observed clinically, basic mechanisms including baseline nociception, postoperative hypersensitivity, and mu-opioid efficiency in aged animals have never been evaluated.

Methods:

We tested these criteria using incision model on adult (3–6 months) and aged (24 months) mice to assess translatability of postoperative animal studies to clinical observations.

Results:

Thermal and mechanical testing revealed lower baseline nociception in aged vs adult mice, while behavioral assays after hind paw plantar incision showed similar hypersensitivity levels for both age groups. Efficiency of local and spinal mu-opioid injections on postoperative pain was assessed next. DAMGO, a pure mu-opioid, was effective in reducing postoperative hypersensitivity in aged and adult mice, although adult mice displayed increased sensitivity to higher doses (50 μg local; 1–15 μg spinal). Buprenorphine, a mixed mu-opioid agonist, produced dose-dependent antihypersensitivity with adult mice more sensitive to lower doses (0.1 μg local; 0.02 μg spinal), and aged mice more sensitive to higher doses (1, 10 μg local; 0.1, 1 μg spinal). Finally, exploratory locomotor activity was used to evaluate the suppression of incision-induced spontaneous pain by DAMGO. Spinal and systemic (intraperitoneal) DAMGO inhibited ongoing pain more in adults compared with aged mice.

Conclusion:

As in humans, baseline nociception was lower in aged vs adult mice, while postoperative hypersensitivity magnitudes were comparable between groups. Unlike in humans, adult mice were more sensitive to mu-opioids, although higher doses of mixed mu-opioids were more effective for postoperative antihypersensitivity in aged mice.
Δ9-Tetrahydrocannabinol Suppresses Secretion of IFNα by Plasmacytoid Dendritic Cells From Healthy and HIV-Infected Individuals
Authors: Henriquez Joseph E. , Rizzo Michael D. , Schulz Matthias A. , Crawford Robert B. , Gulick Peter , Kaminski Norbert E.
Published: May 2017

Plasmacytoid dendritic cells (pDCs) play a crucial role in host antiviral immune response through secretion of type I interferon. Interferon alpha (IFNα), a type I IFN, is critical for mounting the initial response to viral pathogens. A consequence of Human Immunodeficiency Virus-1 (HIV) infection is a decrease in both pDC number and function, but prolonged pDC activity has been linked with progression from HIV infection to the development of AIDS. Patients with HIV in the United States routinely use cannabinoid-based therapies to combat the side effects of HIV infection and antiretroviral therapy. However, cannabinoids, including Δ9-tetrahydrocannabinol (THC), are well-characterized immunosuppressants. Here, we report that THC suppressed secretion of IFNα by pDC from both healthy and HIV+ donors through a mechanism involving impaired phosphorylation of interferon regulatory factor 7. These results suggest that THC can suppress pDC function during the early host antiviral response by dampening pDC activation.
The Effectiveness and Feasibility of Endoscopic Ultrasound-guided Transgastric Drainage of Postoperative Fluid Collections Early After Pancreatic Surgery
Authors: Futagawa Yasuro , Imazu Hiroo , Mori Naoki , Kanazawa Keisuke , Chiba Masafumi , Furukawa Kenei , Sakamoto Taro , Shiba Hiroaki , Yanaga Katsuhiko
Published: May 2017

Purposes:

To assess the feasibility and usefulness of endoscopic ultrasound-guided transgastric drainage (EUS-GD) in patients who required early postoperative drainage of peripancreatic fluid collection or postoperative pancreatic fistulas after pancreatic surgery.

Patients and Methods:

Between May 2012 and January 2016, 33 patients who developed peripancreatic fluid collection or postoperative pancreatic fistulas after pancreatic resection underwent EUS-GD or percutaneous drainage (PTD). Outcomes were compared retrospectively.

Results:

The drainage procedures were performed on postoperative day 4 to 71 (median, 12) in the EUS-GD group, and 7 to 35 (median, 14) in the PTD group. Technical and clinical success rates reached 92% (11/12) in the EUS-GD group, and 100% (21/21) in the PTD group with no complications or mortality. The duration of hospital stay after drainage was 10 to 44 (median, 15) days for EUS-GD, compared with 10 to 39 (median, 21) days for PTD.

Conclusions:

EUS-GD is a safe and useful method for early drainage, which could be a good alternative to PTD.
Laparoscopic Management of Hepatocellular Carcinoma: A Critical Reappraisal
Authors: Fuks David , Aldrighetti Luca , Jiao Long R. , Wakabayashi Go , Limongelli Paolo
Published: May 2017

Following the introduction of the first laparoscopic liver resection, after ∼25 years, a critical reappraisal seems to be warranted. Liver resection represents the first choice for curing early hepatocellular carcinoma (HCC) allowing a curative chance also in selected patients with intermediate stage tumors. The criteria for liver resectability by laparoscopy remains the same for open surgery, which is oncological criteria (absence of extrahepatic tumor location; completely resectable R0 resection), anatomic (resectability of involved segment with its own blood surely and biliary drainage; absence of vascular invasion of portal or hepatic veins) and technical (possibility to leave in place a residual volume ≥40%). Anatomic resections being more challenging than wedged resections, were initially performed mainly for lesions located in the left liver (segments 2, 3, and 4) and segments 5 and 6 of the right liver (anterior and lateral hepatic segments). Left lateral segmentectomy seemed most suited for laparoscopic resection because of the thinness of the liver, the possibility of resection without hilar dissection, ease of stapling the left hepatic vein and portal pedicles of segment II and III by mechanical stapling. Conversely, right hepatectomy seemed most difficult and technically challenging to perform. The analysis of literature confirms that minor liver resections for HCC can be safely conducted also in cirrhotic patients and that laparoscopy, when feasible, should be the approach of first choice. As mentioned, there have been several studies that compared the long-term outcomes of laparoscopic hepatectomy (LH) versus open hepatectomy for HCC, even in cirrhotic patients, showing that laparoscopy does not seem to have any impact on the risk of postoperative HCC recurrence. However, further studies seem to be required, especially for long-term oncological results and for major hepatectomy, before LH become a common alternative to open liver surgery. The practice of performing LH (major) is challenging, due to the significant complexity of these interventions.
A Systematic Review and Meta-Analysis of Laparoscopic and Open Distal Pancreatectomy of Nonductal Adenocarcinomatous Pancreatic Tumor (NDACPT) in the Pancreatic Body and Tail
Authors: Yi Xiaojiang , Chen Sile , Wang Wei , Zou Liaonan , Diao Dechang , Zheng Yansheng , He Yaobin , Li Hongming , Luo Lijie , Xiong Wenjun , Wan Jin
Published: May 2017

Background:

Currently, laparoscopic distal pancreatectomy is regarded as a safe and effective surgical approach for lesions in the body and tail of the pancreas. This review examined the evidence from published data of comparative studies of laparoscopic versus open distal pancreatectomy of nonductal adenocarcinomatous pancreatic tumor in pancreatic body and tail.

Methods:

A systematic review of the studies comparing laparoscopic and open distal pancreatectomy was conducted. Comparative studies published between January 1996 and June 2016 were included. Studies were selected on the basis of specific inclusion and exclusion criteria. These 2 techniques were compared regarding several outcomes of interest, which were divided into preoperative, operative, postoperative, and pathologic characteristics, postoperative biomarker, and hospital stay cost. Sensitivity and subgroup analysis partially confirmed the robustness of these data.

Results:

Ten comparative case-control studies involving 712 patients (53.7% laparoscopic and 46.3% open), who underwent a distal pancreatectomy were included. The results favored laparoscopy with regard to intraoperative blood loss (P=0.0001), the rate of blood transfusion (P=0.02), total hospital stay (P=0.004), postoperative hospital stay (P<0.0001), overall morbidity (P=0.0002), the rate of wound infection (P=0.05), time to initial feeds (P<0.0001), first flatus time (P=0.008), duration of pain-killer intake (P=0.0003), and C-reactive protein on postoperative day 1 (P=<0.0001). In the subgroup analysis, excluding western country studies, operation time changed to have a statistically significant difference between these 2 groups (P=0.02).

Conclusions:

Laparoscopic resection results in improved operative and postoperative outcomes compared with open surgery according to the results of the present meta-analysis. It may be a safe and feasible option for nonductal adenocarcinomatous pancreatic tumor patients in pancreatic body and tail. However, randomized controlled trials should be undertaken to confirm the relevance of these findings.
The unusual tracheal system within the wing membrane of a dragonfly
Authors: Guillermo-Ferreira Rhainer , Appel Esther , Urban Paulina , Bispo Pitágoras C. , Gorb Stanislav N.
Published: May 2017

Some consider that the first winged insects had living tissue inside the wing membrane, resembling larval gills or developing wing pads. However, throughout the developmental process of the wing membrane of modern insects, cells and tracheoles in the lumen between dorsal and ventral cuticle disappear and both cuticles become fused. This process results in the rather thin rigid stable structure of the membrane. The herewith described remarkable case of the dragonflyZenithoptera laneishows that in some highly specialized wings, the membrane can still be supplemented by tracheae. Such a characteristic of the wing membrane presumably represents a strong specialization for the synthesis of melanin-filled nanolayers of the cuticle, nanospheres inside the wing membrane and complex arrangement of wax crystals on the membrane surface, all responsible for unique structural coloration.
Post-fire recovery of torpor and activity patterns of a small mammal
Authors: Stawski Clare , Hume Taylor , Körtner Gerhard , Currie Shannon E. , Nowack Julia , Geiser Fritz
Published: May 2017

To cope with the post-fire challenges of decreased availability of food and shelter, brown antechinus (
Antechinus stuartii
), a small marsupial mammal, increase the use of energy-conserving torpor and reduce activity. However, it is not known how long it takes for animals to resume pre-fire torpor and activity patterns during the recovery of burnt habitat. Therefore, we tested the hypothesis that antechinus will adjust torpor use and activity after a fire depending on vegetation recovery. We simultaneously quantified torpor and activity patterns for female antechinus from three adjacent areas: (i) the area of a management burn 1 year post-fire, (ii) an area that was burned 2 years prior, and (iii) a control area. In comparison to shortly after the management burn, antechinus in all three groups displayed less frequent and less pronounced torpor while being more active. We provide the first evidence that only 1 year post-fire antechinus resume pre-fire torpor and activity patterns, probably in response to the return of herbaceous ground cover and foraging opportunities.
Mechanotransmission in endothelial cells subjected to oscillatory and multi-directional shear flow
Authors: Dabagh Mahsa , Jalali Payman , Butler Peter J. , Randles Amanda , Tarbell John M.
Published: May 2017

Local haemodynamics are linked to the non-uniform distribution of atherosclerosic lesions in arteries. Low and oscillatory (reversing in the axial flow direction) wall shear stress (WSS) induce inflammatory responses in endothelial cells (ECs) mediating disease localization. The objective of this study is to investigate computationally how the flow direction (reflected in WSS variation on the EC surface over time) influences the forces experienced by structural components of ECs that are believed to play important roles in mechanotransduction. A three-dimensional, multi-scale, multi-component, viscoelastic model of focally adhered ECs is developed, in which oscillatory WSS (reversing or non-reversing) parallel to the principal flow direction, or multi-directional oscillatory WSS with reversing axial and transverse components are applied over the EC surface. The computational model includes the glycocalyx layer, actin cortical layer, nucleus, cytoskeleton, focal adhesions (FAs), stress fibres and adherens junctions (ADJs). We show the distinct effects of atherogenic flow profiles (reversing unidirectional flow and reversing multi-directional flow) on subcellular structures relative to non-atherogenic flow (non-reversing flow). Reversing flow lowers stresses and strains due to viscoelastic effects, and multi-directional flow alters stress on the ADJs perpendicular to the axial flow direction. The simulations predict forces on integrins, ADJ filaments and other substructures in the range that activate mechanotransduction.
Putting the waste out: a proposed mechanism for transmission of the mycoparasite
Escovopsis
between leafcutter ant colonies
Authors: Augustin Juliana O. , Simões Talitta G. , Dijksterhuis Jan , Elliot Simon L. , Evans Harry C.
Published: May 2017

The attine ant system is a remarkable example of symbiosis. An antagonistic partner within this system is the fungal parasite
Escovopsis
, a genus specific to the fungal gardens of the Attini.
Escovopsis
parasitizes the
Leucoagaricus
symbiont that leaf-cutting ants (
Acromyrmex
,
Atta
) have been farming over the past 8–12 Myr. However, it has been a puzzle how
Escovopsis
reaches its host. During a seasonal survey of nests of
Acromyrmex subterraneus subterraneus
in Atlantic rainforest in Brazil,
Escovopsis
was detected in all the sampled fungal garden waste tips or middens (
n
 = 111). Middens were built strategically; always below the nest entrances. Here, we report the first evidence of a putative mechanism for horizontal transmission of
Escovopsis
between attine colonies. It is posited that leaf-cutting ants pick up the spores from soil and litter during foraging and vector the mycoparasite between attine colonies. Field and laboratory experiments, using
At. laevigata
and
Ac. subterraneus subterraneus
, confirm that
Escovopsis
spores are phoretic, and have an inbuilt dormancy, broken by the presence of their
Leucoagaricus
host. However, in the coevolutionary arms race,
Atta
ants may lose out—despite most species in the genus investing in a more advanced waste disposal system—due to the insanitary habits of their
Acromyrmex
neighbours.
Development of cyclic shedding teeth from semi-shedding teeth: the inner dental arcade of the stem osteichthyan
Lophosteus
Authors: Chen Donglei , Blom Henning , Sanchez Sophie , Tafforeau Paul , Märss Tiiu , Ahlberg Per E.
Published: May 2017

The numerous cushion-shaped tooth-bearing plates attributed to the stem group osteichthyan
Lophosteus superbus
, which are argued here to represent an early form of the osteichthyan inner dental arcade, display a previously unknown and presumably primitive mode of tooth shedding by basal hard tissue resorption. They carry regularly spaced, recumbent, gently recurved teeth arranged in transverse tooth files that diverge towards the lingual margin of the cushion. Three-dimensional reconstruction from propagation phase-contrast synchrotron microtomography (PPC-SRµCT) reveals remnants of the first-generation teeth embedded in the basal plate, a feature never previously observed in any taxon. These teeth were shed by semi-basal resorption with the periphery of their bases retained as dentine rings. The rings are highly overlapped, which evidences tooth shedding prior to adding the next first-generation tooth at the growing edge of the plate. The first generation of teeth is thus diachronous. Successor teeth at the same sites underwent cyclical replacing and shedding through basal resorption, producing stacks of buried resorption surfaces separated by bone of attachment. The number and spatial arrangement of resorption surfaces elucidates that basal resorption of replacement teeth had taken place at the older tooth sites before the addition of the youngest first-generation teeth at the lingual margin. Thus, the replacement tooth buds cannot have been generated by a single permanent dental lamina at the lingual edge of the tooth cushion, but must have arisen either from successional dental laminae associated with the individual predecessor teeth, or directly from the dental epithelium of these teeth. The virtual histological dissection of these Late Silurian microfossils broadens our understanding of the development of the gnathostome dental systems and the acquisition of the osteichthyan-type of tooth replacement.
Big cityBombus: using natural history and land-use history to find significant environmental drivers in bumble-bee declines in urban development
Authors: Glaum Paul , Simao Maria-Carolina , Vaidya Chatura , Fitch Gordon , Iulinao Benjamin
Published: May 2017

Native bee populations are critical sources of pollination. Unfortunately, native bees are declining in abundance and diversity. Much of this decline comes from human land-use change. While the effects of large-scale agriculture on native bees are relatively well understood, the effects of urban development are less clear. Understanding urbanity's effect on native bees requires consideration of specific characteristics of both particular bee species and their urban landscape. We surveyed bumble-bee (Bombusspp.) abundance and diversity in gardens across multiple urban centres in southeastern Michigan. There are significant declines inBombusabundance and diversity associated with urban development when measured on scales in-line withBombusflight ability. These declines are entirely driven by declines in females; males showed no response to urbanization. We hypothesize that this is owing to differing foraging strategies between the sexes, and it suggests reducedBombuscolony density in more urban areas. While urbanity reducedBombusprevalence, results in Detroit imply that ‘shrinking cities’ potentially offer unique urban paradigms that must be considered when studying wild bee ecology. Results show previously unidentified differences in the effects of urbanity on female and male bumble-bee populations and suggest that urban landscapes can be managed to support native bee conservation.
Convective instabilities of Maxwell–Cattaneo fluids
Authors: Eltayeb I. A.
Published: May 2017

Motivated by the need to understand better the dynamics of non-Fourier fluids, we examine the linear and weakly nonlinear stabilities of a horizontal layer of fluid obeying the Maxwell–Cattaneo relationship of heat flux and temperature using three different forms of the time derivative of the heat flux. Linear stability mode regime diagrams in the parameter plane have been established and used to summarize the linear instabilities. The energy balance of the system is used to identify the mechanism by which the Maxwell–Cattaneo effect (i) introduces overstability, (ii) leads to preferred stationary modes with the critical Rayleigh and wavelengths either both increasing or both decreasing, (iii) gives rise to instabilities in a layer heated from above, and (iv) enhances heat transfer. A formal weakly nonlinear analysis leads to evolution equations for the amplitudes of linear instability modes. It is shown that the amplitude of the stationary mode obeys an equation of the Landau–Stuart type. The two equally excitable overstable modes obey two equations of the same type coupled by an interaction term. The evolution of the different amplitudes leads to supercritical stability, supercritical instability or subcritical instability depending on the model and parameter values. The results are presented in regime diagrams.
Post-transcriptional control of EMT is coordinated through combinatorial targeting by multiple microRNAs
Authors: Cursons Joseph , Pillman Katherine A , Scheer Kaitlin , Gregory Philip A , Foroutan Momeneh , Zadeh Soroor Hediyeh , Toubia John , Crampin Edmund J , Goodall Gregory J , Bracken Cameron P , Davis Melissa J
Published: May 2017

Epithelial-mesenchymal transition (EMT) is a process whereby cells undergo reversible phenotypic change, losing epithelial characteristics and acquiring mesenchymal attributes. While EMT underlies normal, physiological programs in embryonic tissue development and adult wound healing, it also contributes to cancer progression by facilitating metastasis and altering drug sensitivity. Using a cell model of EMT (human mammary epithelial (HMLE) cells), we show that miRNAs act as an additional regulatory layer over and above the activity of the transcription factors with which they are closely associated. In this context, miRNAs serve to both enhance expression changes for genes with EMT function, whilst simultaneously reducing transcriptional noise in non-EMT genes. We find that members of the polycistronic miR-200c~141 and miR-183~182 clusters (which are decreased during HMLE cell EMT and are associated with epithelial gene expression in breast cancer patients) co-regulate common targets and pathways to enforce an epithelial phenotype. We demonstrate their combinatorial effects are apparent much closer to endogenous expression levels (and orders of magnitude lower than used in most studies). Importantly, the low levels of combinatorial miRNAs that are required to exert biological function ameliorate the “off-target” effects on gene expression that are a characteristic of supra-physiologic miRNA manipulation. We argue that high levels of over-expression characteristic of many miRNA functional studies have led to an over-estimation of the effect of many miRNAs in EMT regulation, with over 130 individual miRNAs directly implicated as drivers of EMT. We propose that the functional effects of co-regulated miRNAs that we demonstrate here more-accurately reflects the endogenous post-transcriptional regulation of pathways, networks and processes, and illustrates that the post-transcriptional miRNA regulatory network is fundamentally cooperative.
I like coffee with cream anddog?Change in an implicit probabilistic representation captures meaning processing in the brain
Authors: Rabovsky Milena , Hansen Steven S. , McClelland James L.
Published: May 2017

The N400 component of the event-related brain potential has aroused much interest because it is thought to provide an online measure of meaning processing in the brain. Yet, the underlying process remains incompletely understood and actively debated. Here, we present a computationally explicit account of this process and the emerging representation of sentence meaning. We simulate N400 amplitudes as the change induced by an incoming stimulus in an implicit and probabilistic representation of meaning captured by the hidden unit activation pattern in a neural network model of sentence comprehension, and we propose that the process underlying the N400 also drives implicit learning in the network. The model provides a unified account of 16 distinct findings from the N400 literature and connects human language processing with successful deep learning approaches to language processing.
Geometrical confinement guides Brachyury self-patterning in embryonic stem cells
Authors: Guillaume Blin , Picart Catherine , Thery Manuel , Puceat Michel
Published: May 2017

During embryogenesis, signaling molecules initiate cell diversification, sometimes via stochastic processes, other times via the formation of long range gradients of activity which pattern entire fields of cells. Such mechanisms are not insensitive to noise (Lander, 2011), yet embryogenesis is a remarkably robust process suggesting that multiple layers of regulations secure patterning during development. In the present study, we present a proof of concept according to which an asymmetric pattern of gene expression obtained from a spatially disorganised population of cells can be guided by the geometry of the environment in a reproducible and robust manner. We used ESC as a model system whithin which multiple developmental cell states coexist (MacArthur and Lemischka, 2013; Smith, 2017; Torres-Padilla and Chambers, 2014). We first present evidence that a reciprocal regulation of genes involved in the establishment of antero-posterior polarity during peri-implantation stages of mouse development is spontaneously occuring within ESC. We then show that a population of cells with primitive streak characteristics localise in regions of high curvature and low cell density. Finally, we show that this patterning did not depend on self-organised gradients of morphogen activity but instead could be attributed to positional rearrangements. Our findings unveil a novel role for tissue geometry in guiding the self-patterning of primitive streak cells and provide a framework to further refine our understanding of symmetry breaking events occuring in ESC aggregates. Finally, this work demonstrates that the self-patterning of a specific population of ESC, Brachyury positive cells in this case, can be directed by providing engineered external geometrical cues.
Dynamic allocation of orthogonal ribosomes facilitates uncoupling of co-expressed genes
Authors: Darlington Alexander P.S. , Kim Juhyun , Jiménez José I. , Bates Declan G.
Published: May 2017

Introduction of synthetic circuits into host microbes creates competition between circuit and host genes for shared cellular resources, such as RNA polymerases and ribosomes. This can lead to the emergence of unwanted coupling between the expression of different genes, complicating circuit design and potentially leading to circuit failure. Here we demonstrate the ability of orthogonal ribosomes to alleviate the effects of this resource competition. We partition the ribosome pool by expressing an engineered 16S RNA with altered specificity, and use this division of specificity to build simple resource allocators which reduce the level of ribosome-mediated gene coupling. We then design and implement a dynamic resource allocation controller, which acts to increase orthogonal ribosome production as the demand for translational resources by a synthetic circuit increases. Our results highlight the potential of dynamic translational resource allocation as a means of minimising the impact of cellular limitations on the function of synthetic circuitry.
A maladaptive combination of traits contributes to the maintenance of a stable hybrid zone between two divergent species ofDrosophila
Authors: Cooper Brandon S. , Sedghifar Alisa , Nash W. Thurston , Comeault Aaron A. , Matute Daniel R.
Published: May 2017

Geographical areas where two species come into contact and hybridize serve as natural laboratories for assessing mechanisms that limit gene flow between species. The ranges of about half of all closely relatedDrosophilaspecies overlap, and the genomes of several pairs reveal signatures of past introgression. However, only two contemporary hybrid zones have been characterized in the genus, and both are recently diverged sister species (D. simulans-D. sechellia, Ks = 0.05;D. yakuba-D. santomea, Ks = 0.048). Here we present evidence of a new hybrid zone, and the ecological mechanisms that maintain it, between two highly divergentDrosophilaspecies (Ks = 0.11). On the island of Bioko in west Africa,D. teissierioccupies mostly forests,D. yakubaoccupies mostly open agricultural areas, and recently, we discovered that hybrids between these species occur near the interface of these habitats. Genome sequencing revealed that all field-sampled hybrids are F1progeny ofD. yakubafemales andD. teissierimales. We found no evidence for either advanced-generation hybrids or F1hybrids produced byD. teissierifemales andD.yakubamales. The lack of advanced-generation hybrids on Bioko is consistent with mark-recapture and laboratory experiments that we conducted, which indicate hybrids have a maladaptive combination of traits. LikeD. yakuba, hybrids behaviorally prefer open habitat that is relatively warm and dry, but likeD. teissieri, hybrids have low desiccation tolerance, which we predict leaves them physiologically ill-equipped to cope with their preferred habitat. These observations are consistent with recent findings of limited introgression in theD. yakubaclade and identify an ecological mechanism for limiting gene flow betweenD. yakubaandD. teissieri; namely, selection against hybrids that we have documented, in combination with hybrid male sterility, contributes to the maintenance of this narrow (~30m), stable hybrid zone centered on the forest-open habitat ecotone. Our results show how a deleterious combination of parental traits can result in unfit or maladapted hybrids.
Complex interaction of resource availability, life-history and demography determines the dynamics and stability of stage-structured populations
Authors: Tung Sudipta , Rajamani M. , Joshi Amitabh , Dey Sutirth
Published: May 2017

The dynamics of stage-structured populations facing variability in resource availability and/or demographic factors like unequal sex-ratios, remains poorly understood. We addressed these issues using a stage-structured individual-based model that incorporates life-history parameters common to many holometabolous insects. The model was calibrated using time series data from a 49-generation experiment on laboratory populations ofDrosophila melanogaster, subjected to four different combinations of larval and adult nutritional levels. The model was able to capture multiple qualitative and quantitative aspects of the empirical time series across three independent studies. We then simulated the model to explore the interaction of various life-history parameters and nutritional levels in determining population stability. In all nutritional regimes, stability of the populations was reduced upon increasing egg-hatchability, critical mass and proportion of body resource allocated to female fecundity. However, the stability-effects of increasing sensitivity of female-fecundity to adult density varied across nutrition regimes. The effects of unequal sex-ratio and sex-specific culling were greatly influenced by fecundity but not by levels of juvenile nutrition. Finally, we investigated the implications of some of these insights on the efficiency of the widely-used pest control method, Sterile Insect Technique (SIT). We show that increasing the amount of juvenile food had no effects on SIT efficiency when the density-independent fecundity is low, but reduces SIT efficiency when the density-independent fecundity is high.