bluuebunny/crossref_metadata_2025 huggingface dataset:
LEFT—A web‐based tool for the remote measurement and estimation of ecological value across global landscapes
Authors: Long Peter R. , Benz David , Martin Andrew C. , Holland Philip W. A. , Macias‐Fauria Marc , Seddon Alistair W. R. , Hagemann Randi , Frost Tone K. , Simpson Andrew , Power David J. , Slaymaker Mark A. , Willis Kathy J.
Published: October 2017

The overall aim in the development of the Local Ecological Footprinting Tool (LEFT) was to design a web‐based tool that could provide quickly obtained quantitative data on ecological risk to assist landowners when making land‐use change decisions.

The Local Ecological Footprinting Tool works for almost any region in the world and uses freely available satellite imagery, biotic and abiotic data from existing global databases, models and algorithms to deliver a customised report for a selected area within one hour of job submission.

Biotic data automatically obtained for a selected landscape includes terrestrial vertebrate and plant species occurrence data, information on their conservation status and remotely sensed vegetation productivity. Abiotic information obtained includes temperature, precipitation, water availability, insolation, topography, elevation, distribution of urban infrastructure and location of wetlands.

The tool performs a number of analyses on the biotic and abiotic data to produce maps for the selected area at a 30 m resolution depicting land cover type, numbers of globally threatened terrestrial vertebrate and plant species, beta‐diversity of terrestrial vertebrates and plants, habitat intactness, wetland habitat connectivity, numbers of migratory species and vegetation resilience. Results are also aggregated to produce a summary map demonstrating areas of high and low ecological risk across the selected area.

The Local Ecological Footprinting Tool has been designed to be intuitive to use, requiring no specialised software or user expertise. Input is extremely easy and requires the user to highlight the area of interest on a map or using grid co‐ordinates. Output is delivered via the web application and comprises a customised PDF containing the maps and a zip file of geographical information system (GIS) data for the area requested. Users may run an unlimited number of LEFT analyses and download reports free of charge. In addition to the free tool described in this paper, there is also a paid service: individual LEFT analyses can be upgraded for a charge to allow access to the geographically subsetted datasets generated for each report. These data are supplied as a zip file containing raster datasets for the layers in the LEFT analysis in GeoTIFF format. These can be opened and queried in a GIS software package.
Air Ambulance Delivery and Administration of Four‐factor Prothrombin Complex Concentrate Is Feasible and Decreases Time to Anticoagulation Reversal
Authors: Vines Claire , Tesseneer Stephanie J. , Cox Robert D. , Darsey Damon A. , Carbrey Kristin , Puskarich Michael A.
Published: October 2017

Objectives

The objective was to evaluate the feasibility, safety, and preliminary efficacy of four‐factor prothrombin complex concentrate (4‐factor PCC) administration by an air ambulance service prior to or during transfer of patients with warfarin‐associated major hemorrhage to a tertiary care center for definitive management (interventional arm) compared to patients receiving 4‐factor PCC following transfer by air ambulance or ground without 4‐factor PCC treatment (conventional arm).

Methods

This was a retrospective chart review of patients presenting to a large academic medical center. All patients presenting to the emergency department (ED) treated with 4‐factor PCC from April 1, 2014, through June 30, 2016, were identified. For this study, only transfer patients with an International Normalized Ratio (INR) > 1.5 actively treated with warfarin were included. The primary outcome was the proportion of patients with an INR ≤ 1.5 upon tertiary care hospital arrival, and the secondary efficacy outcome was difference in time to achievement of INR ≤ 1.5. Additional safety and efficacy objectives included difference in thromboembolic complications, length of stay, intensive care unit length of stay, and inpatient mortality between groups.

Results

Of the 72 included patients, a higher proportion of patients in the interventional group had an INR ≤ 1.5 on ED arrival (proportion difference = 0.82, 95% confidence interval = 0.64–0.92, p < 0.0001) and significantly reduced time to observed INR ≤ 1.5 (181 minutes vs. 541 minutes, p = 0.001). No differences were observed in thromboembolic complications or patient‐centered outcomes with the exception of mortality, which was significantly higher in patients in the interventional group. This group was also observed to have lower Glasgow Coma Scale score and higher intubation rates prior to transfer and treatment.

Conclusions

Dispatch of an air ambulance carrying 4‐factor PCC with administration prior to transfer is feasible and leads to more rapid improvement in INR among patients with warfarin‐associated major hemorrhage.
Gestational tissue inflammatory biomarkers at term labor: A systematic review of literature
Authors: Hadley Emily E. , Richardson Lauren S. , Torloni Maria R. , Menon Ramkumar
Published: October 2017

Parturition at term is characterized by inflammatory overload in both feto‐maternal tissues. Despite the large number of individual studies on changes in inflammatory biomarkers linked to labor, a comprehensive profile of them in each of the uterine compartments is not available to better understand their mechanistic contributions to labor. This systematic review investigated the pro‐ and anti‐inflammatory biomarkers reported in intra‐uterine tissues (amnion, chorion, decidua, placenta, and myometrium) at term labor. We conducted a systematic review of studies on pro‐ and anti‐inflammatory biomarkers (mRNA and/or protein) reported in feto‐maternal tissues during normal human term labor, published in English (1980‐2016), in 3 electronic data bases. From a total of 3712 citations, 172 were included for final review. Each tissue expresses a unique set of biomarkers at the time of term labor, but there is significant overlap between tissues. All tissues had IL‐6, IL‐8, IL‐1β, COX‐2, PGE‐2, TNF‐α, and hCAP18 in common at term labor. Common and unique inflammatory biomarkers are expressed in various feto‐maternal compartments at term labor. Increase in pro‐inflammatory markers in all gestational tissue signifies their harmonious functional role in promoting labor. Anti‐inflammatory markers at term labor are hardly reported.
Robotic surgery for the upper gastrointestinal tract: Current status and future perspectives
Authors: Nakauchi Masaya , Uyama Ichiro , Suda Koichi , Mahran Mohamed , Nakamura Tetsuya , Shibasaki Susumu , Kikuchi Kenji , Kadoya Shinichi , Inaba Kazuki
Published: October 2017

More than 4000 da Vinci Surgical Systems have been installed worldwide. Robotic surgery using the da Vinci Surgical System has been increasingly performed in the last decade, especially in urology and gynecology. The da Vinci Surgical System has not become standard in surgery of the upper gastrointestinal tract because of a lack of clear benefits in comparison with conventional minimally invasive surgery. We initiated robotic gastrectomy and esophagectomy for patients with upper gastrointestinal cancer in 2009, and we have demonstrated the potential advantages of the da Vinci Surgical System in reducing postoperative local complications after gastrectomy and recurrent laryngeal nerve palsy after esophagectomy. However, robotic surgery has the disadvantages of a longer operative time and higher costs than the conventional approach. In this review article, we present the current status of robotic surgery for gastric and esophageal cancer, as well as future perspectives on this approach, based on our experience and a review of the literature.
Elevated serum creatinine and hyponatraemia as prognostic factors in canine acute pancreatitis
Authors: Marchetti V , Gori E , Lippi I , Luchetti E , Manca ML , Pierini A
Published: October 2017

Objective

To evaluate prognostic factors for canine acute pancreatitis (AP) based on clinical and laboratory data that can be easily assessed in veterinary practice.

Design

Retrospective study between January 2010 and December 2013.

Methods

The diagnosis of AP was based on clinical signs and an abnormal SNAP® cPL™ test result, concurrently with an ultrasound pattern suggestive of pancreatitis. Dogs were divided into survivors and non‐survivors. We evaluated 12 clinical and laboratory parameters: respiratory rate, rectal temperature, white blood cells, haematocrit, total serum proteins, albumin, creatinine, cholesterol, total and ionised calcium, sodium and potassium. Clinical and clinicopathological data were statistically compared between survivors and non‐survivors. A value of P < 0.05 was considered significant and P < 0.01 as highly significant. The odds ratio (OR) was calculated.

Results

The study enrolled 50 client‐owned dogs with a diagnosis of AP. Serum creatinine (P = 0.017) and sodium (P = 0.004) correlated significantly with the outcome.Serum sodium < 139.0 mmol/L (139.0 mEq/L) and serum creatinine > 212 μmol/L (2.4 mg/dL) were associated significantly with poor prognosis. Azotaemia (OR 12.5; 95% confidence interval (CI) 1.32–118.48) and hyponatraemia (OR 4.9; 95% CI 1.36–17.64) were associated with increased risk of death.

Conclusions

In dogs with AP, hyponatraemia and azotaemia seem to be significantly associated with an increased risk of death.
Horse‐keeping practices in Australia: findings from a national online survey of horse owners
Authors: Thompson KR , Clarkson L , Riley CB , van den Berg M
Published: October 2017

Objective

To gain an understanding of general horse‐keeping practices in Australia, including shelter, social contact, exercise, watering and supplementary feeding.

Methods

An online survey was conducted with 505 owners in relation to one ‘representative’ horse in their care.

Results

The majority (83%) of horses were managed at pasture. Approximately one‐quarter of those horses were housed alone (26%) or with one companion animal (27%). If horses were confined to a stable or small yard, the most recorded means of exercise was riding (65%) at a daily frequency (60%). Over half of the horse owners provided water in a trough or drinker with an automatic refill system (58%) and most horse owners supplied hay to their horses (82%), most commonly in combination with grazing. Areas of potential concern included one‐quarter of stabled horses being prevented from unmediated social and physical contact with conspecifics and one‐fifth of stabled horses being exercised less than daily.

Conclusion

The horse‐keeping profile in this study should be considered in the public communication of guidelines as well as interactions between veterinarians and clients.
Examination of the use of intraovarian administration of CaCl2 and zinc gluconate as potential chemosterilants in Bos indicus heifers
Authors: Cavalieri J , Hayes L
Published: October 2017

Objective

To investigate if administration of potential chemosterilants by transvaginal, ultrasound‐guided intraovarian injection is an alternative to surgical sterilisation.

Design

Randomised control study.

Methods

Bos indicus heifers were treated with intraovarian injections of saline (n = 10), CaCl2 (n = 10), zinc gluconate (ZG; n = 10) or a combination of CaCl2 and ZG (CaCl2 + ZG; n = 10). Heifers were exposed to a bull from 82 to 84 days after treatment and slaughtered between 364 and 396 days after treatment.

Results

After treatment administration, the concentrations of haptoglobin and anti‐Müllerian hormone and the total oocyte counts did not differ (P > 0.150) between treatments. Pain responses were observed in heifers treated with ZG and CaCl2 + ZG but not in heifers treated with saline or CaCl2. Total ovarian mass at slaughter was less in heifers treated with CaCl2 compared with the other treatments (P < 0.05). Complete regression of one ovary was observed in 40% (4/10) of the heifers treated with CaCl2. Pregnancies were recorded in ≥ 70% of heifers administered each treatment.

Conclusion

Treatments used in this study were not able to sterilise most of the B. indicus heifers, but treatment with CaCl2 has the potential to cause complete ovarian atrophy without causing detectable pain.
Population pharmacokinetics of exendin‐(9‐39) and clinical dose selection in patients with congenital hyperinsulinism
Authors: Ng Chee M. , Tang Fei , Seeholzer Steven H. , Zou Yixuan , De León Diva D.
Published: October 2017

Aims

Congenital hyperinsulinism (HI) is the most common cause of persistent hypoglycaemia in infants and children. Exendin‐(9‐39), an inverse glucagon‐like peptide 1 (GLP‐1) agonist, is a novel therapeutic agent for HI that has demonstrated glucose‐raising effect. We report the first population pharmacokinetic (PopPK) model of the exendin‐(9‐39) in patients with HI and propose the optimal dosing regimen for future clinical trials in neonates with HI.

Methods

A total of 182 pharmacokinetic (PK) observations from 26 subjects in three clinical studies were included for constructing the PopPK model using first order conditional estimation (FOCE) with interaction method in nonlinear mixed‐effects modelling (NONMEM). Exposure metrics (area under the curve [AUC] and maximum plasma concentration [Cmax]) at no observed adverse effect levels (NOAELs) in rats and dogs were determined in toxicology studies.

Results

Observed concentration–time profiles of exendin‐(9‐39) were described by a linear two‐compartmental PK model. Following allometric scaling of PK parameters, age and creatinine clearance did not significantly affect clearance. The calculated clearance and elimination half‐life for adult subjects with median weight of 69 kg were 11.8 l h−1 and 1.81 h, respectively. The maximum recommended starting dose determined from modelling and simulation based on the AUC0‐last at the NOAEL and predicted AUC0‐inf using the PopPK model was 27 mg kg−1 day−1 intravenously.

Conclusions

This is the first study to investigate the PopPK of exendin‐(9‐39) in humans. The final PopPK model was successfully used with preclinical toxicology findings to propose the optimal dosing regimen of exendin‐(9‐39) for clinical studies in neonates with HI, allowing for a more targeted dosing approach to achieve desired glycaemic response.
Stress and skin disease quality of life: the moderating role of anxiety sensitivity social concerns
Authors: Dixon L.J. , Witcraft S.M. , McCowan N.K. , Brodell R.T.
Published: October 2017

Background

Stress is an important factor in the onset, exacerbation and reoccurrence of many skin diseases. Little is known about psychological risk factors that affect the association between stress and dermatological conditions. One relevant factor that may modulate this link is anxiety sensitivity (AS) social concerns – the propensity to respond fearfully to anxiety-related sensations (e.g. sweating, flushing) owing to perceived social consequences (e.g. rejection or humiliation).

Objectives

To gain insight into psychological factors affecting skin disease, we examined the moderating role of AS social concerns in the relationship between stress and skin disease quality of life (QoL).

Methods

Participants [n = 237 (161 female), mean ± SD age 34·18 ± 9·57 years] with active skin disease symptoms were recruited online and completed questionnaires assessing stress, AS social concerns, skin disease QoL and global skin disease symptom severity.

Results

AS social concerns moderated the association between stress and skin-related emotional and social functioning in adults with skin disease. Stress was a significant predictor of the impairment associated with skin disease.

Conclusions

Stress was linked to skin disease-related emotional and functional impairment associated with skin disease among individuals with high AS social concerns. These results highlight the potential for AS reduction interventions to break the vicious cycle of stress and skin disease symptoms and to improve psychosocial well-being in dermatology patients.
Current challenges and opportunities in treating adult patients with Philadelphia‐negative acute lymphoblastic leukaemia
Authors: Wolach Ofir , Amitai Irina , DeAngelo Daniel J.
Published: October 2017

Significant advances have been made in recent years in the field of Philadelphia‐negative acute lymphoblastic leukaemia (ALL). New insights into the biology and genetics of ALL as well as novel clinical observations and new drugs are changing the way we diagnose, risk‐stratify and treat adult patients with ALL. New genetic subtypes and alterations refine risk stratification and uncover new actionable therapeutic targets. The incorporation of more intensive, paediatric and paediatric‐inspired approaches for young adults seem to have a positive impact on survival in this population. Minimal residual disease at different time points can assist in tailoring risk‐adapted interventions for patients based on individual response. Finally, novel targeted approaches with monoclonal antibodies, immunotherapies and small molecules are moving through clinical development and entering the clinic. The aim of this review is to consolidate the abundance of emerging data and to review and revisit the concepts of risk‐stratification, choice of induction and post‐remission strategies as well as to discuss and update the approach to specific populations with ALL, such as young adult, elderly/unfit and relapsed/refractory patients with ALL.
Donor‐derivedCD19‐targeted T cell infusion induces minimal residual disease‐negative remission in relapsed B‐cell acute lymphoblastic leukaemia with no response to donor lymphocyte infusions after haploidentical haematopoietic stem cell transplantation
Authors: Chen Yuhong , Cheng Yifei , Suo Pan , Yan Chenhua , Wang Yu , Chen Yao , Han Wei , Xu Lanping , Zhang Xiaohui , Liu Kaiyan , Chang Lungji , Xiao Lei , Huang Xiaojun
Published: October 2017

Relapse is a common cause of failure in patients with B‐cell acute lymphoblastic leukaemia (B‐ALL) after haploidentical haematopoietic stem cell transplantation (haplo‐HSCT), and non‐responders to donor lymphoblastic infusion afterHSCThave a very poor prognosis. Although donor‐derivedCD19‐directed chimeric antigen receptor‐modified (CAR) T cells can potentially cure leukaemia, their effectiveness and safety have not been confirmed in relapsed B‐ALLcases after haplo‐HSCT. Between January 2015 and January 2017, two and four patients each received one and two infusions ofCART cells from haplo‐HSCTdonors. Five (83·33%) achieved minimal residual disease (MRD)‐negative remission; one patient was discharged automatically without evaluation after developing severe thrombotic microangiopathies. Four of five responsive patients relapsed after 2–7 months, and one died of sepsis followingMRD‐negative remission after a second infusion. None of the other second infusion recipients achieved a second complete remission. Five patients (83·33%) experienced eight courses of grade 1–3 cytokine release syndrome; two were treated with tocilizumab. Two (33·3%) and one patient developed grade 2 and 3 acute graft‐versus‐host disease (aGVHD), respectively; the former was controlled with glucocorticoids. Donor‐derivedCART‐cell infusion seems be effective and safe for relapsed B‐ALLafter haplo‐HSCT, although larger clinical studies are needed.
Association between maternal haemoglobin and stillbirth: a cohort study among a multi‐ethnic population in England
Authors: Nair Manisha , Churchill David , Robinson Susan , Nelson‐Piercy Cathy , Stanworth Simon J. , Knight Marian
Published: October 2017

The study objectives were to examine the association of maternal haemoglobin with stillbirth and perinatal death in a multi‐ethnic population in England. We conducted a retrospective cohort analysis using anonymised maternity data from 14 001 women with singleton pregnancies ≥24 weeks’ gestation giving birth between 2013 and 2015 in two hospitals ‐ the Royal Wolverhampton NHS Trust and Guy's and St Thomas’ NHS Foundation Trust. Multivariable logistic regression analyses were undertaken to analyse the associations between maternal haemoglobin at first visit and at 28 weeks with stillbirth and perinatal death, adjusting for 11 other risk factors. Results showed that 46% of the study population had anaemia (haemoglobin <110 g/l) at some point during their pregnancy. The risk of stillbirth and perinatal death decreased linearly per unit increase in haemoglobin concentration at first visit (adjusted odds ratio [aOR] stillbirth = 0·70, 95% confidence interval [CI] 0·58–0·85, aOR perinatal death = 0·71, 95% CI 0·60–0·84) and at 28 weeks (aOR stillbirth = 0·83, 95% CI 0·66–1·04; aOR perinatal death = 0·86, 95%CI 0·67–1·12). Compared with women with haemoglobin ≥110 g/l, the risk of stillbirth and perinatal death was five‐ and three‐fold higher in women with moderate‐severe anaemia (haemoglobin <100 g/l) at first visit and 28 weeks, respectively. These findings have clinical and public health importance.
A phase 1 clinical trial evaluating marizomib, pomalidomide and low‐dose dexamethasone in relapsed and refractory multiple myeloma (NPI‐0052‐107): final study results
Authors: Spencer Andrew , Harrison Simon , Zonder Jeffrey , Badros Ashraf , Laubach Jacob , Bergin Krystal , Khot Amit , Zimmerman Todd , Chauhan Dharminder , Levin Nancy , MacLaren Ann , Reich Steven D. , Trikha Mohit , Richardson Paul
Published: October 2017

Marizomib (MRZ) is an irreversible, pan‐subunit proteasome inhibitor (PI) in clinical development for relapsed/refractory multiple myeloma (RRMM) and glioma. This study analysed MRZ, pomalidomide (POM) and low‐dose dexamethasone (Lo‐DEX) [PMD] in RRMM to evaluate safety and determine the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D). Intravenous MRZ (0·3–0·5 mg/m2) was administered over 2 h on days 1, 4, 8, 11; POM (3–4 mg) on days 1–21; and Lo‐DEX (5 or 10 mg) on days 1, 2, 4, 5, 8, 9, 11, 12, 15, 16, 22 and 23 of every 28‐day cycle. Thirty‐eight patients were enrolled that had received a median of 4 (range 1–10) prior lines of therapy; all patients received prior lenalidomide and bortezomib. No dose‐limiting toxicities (DLTs) were observed and 0·5 mg/m2 MRZ was determined to be the RP2D. The most common treatment‐related ≥Grade 3 adverse events were: neutropenia (11/38 patients: 29%), pneumonia (4/38 patients 11%), anaemia (4/38 patients; 11%) and thrombocytopenia (4/38 patients; 11%). The overall response rate and clinical benefit rate was 53% (19/36) and 64% (23/36), respectively. In conclusion, PMD was well tolerated and demonstrated promising activity in heavily pre‐treated, high‐risk RRMM patients.
Minimal residual disease in non‐Hodgkin lymphoma – current applications and future directions
Authors: Chase Matthew L. , Armand Philippe
Published: October 2017

Non‐Hodgkin Lymphomas (NHLs) are a heterogeneous group of tumours with distinct treatment paradigms, but in all cases the goal of treatment is to maximize quality and duration of remission while minimizing therapy‐related toxicity. Identification of persistent disease or relapse is most often the trigger to intensify or re‐initiate anti‐neoplastic therapy, respectively. In the current era of NHL treatment, this determination is mostly based on imaging and clinical evaluations, tools with imperfect sensitivity and specificity. The availability of minimal residual disease (MRD) monitoring could transform treatment paradigms by allowing intensification of treatment in at‐risk patients or early intervention for impending relapse. Novel methods based on polymerase chain reaction and next‐generation sequencing are now being studied in NHL with promising results. This review outlines the current status of the field in the use of MRD techniques for diffuse large B‐cell lymphoma, mantle cell lymphoma and follicular lymphoma. Specifically, we address their demonstrated and potential clinical utility in risk stratification, monitoring of remission status, and guiding interim and post‐treatment escalation. Future applications of these techniques could identify novel markers of MRD, improve initial treatment selection, guide treatment escalation or de‐escalation, and allow for real‐time monitoring of patterns of clonal evolution, which together could redefine NHL treatment paradigms.
Dual inhibition of the mTORC1 and mTORC2 signaling pathways is a promising therapeutic target for adult T‐cell leukemia
Authors: Kawata Takahito , Tada Kohei , Kobayashi Masayuki , Sakamoto Takashi , Takiuchi Yoko , Iwai Fumie , Sakurada Maki , Hishizawa Masakatsu , Shirakawa Kotaro , Shindo Keisuke , Sato Hironori , Takaori‐Kondo Akifumi
Published: October 2017

Adult T‐cell leukemia (ATL) has a poor prognosis as a result of severe immunosuppression and rapid tumor progression with resistance to conventional chemotherapy. Recent integrated‐genome analysis has revealed mutations in many genes involved in the T‐cell signaling pathway, suggesting that the aberration of this pathway is an important factor in ATL pathogenesis and ATL‐cell proliferation. We screened a siRNA library to examine signaling‐pathway functionality and found that the PI3K/Akt/mTOR pathway is critical to ATL‐cell proliferation. We therefore investigated the effect of mammalian target of rapamycin (mTOR) inhibitors, including the dual inhibitors PP242 and AZD8055 and the mTORC1 inhibitors rapamycin and everolimus, on human T‐cell leukemia virus type 1 (HTLV‐1)‐infected‐cell and ATL‐cell lines. Both dual inhibitors inhibited the proliferation of all tested cell lines by inducing G1‐phase cell‐cycle arrest and subsequent cell apoptosis, whereas the effects of the 2 mTORC1 inhibitors were limited, as they did not induce cell apoptosis. In the ATL‐cell lines and in the primary ATL samples, both dual inhibitors inhibited phosphorylation of AKT at serine‐473, a target of mTORC2, as well as that of S6K, whereas the mTORC1 inhibitors only inhibited mTORC1. Furthermore, AZD8055 more significantly inhibited the in vivo growth of the ATL‐cell xenografts than did everolimus. These results indicate that the PI3K/mTOR pathway is critical to ATL‐cell proliferation and might thus be a new therapeutic target in ATL.
Perspectives on the discovery of NOTCH2‐specific inhibitors
Authors: Dobranowski Peter , Ban Fuqiang , Contreras‐Sanz Alberto , Cherkasov Artem , Black Peter C.
Published: October 2017

The Notch pathway is a cell‐cell communication system where membrane‐bound ligands interact with the extracellular region of Notch receptors to induce intracellular, downstream effects on gene expression. Aberrant Notch signaling promotes tumorigenesis, and the Notch pathway has tremendous potential for novel targeting strategies in cancer treatment. While γ‐secretase inhibitors as Notch‐inhibiting agents are already promising in clinical trials, they are highly non‐specific with adverse side‐effects. One of the underlying challenges is that two of the four known human Notch paralogs, NOTCH1 and 2, share very high structural similarity but play opposing roles in some tumorigenesis pathways. This perspective explores the feasibility of developing Notch‐specific small molecule inhibitors targeting the anti‐NOTCH2 antibody‐binding epitopes or the “S2‐Leu‐plug‐binding site” using a computer‐aided drug discovery approach.
An Experimental Investigation of Antisocial Lie‐Telling Among Children With Disruptive Behavior Disorders and Typically Developing Children
Authors: Mugno Allison P. , Malloy Lindsay C. , Waschbusch Daniel A. , Pelham Jr. William E. , Talwar Victoria
Published: October 2017

Children's lie‐telling is surprisingly understudied among children with significant behavioral problems. In the present study, experimental paradigms were used to examine antisocial lie‐telling among ethnically diverse 5‐ to 10‐year‐old children with disruptive behavior disorders (DBD; n = 71) and a typically developing (TD) comparison sample (n = 50) recruited from a southeastern state from 2013 to 2014. Children completed two games that measured the prevalence and skill of their lies: (a) for personal gain and (b) to conceal wrongdoing. Children with DBD were more likely to lie for personal gain than TD children. With age, children were more likely to lie to conceal wrongdoing, but the reverse was true regarding lies for personal gain. Results advance knowledge concerning individual differences in children's lie‐telling.
Bone mineral density in familial partial lipodystrophy
Authors: Fernández‐Pombo Antía , Ossandon‐Otero Javier A. , Guillín‐Amarelle Cristina , Sánchez‐Iglesias Sofía , Castro Ana I. , González‐Méndez Blanca , Rodríguez‐García Silvia , Rodriguez‐Cañete Leticia , Casanueva Felipe F. , Araújo‐Vilar David
Published: October 2017

Objective

Type 1 and type 2 familial partial lipodystrophies (FPLD) are characterized by the loss or increase in subcutaneous fat in certain body regions, as well as metabolic disorders. Higher muscle volume and mass have also been described. However, so far, possible bone involvement has not been studied. The aim of this study was to evaluate bone mineral density (BMD) in patients with type 1 and type 2 FPLD.

Methods

A total of 143 women were selected and distributed into three groups (17 women with FPLD2, 82 women with FPLD1 and 44 nonlipodystrophic obese female controls). A thorough history and physical examination were carried out on all subjects, as well as the measurement of anthropometric features. BMD along with fat and fat‐free mass (FFM) were determined by DXA (dual‐energy X‐ray absorptiometry). Statistical analyses, primarily using the χ2, ANOVA and ANCOVA tests, were performed, using age, height, fat and FFM as covariables.

Results

After eliminating the possible influences of age, height, fat and FFM, we observed that there were no significant differences in total BMD between patients with FPLD and the control group, showing total BMD values of 1.092 ± 0.037 g/cm2 in the FPLD2 group, 1.158 ± 0.013 g/cm2 in the FPLD1 group and 1.173 ± 0.018 g/cm2 in the control group (P = .194). Similarly, no significant differences were found in segmental BMD.

Conclusions

Unlike in other types of laminopathy in which bone is affected, in the case of FPLD, there are no differences in BMD compared to nonlipodystrophic subjects.
UK trends of allergic occupational skin disease attributed to fragrances 1996–2015
Authors: Montgomery Rachel L. , Agius Raymond , Wilkinson Stephen M. , Carder Melanie
Published: October 2017

Background

Fragrances are well known to cause allergic contact dermatitis (ACD). Occupationally related cases occur, with certain groups being at higher risk.

Objective

To investigate the incidence of occupationally related cases of cutaneous fragrance allergy and to evaluate trends.

Method

Data on incident cases of occupational ACD caused by fragrances between 1996 and 2015 (inclusive) reported to the EPIDERM surveillance scheme were analysed.

Results

Of the cases reported to EPIDERM during the study period, 5.2% had ACD attributed to fragrances. The highest annual incidence rates were observed in women. Hairdressers, beauticians and people working in related occupations had a 47‐fold higher incidence rate ratio than the reference category (the average of all other occupations combined). Trends analysis suggested a non‐significant increase in fragrance allergy over the study period among all occupations, and beauty and food workers, and a slight decrease in healthcare workers.

Conclusions

Fragrance allergy is a significant problem in an occupational setting. Although there was no significant change in the incidence of fragrance‐related allergic occupational contact dermatitis (OCD) during the 20‐year study period, this does not mirror the trend in OCD, which is falling. Fragrance allergy continues to be a major contributor to OCD, and contributes to a greater proportion of cases.
Denosumab‐induced cutaneous hypersensitivity reaction with distinct clinical and histopathologic findings
Authors: King Brian J. , Lehman Julia S. , Sartori Valinotti Julio C.
Published: October 2017

Cutaneous reactions from targeted biologics are increasingly common. We describe a case of a cutaneous lichenoid drug eruption from the RANK inhibitor denosumab and a previously unreported lymphohistiocytic reaction pattern. The clinical and histopathological details of this case will aid in recognition, diagnosis, and treatment of drug rashes from denosumab.
Invasion lags: The stories we tell ourselves and our inability to infer process from pattern
Authors: Coutts Shaun R. , Helmstedt Kate J. , Bennett Joseph R.
Published: October 2017

Aim

Many alien species experience a lag phase between arriving in a region and becoming invasive, which can provide a valuable window of opportunity for management. Our ability to predict which species are experiencing lags has major implications for management decisions that are worth billions of dollars and that may determine the survival of some native species. To date, timing and causes of lag and release have been identified post hoc, based on historical narratives.

Location

Global.

Methods

We use a simple but realistic simulation of population spread over a fragmented landscape. To break the invasion lag, we introduce a sudden, discrete change in dispersal.

Results

We show that the ability to predict invasion lags is minimal even under controlled circumstances. We also show a non‐negligible risk of falsely attributing lag breaks to mechanisms based on invasion trajectories and coincidences in timing.

Main conclusions

We suggest that post hoc narratives may lead us to erroneously believe we can predict lags and that a precautionary approach is the only sound management practice for most alien species.
A rare case of “subcommissural adhesive aortic stenosis”: Triangular struggle of aortic valve area, hemodynamics, and calcium burden
Authors: Matsuzoe Hiroki , Matsumoto Kensuke , Mori Shumpei , Toba Takayoshi , Kawamori Hiroyuki , Shimoyama Shinsuke , Tanaka Hidekazu , Shinke Toshiro , Hirata Ken‐ichi
Published: October 2017

This report concerns an 83‐year‐old woman with aortic stenosis (AS) who had a history of repetitive hospitalization due to decompensated heart failure. Although her clinical history was compatible with significant AS, findings for aortic valve area, hemodynamics, and valvular calcium burden were discrepant. Multiplanar reconstruction images revealed the membranous structures attached to a subcommissural lesion, which resulted in severe stenosis. The patient had a favorable clinical course after transcatheter aortic valve replacement. This is the first reported case of severe AS due to the subcommissural adhesions, which were successfully visualized by means of echocardiography and computed tomography.
Police Violence and the Underreporting of Crime
Authors: Gingerich Daniel W. , Oliveros Virginia
Published: October 2017

This paper examines the relationship between police violence and the reporting of crime. Utilizing original data from a large‐scale household survey conducted in Costa Rica from October 2013 to April 2014 (n = 4,200), we find that the observation of police violence significantly reduces citizens’ willingness to report crime. The implications of this finding are explored using a game‐theoretic model of crime, crime reporting, and police misconduct. The model reveals that although the prospect of police violence against criminals may generate a degree of deterrence for criminal behavior, permissiveness toward police violence also raises expectations about the likelihood of police abuse against law‐abiding citizens. Consistent with our empirics, this reduces citizens’ propensity to report crime, thereby fostering a climate of impunity for criminal activity.
Intersecting disadvantage: Unpacking poor outcomes within early intervention in psychosis services
Authors: Jones Nev , Godzikovskaya Julia , Zhao Zhen , Vasquez Anthony , Gilbert Al , Davidson Larry
Published: October 2017

Aim

In order to strengthen specialized early intervention in psychosis (EIP) services, a contextually nuanced understanding of psychosocial forces driving suboptimal treatment response is critical. This study sought to examine factors driving poor outcomes through a systematic emic coding of psychosocial assessments for discharged EIP clients categorized as leaving with all treatment goals met (AG) or no treatment goals met (NG).

Methods

Psychosocial assessments at baseline, 1 year, 2 years and discharge were extracted from an EIP research registry and systematically coded. One hundred and thirty clients met the study's inclusion criteria (72 NG, 58 AG) from a larger pool of 278. Assessments were coded, quantized and analysed using a combination of basic inferential statistics and thematic analysis.

Results

Structural adversity, individual trauma, history of aggression/violence, limited insight and long treatment histories prior to EIP, were strong and significant predictors of poor client outcomes (NG), while motivation for treatment, college goals or preparedness at baseline, baseline engagement in constructive activities, social strengths, individual strengths, talents and family support strongly predicted better outcomes (AG). Race/ethnicity also significantly predicted outcome group. Analyses underscore the powerful impact of multiple converging forms of structural disadvantage, on the one hand, and individual, family and social strengths and supports on the other, in shaping clients’ response to EIP treatment.

Conclusions

Findings emphasize the importance of greater empirical attention to background structural and socio‐economic conditions among early psychosis clients and their multifaceted impacts and underscore the potential value of programmatic components explicitly designed to support clients from multiply disadvantaged backgrounds.
Recurrent adnexal lymphoma in a horse
Authors: Martabano B. B. , Brooks D. E. , Whitley R. D. , Proietto L. R. , Conway J. A. , Zoll W. M. , Plummer C. E.
Published: October 2017

Lymphoma is a relatively uncommon neoplasm in the horse; however, it is considered the most common neoplasia of the equine haemolymphatic system. Limited reports of adnexal lymphoma have been documented in the literature, with no known reports of recurrence nearly a decade after mass excision. The objective is to describe a case of recurrent adnexal lymphoma in a 20‐year‐old Quarter Horse gelding presented to the Ophthalmology service at the University of Florida Veterinary Hospital (UFVH) for evaluation of a solitary subconjunctival mass of the right eye (OD). A focal, pink, fleshy mass associated with the dorsomedial bulbar conjunctiva was noted. An excisional biopsy was performed. Histopathology revealed lymphoma with clean margins. The client declined staging and further therapy at the initial visit. Approximately 8 years later, the horse began to exhibit intermittent mild to moderate diffuse swelling of the conjunctiva OD. Six months after onset, the swelling worsened acutely and was accompanied by severe swelling of the left conjunctiva (OS). The horse then returned to UFVH and was diagnosed with diffuse, bilateral conjunctival lymphoma. Humane euthanasia was elected. T cell lymphoma was confirmed with immunohistochemistry performed post‐mortem. At necropsy, neoplastic tissue was observed throughout the adnexal and ocular tissues of both eyes and in the submandibular lymph nodes. Adnexal lymphoma is an uncommon neoplasm in the horse. To the authors’ knowledge, this is the first documentation of a nodular adnexal lymphoma that involved an 8‐year period without recurrence followed by development of diffuse, bilateral disease. Typically, surgical excision of the nodular form of lymphoma involving the extraocular tissues yields an improved prognosis compared with the diffuse form of the disease. Further investigation is necessary to determine if nodular forms of adnexal lymphoma represent early stages of diffuse extraocular or systemic disease.
The Radical SAM enzyme NirJ catalyzes the removal of two propionate side chains during heme d1 biosynthesis
Authors: Boss Linda , Oehme Ramona , Billig Susan , Birkemeyer Claudia , Layer Gunhild
Published: October 2017

Heme d1 is a modified tetrapyrrole playing an important role in denitrification by acting as the catalytically essential cofactor in the cytochrome cd1 nitrite reductase of many denitrifying bacteria. In the course of heme d1 biosynthesis, the two propionate side chains on pyrrole rings A and B of the intermediate 12,18‐didecarboxysiroheme are removed from the tetrapyrrole macrocycle. In the final heme d1 molecule, the propionate groups are replaced by two keto functions. Although it was speculated that the Radical S‐adenosyl‐l‐methionine (SAM) enzyme NirJ might be responsible for the removal of the propionate groups and introduction of the keto functions, this has not been shown experimentally, so far. Here, we demonstrate that NirJ is a Radical SAM enzyme carrying two iron–sulfur clusters. While the N‐terminal [4Fe‐4S] cluster is essential for the initial SAM cleavage reaction, it is not required for substrate binding. NirJ tightly binds its substrate 12,18‐didecarboxysiroheme and, thus, can be purified in complex with the substrate. By using the purified NirJ/substrate complex in an in vitro enzyme activity assay, we show that NirJ indeed catalyzes the removal of the two propionate side chains under simultaneous SAM cleavage. However, under the reaction conditions employed, no keto group formation is observed indicating that an additional cofactor or enzyme is needed for this reaction.
The influence of partial surface shot peening on fatigue crack growth behaviour of a high‐strength ferritic steel
Authors: Al‐Turaihi A. , Mehmanparast A. , Brennan F.
Published: October 2017

The effects of partial surface shot peening on the fatigue crack growth behaviour of a ferritic steel have been experimentally investigated in this paper. Dog‐bone specimens fabricated from Optim700QL were tested under tension‐tension fatigue loads. Three distinct extents of partial shot peening, with respect to the crack tip and specimen symmetry line, were tested. The fatigue crack growth results from these experiments have been compared with those obtained from the same specimen geometry but with no peening. The results show that the residual stress fields formed ahead of the initial notch tip due to the partial peening process play a significant role in the fatigue crack growth behaviour of the material and effectively result in accelerated crack propagation at the midwidth of the specimens. It has been shown in this study that partial peening can lead to a fatigue crack growth rate around twice as fast as that of the unpeened specimen.
Rethinking fatigue crack growth: Crack growth at constant R and strain energy
Authors: Walker K.
Published: October 2017

This paper is the first of a series attempting to apply my 57‐year experience with durability and damage tolerance of aerospace structures to answer the question; why, after 50 plus years, have we not reached agreement on the validity of current crack growth assumptions.

To address this question, new concepts are introduced and interpreted in terms of strain energy.

The tentative answer to the question is that when interpreted in terms these new concepts and strain energy, there are serious conceptual errors in the da/dn diagrams that make the data base very difficult to properly interpret.

The materials presented raise new questions and provide possible answers to old ones.
Cyanobacterial formation of intracellular Ca‐carbonates in undersaturated solutions
Authors: Cam N. , Benzerara K. , Georgelin T. , Jaber M. , Lambert J.‐F. , Poinsot M. , Skouri‐Panet F. , Moreira D. , López‐García P. , Raimbault E. , Cordier L. , Jézéquel D.
Published: October 2017

Cyanobacteria have long been thought to induce the formation of Ca‐carbonates as secondary by‐products of their metabolic activity, by shifting the chemical composition of their extracellular environment to conditions favoring mineral precipitation. Some cyanobacterial species forming Ca‐carbonates intracellularly were recently discovered. However, the environmental conditions under which this intracellular biomineralization process can occur and the impact of cyanobacterial species forming Ca‐carbonates intracellularly on extracellular carbonatogenesis are not known. Here, we show that these cyanobacteria can form Ca‐carbonates intracellularly while growing in extracellular solutions undersaturated with respect to all Ca‐carbonate phases, that is, conditions thermodynamically unfavorable to mineral precipitation. This shows that intracellular Ca‐carbonate biomineralization is an active process; that is, it costs energy provided by the cells. The cost of energy may be due to the active accumulation of Ca intracellularly. Moreover, unlike cyanobacterial strains that have been usually considered before by studies on Ca‐carbonate biomineralization, cyanobacteria forming intracellular carbonates may slow down or hamper extracellular carbonatogenesis, by decreasing the saturation index of their extracellular solution following the buffering of the concentration of extracellular calcium to low levels.
Insulin‐like growth factor II messenger RNA‐binding protein‐3 is an independent prognostic factor in uterine leiomyosarcoma
Authors: Yasutake Nobuko , Ohishi Yoshihiro , Taguchi Kenichi , Hiraki Yuka , Oya Masafumi , Oshiro Yumi , Mine Mari , Iwasaki Takeshi , Yamamoto Hidetaka , Kohashi Kenichi , Sonoda Kenzo , Kato Kiyoko , Oda Yoshinao
Published: October 2017

Aims

The aim of this study was to identify the prognostic factors of uterine leiomyosarcoma (ULMS).

Methods and results

We reviewed 60 cases of surgically resected ULMSs and investigated conventional clinicopathological factors, together with the expression of insulin‐like growth factor II messenger RNA‐binding protein‐3 (IMP3), hormone receptors and cell cycle regulatory markers by immunohistochemistry. Mediator complex subunit 12 (MED12) mutation analysis was also performed. Univariate analyses revealed that advanced stage (P < 0.0001), older age (P = 0.0244) and IMP3 expression (P = 0.0011) were significant predictors of a poor outcome. Multivariate analysis revealed advanced stage (P < 0.0001) and IMP3 (P = 0.0373) as independent predictors of a poor prognosis. Expressions of cell cycle markers and hormone receptors, and MED12 mutations (12% in ULMSs) were not identified as prognostic markers in this study.

Conclusions

IMP3 expression in ULMS could be a marker of a poor prognosis.
Foreigners and Inclusion in Academia
Authors: Ayala‐López Saray
Published: October 2017

This article discusses the category of foreigner in the context of academia. In the first part I explore this category and its philosophical significance. A quick look at the literature reveals that this category needs more attention in analyses of dimensions of privilege and disadvantage. Foreignness has peculiarities that demarcate it from other categories of identity, and it intersects with them in complicated ways. Devoting more attention to it would enable addressing issues affecting foreigners in academia that go commonly unnoticed. In the second part of the article I argue that current efforts to make academia a more inclusive environment should address the disadvantages that many foreign academics face. I focus on two senses of foreigner: working and living in a country that is not your country of origin, and being a nonnative speaker of the language in which you work.