bluuebunny/crossref_metadata_2025 huggingface dataset:
Real gates to virtual fields: Integrating online and offline ethnography in studying cannabis cultivation and reflections on the applicability of this approach in criminological ethnography more generally
Authors: Potter Gary R
Published: August 2017

This article explores the interplay between online and offline approaches in criminological ethnography. Criminology has come to embrace online research: in addition to offering numerous research benefits generic to the social sciences, the Internet offers solutions to various problems specific to active offender research. Furthermore, as many types of criminal or deviant behaviour increasingly have online aspects, so engaging in online research becomes both valid and vital to any meaningful ethnography. However, online approaches should be treated with caution: they are subject to their own limitations, and to rely on online methods as an alternative to traditional approaches can be as problematic as failing to embrace online research at all. Drawing on my experiences researching cannabis cultivation, I demonstrate some of the ways that offline and online methods complement one another. Online methods were useful in expanding my own study beyond the normal constraints of ethnography by generating a larger and more varied sample and providing access to more data than traditional ethnographic approaches. They were also essential for exploring the various online aspects of cannabis cultivation. But offline methods proved invaluable in accessing and recruiting respondents online and in providing the experience essential to participating in – and understanding – cultivation-related online interactions. Both approaches revealed findings not identified by the other, and research in each environment helped with understanding experiences and observations in the other. I argue that while there are clear strengths in online approaches to criminological ethnography, certain pitfalls arise when online techniques are used without employing face-to-face research as well. Triangulation of online and offline methods can enhance the understanding of many human behaviours, but may be particularly useful in overcoming the difficulties inherent in criminological ethnography. For many (although by no means all) criminological topics, online methods can usefully enhance, but not replace, traditional ethnographic techniques.
‘Wearing down of the self’: Embodiment, writing and disruptions of identity in transformational festival fieldwork
Authors: Ruane Deirdre
Published: August 2017

Immersive ethnographic research can be profoundly destabilising for researchers’ sense of identity, and the attempt to inhabit and reconcile dual identities as researcher and participant can take a severe emotional toll. Prior to the reflexive turn in qualitative sociology, this identity work remained largely unacknowledged. Feminist critiques of positivist social science, along with personal accounts portraying the messy, chaotic aspects of research, have helped to create a new climate in which researchers can openly examine their identity conflicts and even recognise them as an integral part of their research. However, advice on navigating these situations remains somewhat limited. This article is a reflexive account of issues encountered while researching the practice of psychedelic support – the provision of emergency care to people undergoing drug-related crises – within the transformational festival scene in the United Kingdom, the United States and Portugal. Transformational festival settings are engineered to disrupt everyday experiences of identity and selfhood and induce emotional vulnerability. Thus, they throw issues of researcher identity and its management into sharp relief. Physically and emotionally intense fieldwork settings can bring about non-ordinary mental states in the researcher which can put habitual working practices and capacities out of reach. This effect contributed to a painful disjunction between my researcher and participant identities, which centred on the struggle to create linear, written narratives of largely embodied and non-verbal experiences. However, I found that the effect was somewhat mitigated by developing fluid, non-linear, multisensory working practices and documentation methods which were more appropriate to the research setting and the mental states it induced. I conclude that ethnographers in intense or extreme field settings can benefit greatly from methods and tools which work even when we are out of our everyday minds.
Mindfulness-based Intervention in Elementary School Students With Anxiety and Depression: A Series of n-of-1 Trials on Effects and Feasibility
Authors: Malboeuf-Hurtubise Catherine , Lacourse Eric , Herba Catherine , Taylor Geneviève , Amor Leila Ben
Published: August 2017

Mindfulness-based interventions constitute a promising option to address anxiety and depression in elementary school students. This study evaluated the effect of a mindfulness-based intervention on anxiety and depression in elementary school students with a diagnosis of anxiety or depression disorder. A single-subject experimental A-B-A design was used. Participants were three elementary school students from grades three and four, along with their teacher. Anxiety and depression were measured on 10 occasions at baseline, during the intervention, and at follow-up. Primary hypotheses were tested using a univariate single case multilevel modeling strategy and visual analysis. Following intervention, 2 participants reported improvements on anxiety and depression, while their teachers reported deteriorating scores on these variables. Results from this n-of-1 trial design is consistent with other work suggesting caution with regard to the overall impact and efficacy of mindfulness-based interventions as a universal treatment option for youth. Future research is warranted.
Pathological Personality Traits (DSM-5), Risk Factors, and Mental Health
Authors: Góngora Vanesa C. , Castro Solano Alejandro
Published: August 2017

This study aimed to evaluate the psychometric properties of the brief version of the Personality Inventory for DSM-5 (PID-5-BF) in a community sample of Argentine adult population, to establish its relationship with the Big Five normal personality traits, and to examine the association of pathological traits with mental and physical maladaptiveness assessed through the level of mental health and World Health Organization (WHO) health risk factors. The sample consisted of 1,032 subjects from the metropolitan area of Buenos Aires. The PID-5-BF, the Big Five Inventory, the Mental Health Continuum–Short Form, and the Survey on risk factors for noncommunicable diseases were used. A five-factorial structure that explained 59.48% of the variance was found, with reliability values higher than α = .86 for each factor. Convergences among pathological personality traits and the five-factor personality model were found, except for Psychoticism and Openness to experience. The severity of personality traits was associated with low levels of mental health and higher number of WHO health risk factors. Nevertheless, the associations among these variables were low to moderate.
Stress Response and Facial Trustworthiness Judgments in Civilians and Military
Authors: Toet Alexander , Bijlsma Martijn , Brouwer Anne-Marie
Published: August 2017

We tested the hypothesis that, either through training or selection, military personnel is more resilient to stress than civilians, as indicated by several subjective and physiological measures. In addition, we examined the effect of stress on the perceived trustworthiness of faces in these two groups. Stress was induced in 45 civilian participants and 45 army participants through the Sing-a-Song Stress Test (SSST). In this paradigm seven neutral sentences are presented, each followed by a 60-s interval. An eighth sentence asks participants to sing a song aloud after the next (eighth or stress) interval. Participants rated the trustworthiness of five neutral faces, both before and after the SSST. Pupil size, heart rate, and skin conductance were adopted as physiological stress correlates. Stress response was calculated as the difference between the mean values over the last neutral interval and the stress interval. Subjective stress ratings were obtained before and after the SSST. The baseline levels of all physiological and subjective measures were the same in the army and civilian groups, while all measures showed a significant increase following the stressor. However, compared with the civilian group, army participants reported significantly less stress and showed significantly attenuated heart rate and skin conductance responses to the SSST. These results indicate higher stress resilience in the army compared with the civilian group. In addition, we found that perceived facial trustworthiness decreased after presentation of the stressor, suggesting that the effect of a stressor can influence in principle unrelated social judgments based on facial information.
Perception of Facial Aging and Its Relationship to Two Single Nucleotide Polymorphisms (OXTR rs53576, CD38 rs3796863)
Authors: Gross Thomas J. , Gross Thomas F. , Blauth Susan
Published: August 2017

Oxytocin is associated with social behavior. In humans, several studies have assessed the relationship between social behavior and a single nucleotide polymorphism (SNP)—rs53576—within the gene encoding the oxytocin receptor (OXTR). Fewer studies have assessed the relationship between human sociability and the SNP rs3796863 found within the cluster of differentiation 38 (CD38) gene, whose product has been found to facilitate the secretion of oxytocin. This research examines whether these polymorphisms are associated with facial age discrimination. Young adults ( N = 43) were genotyped at both the OXTR and CD38 loci. They discriminated aging in 1- to 4-, 5- to 8-, 9- to 12-, 13- to 17-, and 18- to 22-year-old male and female faces. Participants with the OXTR GG and the CD38 CC genotypes discriminated facial aging better than those possessing at least one A allele at either locus. These polymorphisms appear to be associated with social information processing involved in facial age discrimination.
The Practice of Defect Liability Period in the Real Estate Industry in Ghana
Authors: Asante Lewis Abedi , Quansah Dennis Papa Odenyi , Ayitey Jonathan , Kuusaana Elias Danyi
Published: August 2017

A study on the dynamics of the defect liability period (DLP) in Ghana is lacking, notwithstanding the fact that it is a common practice in the real estate industry. This study examines the practice of the DLP in Ghana’s real estate industry. The study adopts a combination of simple random and stratified sampling techniques to select 29 members of the Ghana Real Estate Developers Association (GREDA) and 58 homeowners in Accra. We employ binary and multiple linear regression models to analyze the data gathered from the study respondents. Findings revealed that the DLP in Accra ranges from 6 to 24 months for defects to fittings and fixtures as well as to the structure. While private developers are divided on the adequacy of the DLP, homeowners believe that it is inadequate. Private developers suggest a longer DLP for the structure than for fittings and fixtures, whereas homeowners suggested longer DLP for both structure and fittings and fixtures. The implication of the findings is that longer DLP could be a strategy for attracting prospective homeowners. It is recommended, among others, that GREDA develop a manual to standardize the practice of the DLP in Ghana.
Efficacy of a computed tomography-based navigation system for placement of the acetabular component in total hip arthroplasty for developmental dysplasia of the hip
Authors: Tsutsui Takahiko , Goto Tomohiro , Wada Keizo , Takasago Tomoya , Hamada Daisuke , Sairyo Koichi
Published: August 2017

Purpose:

Developmental dysplasia of the hip (DDH) presents a considerable surgical challenge in total hip arthroplasty (THA). Although the usefulness of computed tomography (CT)-based navigation in cup alignment has been reported, few reports have evaluated three-dimensional (3-D) cup positioning against the acetabulum specifically in patients with DDH. The purpose of this study was to evaluate the efficacy of a CT-based navigation system for alignment and spatial positioning of the cup in THA for patients with DDH.

Methods:

We reviewed 174 DDH THA cases in which CT-based navigation was used, and 75 cases in which a mechanical guide was used as a control group. Postoperative cup alignment and spatial positioning were evaluated by superimposition of a 3-D cup template onto the actual implanted cup using postoperative CT images, with pelvic coordinates matching the preoperative planning.

Results:

The proportion within the combined target zone (inclination and anteversion) was 97.7% in the navigation group and 61.3% in the non-navigation group. The mean absolute error between the intraoperative record and the postoperative measurement was 1.5° ± 1.3° for inclination and 2.1° ± 1.8° for anteversion in the navigation group. For acetabular cup positioning, the mean discrepancy between the preoperative planning and the postoperative measurements was 1.9 ± 1.6 mm on the transverse axis, 2.8 ± 2.3 mm on the longitudinal axis, and 1.7 ± 1.3 mm on the sagittal axis.

Conclusion:

THA using a CT-based navigation system achieved quite high accuracy of cup alignment angles and spatial cup positioning in primary THA for patients with DDH.
An aberrant NOTCH2-BCR signaling axis in B cells from patients with chronic GVHD
Authors: Poe Jonathan C. , Jia Wei , Su Hsuan , Anand Sarah , Rose Jeremy J. , Tata Prasanthi V. , Suthers Amy N. , Jones Corbin D. , Kuan Pei Fen , Vincent Benjamin G. , Serody Jonathan S. , Horwitz Mitchell E. , Ho Vincent T. , Pavletic Steven Z. , Hakim Frances T. , Owzar Kouros , Zhang Dadong , Blazar Bruce R. , Siebel Christian W. , Chao Nelson J. , Maillard Ivan , Sarantopoulos Stefanie
Published: August 2017

Key Points

NOTCH2 activation confers a marked increase in BCR responsiveness by cGVHD patient B cells that associates with increased BLNK. ATRA increases the IRF4-to-IRF8 ratio and blocks aberrant NOTCH2-BCR activation without affecting cGVHD patient B-cell viability/function.
Preventing HIV infection without targeting the virus: how reducing HIV target cells at the genital tract is a new approach to HIV prevention
Authors: Lajoie Julie , Mwangi Lucy , Fowke Keith R.
Published: August 2017

For over three decades, HIV infection has had a tremendous impact on the lives of individuals and public health. Microbicides and vaccines studies have shown that immune activation at the genital tract is a risk factor for HIV infection. Furthermore, lower level of immune activation, or what we call immune quiescence, has been associated with a lower risk of HIV acquisition. This unique phenotype is observed in highly-exposed seronegative individuals from different populations including female sex workers from the Pumwani cohort in Nairobi, Kenya. Here, we review the link between immune activation and susceptibility to HIV infection. We also describe a new concept in prevention where, instead of targeting the virus, we modulate the host immune system to resist HIV infection. Mimicking the immune quiescence phenotype might become a new strategy in the toolbox of biomedical methods to prevent HIV infection.

Clinical trial registration on clinicaltrial.gov: #NCT02079077
The action of herbal medicine on the libido: aspects of nutritional intervention in increasing sexual desire
Authors: da Cruz Amanda Cássia , Guerra Natália Gonçalves , de Souza Kerolayne Esper Barão Pacelhe , de Castro Eleutério Izabella , da Silva Leidhaiane Custódia , Otoni Elaine Gomes , Alves Michelle Rosa Andrade , Regis Wiliam César Bento
Published: August 2017

Introduction

The libido is considered to be a sexual drive in individuals that can be determined and influenced by several factors, such as social, psychological, and hormonal factors. It is known that nutritional aspects are important hormone regulators and that sexual dysfunction may, in many cases, be reversed with simple lifestyle changes.

Aims

The aim of the study is to describe the actions of herbal medicine on the libido with an appropriate level of scientific evidence.

Methodology

A systematic review of the PUBMED, Scielo, and EMBASE databases was conducted, using the keywords “libido, food, and nutrient.”

Results

This study identified 2798 articles, 34 of which were selected, as they discussed exclusive studies involving herbal medicine. Some herbal medicines stood out, including Tribulus terrestris, used to increase testosterone serum levels; Eurycoma longifólia, which, in addition to the increased testosterone serum levels, also leads to an increased biosynthesis of several androgens; ginseng, which increases energy levels and stimulates smooth muscle relaxation with nitrous oxide; Maca (Lepidium meyenii), which improves sexual performance, in addition to having androgenic effects; and Mondia whitei (ginger), which improves the libido and erection. In addition to these, one study has demonstrated the effective impact of a hypocaloric, hyperproteic, and hypolipidemic diet on the libido, both improving sexual and erectile functions and increasing testosterone levels.

Conclusion

Herbal medicine analyzed in this study demonstrate positive effects on the libido, thus proving that, along with nutritional intervention, it is also a promising field in nutrition actions that provide support to combat sexual dysfunctions.
Toward Electronic Surveillance of Invasive Mold Diseases in Hematology-Oncology Patients: An Expert System Combining Natural Language Processing of Chest Computed Tomography Reports, Microbiology, and Antifungal Drug Data
Authors: Ananda-Rajah Michelle R. , Bergmeir Christoph , Petitjean François , Slavin Monica A. , Thursky Karin A. , Webb Geoffrey I.
Published: August 2017

Purpose

Prospective epidemiologic surveillance of invasive mold disease (IMD) in hematology patients is hampered by the absence of a reliable laboratory prompt. This study develops an expert system for electronic surveillance of IMD that combines probabilities using natural language processing (NLP) of computed tomography (CT) reports with microbiology and antifungal drug data to improve prediction of IMD.

Methods

Microbiology indicators and antifungal drug–dispensing data were extracted from hospital information systems at three tertiary hospitals for 123 hematology-oncology patients. Of this group, 64 case patients had 26 probable/proven IMD according to international definitions, and 59 patients were uninfected controls. Derived probabilities from NLP combined with medical expertise identified patients at high likelihood of IMD, with remaining patients processed by a machine-learning classifier trained on all available features.

Results

Compared with the baseline text classifier, the expert system that incorporated the best performing algorithm (naïve Bayes) improved specificity from 50.8% (95% CI, 37.5% to 64.1%) to 74.6% (95% CI, 61.6% to 85.0%), reducing false positives by 48% from 29 to 15; improved sensitivity slightly from 96.9% (95% CI, 89.2% to 99.6%) to 98.4% (95% CI, 91.6% to 100%); and improved receiver operating characteristic area from 73.9% (95% CI, 67.1% to 80.6%) to 92.8% (95% CI, 88% to 97.5%).

Conclusion

An expert system that uses multiple sources of data (CT reports, microbiology, antifungal drug dispensing) is a promising approach to continuous prospective surveillance of IMD in the hospital, and demonstrates reduced false notifications (positives) compared with NLP of CT reports alone. Our expert system could provide decision support for IMD surveillance, which is critical to antifungal stewardship and improving supportive care in cancer.
The Role of Sequential BMP Signaling in Directing Human Embryonic Stem Cells to Bipotential Gonadal Cells
Authors: Sepponen Kirsi , Lundin Karolina , Knuus Katri , Väyrynen Pia , Raivio Taneli , Tapanainen Juha S , Tuuri Timo
Published: August 2017

Context

Human gonads arise as a pair of epithelial ridges on the surface of intermediate mesoderm (IM)-derived mesonephros. Toxic environmental factors and mutations in various genes are known to disturb normal gonadal development, but because of a lack of suitable in vitro models, detailed studies characterizing the molecular basis of the observed defects have not been performed.

Objective

To establish an in vitro method for studying differentiation of bipotential gonadal progenitors by using human embryonic stem cells (hESCs) and to investigate the role of bone morphogenetic protein (BMP) in gonadal differentiation.

Design

We tested 17 protocols using activin A, CHIR-99021, and varying durations of BMP-7 and the BMP inhibitor dorsomorphin. Activation of activin A, WNT, and BMP pathways was optimized to induce differentiation.

Setting

Academic research laboratory.

Main Outcomes Measures

Cell differentiation, gene expression, and flow cytometry.

Results

The two most efficient protocols consistently upregulated IM markers LHX1, PAX2, and OSR1 at days 2 to 4 and bipotential gonadal markers EMX2, GATA4, WT1, and LHX9 at day 8 of culture. The outcome depended on the combination of the duration, concentration, and type of BMP activation and the length of WNT signaling. Adjusting any of the parameters substantially affected the requirements for other parameters.

Conclusions

We have established a reproducible protocol for directed differentiation of hESCs into bipotential gonadal cells. The protocol can be used to model early gonadal development in humans and allows further differentiation to mature gonadal somatic cells.
Smooth muscle cell recruitment to lymphatic vessels requires PDGFB and impacts vessel size but not identity
Authors: Wang Yixin , Jin Yi , Mäe Maarja Andaloussi , Zhang Yang , Ortsäter Henrik , Betsholtz Christer , Mäkinen Taija , Jakobsson Lars
Published: August 2017

Tissue-fluid drains through blind-ended lymphatic capillaries, via smooth muscle cell (SMC)-covered collecting vessels into venous circulation. Both defective SMC recruitment to collecting vessels and ectopic recruitment to lymphatic capillaries are thought to contribute to vessel failure, leading to lymphedema. However, mechanisms controlling lymphatic SMC recruitment and their role in vessel maturation are unknown. Here we demonstrate that platelet-derived growth factor B (PDGFB) regulates lymphatic SMC recruitment in multiple vascular beds. PDGFB is selectively expressed by lymphatic endothelial cells (LECs) of collecting vessels. LEC-specific deletion of Pdgfb prevented SMC recruitment causing dilation and failure of pulsatile contraction of collecting vessels. However, vessel remodelling and identity were unaffected. Unexpectedly, PDGFB overexpression in LECs did not induce SMC recruitment to capillaries. This was explained by the demonstrated requirement of PDGFB extracellular matrix (ECM) retention for lymphatic SMC recruitment, and low presence of PDGFB-binding ECM components around lymphatic capillaries. These results demonstrate a requirement of LEC-autonomous PDGFB expression and retention for SMC recruitment to lymphatic vessels and suggest an ECM-controlled checkpoint preventing SMC investment of capillaries, which is a common feature in lymphedematous skin.
miR-322 stabilizes MEK1 expression to inhibit RAF/MEK/ERK pathway activation in cartilage
Authors: Bluhm Björn , Ehlen Harald W. A. , Holzer Tatjana , Georgieva Veronika S. , Heilig Juliane , Pitzler Lena , Etich Julia , Bortecen Toman , Frie Christian , Probst Kristina , Niehoff Anja , Belluoccio Daniele , Van den Bergen Jocelyn , Brachvogel Bent
Published: August 2017

Cartilage originates from mesenchymal cell condensations that differentiate into chondrocytes of transient growth plate cartilage or permanent cartilage of the articular joint surface and trachea. MicroRNAs fine-tune the activation of entire signaling networks and thereby modulate complex cellular responses, but so far only limited data are available on miRNAs that regulate cartilage development.

Here we characterize a miRNA which promotes the biosynthesis of a key component in the RAF/MEK/ERK pathway in cartilage. Specifically, by transcriptome profiling we identified miR-322 to be upregulated during chondrocyte differentiation. Among the various miR-322 target genes in the RAF/MEK/ERK pathway only Mek1 was identified as a regulated target in chondrocytes. Surprisingly, an increased concentration of miR-322 stabilizes Mek1-mRNA to rise protein levels and dampen ERK1/2 phosphorylation, while cartilage-specific inactivation in mice linked the loss of miR-322 to decreased MEK1 levels and increased RAF/MEK/ERK pathway activation. Such mice died perinatally due to tracheal growth restriction and respiratory failure.

Hence, a single miRNA can stimulate the production of an inhibitory component of a central signaling pathway to impair cartilage development.
Imp and Syp RNA-binding proteins govern decommissioning ofDrosophilaneural stem cells
Authors: Yang Ching-Po , Samuels Tamsin J. , Huang Yaling , Yang Lu , Ish-Horowicz David , Davis Ilan , Lee Tzumin
Published: August 2017

The termination of the proliferation of Drosophila neural stem cells, also known as neuroblasts (NBs), requires a “decommissioning” phase that is controlled in a lineage-specific manner. Most NBs, with the exception of those of the Mushroom body (MB), are decommissioned by the ecdysone receptor and mediator complex causing them to shrink during metamorphosis, followed by nuclear accumulation of Prospero and cell cycle exit. Here, we demonstrate that the levels of Imp and Syp RNA-binding proteins regulate NB decommissioning. Descending Imp and ascending Syp expression have been shown to regulate neuronal temporal fate. We show that Imp levels decline slower in the MB than other central brain NBs. MB NBs continue to express Imp into pupation, and the presence of Imp prevents decommissioning partly by inhibiting the mediator complex. Late-larval induction of transgenic Imp prevents many non-MB NBs from decommissioning in early pupae. Moreover, the presence of abundant Syp in aged NBs permits Prospero accumulation that, in turn, promotes cell cycle exit. Together our results reveal that progeny temporal fate and progenitor decommissioning are co-regulated in protracted neuronal lineages.
Psychrophilic proteases dramatically reduce single cell RNA-seq artifacts: A molecular atlas of kidney development
Authors: Adam Mike , Potter Andrew S. , Potter S. Steven
Published: August 2017

Single cell RNA-seq is a powerful methodology. Nevertheless there are important limitations, including the technical challenges of breaking down an organ or tissue into a single cell suspension. Invariably this has required enzymatic incubation at 37°C, which can be expected to result in artifact changes in gene expression patterns. We here describe a dissociation method that uses a protease with high activity in the cold, purified from a psychrophilic microorganism. The entire procedure is carried out at 6°C or colder, where mammalian transcriptional machinery is largely inactive, thereby effectively “freezing in” the in vivo gene expression patterns. To test this method we carried out RNA-seq on 20,424 single cells from P1 mouse kidneys, comparing the results of the psychrophilic protease method with procedures using 37°C incubation. We show that the cold protease method provides a great reduction in gene expression artifacts. In addition the results produce a single cell resolution gene expression atlas of the newborn mouse kidney, an interesting time in development when mature nephrons are present yet nephrogenesis remains extremely active.
Notch signaling patterns neurogenic ectoderm and regulates the asymmetric division of neural progenitors in sea urchin embryos
Authors: Mellott Dan O. , Thisdelle Jordan , Burke Robert D.
Published: August 2017

We have examined regulation of neurogenesis by Delta/Notch signaling in sea urchin embryos. At gastrulation neural progenitors enter S-phase coincident with expression of Sp-SoxC. We used a BAC (bacterial artificial chromosome) containing GFP knocked into the Sp-SoxC locus to label neural progenitors. Live imaging and immunolocalizations indicate that Sp-SoxC-expressing cells divide producing pairs of adjacent cells expressing GFP. Over an interval of about 6 h, one cell fragments, undergoes apoptosis, and expresses high levels of activated Caspase3. A Notch reporter indicates that Notch signaling is activated in cells adjacent to cells expressing Sp-SoxC. Inhibition of γ-secretase, injection of Sp-Delta morpholinos, or CRISPR/Cas9-induced mutation of Sp-Delta results in supernumerary neural progenitors and neurons. Interfering with Notch signaling increases neural progenitor recruitment and pairs of neural progenitors. Thus, Notch signaling restricts the number of neural progenitors recruited and regulates the fate of progeny of the asymmetric division. We propose a model in which localized signaling converts ectodermal and ciliary band cells to neural progenitors that divide asymmetrically to produce a neural precursor and an apoptotic cell.
DNA damage induces a kinetochore-based ATM/ATR-independent SAC arrest unique to the first meiotic division in mouse oocytes
Authors: Lane Simon I. R. , Morgan Stephanie L. , Wu Tianyu , Collins Josie K. , Merriman Julie A. , ElInati Elias , Turner James M. , Jones Keith T.
Published: August 2017

Mouse oocytes carrying DNA damage arrest in meiosis I, thereby preventing creation of embryos with deleterious mutations. The arrest is dependent on the spindle assembly checkpoint, which results in anaphase-promoting complex (APC) inhibition. However, little is understood about how this checkpoint is engaged following DNA damage. Here, we find that within minutes DNA damage assembles checkpoint proteins at the kinetochore, not at damage sites along chromosome arms, such that the APC is fully inhibited within 30 min. Despite this robust response, there is no measurable loss in k-fibres, or tension across the bivalent. Through pharmacological inhibition we observed the response is dependent on Mps1 kinase, Aurora kinase, and haspin. Using oocyte specific knockouts we find the response does not require the DNA damage response kinases ATM or ATR. Furthermore, checkpoint activation does not occur in response to DNA damage in fully mature eggs during meiosis II, despite the divisions being separated by just a few hours. Therefore, mouse oocytes have a unique ability to sense DNA damage rapidly by activating the checkpoint at their kinetochores.
Perturbing phosphoinositide homeostasis oppositely affects vascular differentiation in Arabidopsis thaliana roots
Authors: Gujas Bojan , Cruz Tiago M. D. , Kastanaki Elizabeth , Vermeer Joop E. M. , Munnik Teun , Rodriguez-Villalon Antia
Published: August 2017

The plant vascular network consists of specialized phloem and xylem elements that undergo two distinct morphogenetic developmental programs to become transport-functional units. While vacuolar rupture is a determinant step in protoxylem differentiation, protophloem elements never form a big central vacuole. Here we show that a genetic disturbance of phosphatidylinositol 4,5-bis-phosphate [PtdIns(4,5)P2] homeostasis rewires cell trafficking towards the vacuole in Arabidopsis thaliana roots. Consequently, an enhanced phosphoinositide-mediated vacuolar biogenesis correlate with premature programmed cell death (PCD) and secondary cell wall elaboration in xylem cells. By contrast, vacuolar fusion events in protophloem cells trigger the abnormal formation of big vacuoles, preventing cell clearance and tissue functionality. Removal of the inositol 5’ phosphatase COTYLEDON VASCULAR PATTERN2 from the plasma membrane (PM) by brefeldin A (BFA) treatment increases PtdIns(4,5)P2 content at the PM and disrupts protophloem continuity. Conversely, BFA application abolishes vacuolar fusion events in xylem tissue without preventing PCD, suggesting the existence of additional PtdIns(4,5)P2–dependent cell death mechanisms. Overall, our data indicate that a tight PM phosphoinositide homeostasis is required to modulate intracellular trafficking contributing to oppositely regulate vascular differentiation.
Considering aspects of the 3Rs principles within experimental animal biology
Authors: Sneddon Lynne U. , Halsey Lewis G. , Bury Nic R.
Published: August 2017

The 3Rs – Replacement, Reduction and Refinement – are embedded into the legislation and guidelines governing the ethics of animal use in experiments. Here, we consider the advantages of adopting key aspects of the 3Rs into experimental biology, represented mainly by the fields of animal behaviour, neurobiology, physiology, toxicology and biomechanics. Replacing protected animals with less sentient forms or species, cells, tissues or computer modelling approaches has been broadly successful. However, many studies investigate specific models that exhibit a particular adaptation, or a species that is a target for conservation, such that their replacement is inappropriate. Regardless of the species used, refining procedures to ensure the health and well-being of animals prior to and during experiments is crucial for the integrity of the results and legitimacy of the science. Although the concepts of health and welfare are developed for model organisms, relatively little is known regarding non-traditional species that may be more ecologically relevant. Studies should reduce the number of experimental animals by employing the minimum suitable sample size. This is often calculated using power analyses, which is associated with making statistical inferences based on the P-value, yet P-values often leave scientists on shaky ground. We endorse focusing on effect sizes accompanied by confidence intervals as a more appropriate means of interpreting data; in turn, sample size could be calculated based on effect size precision. Ultimately, the appropriate employment of the 3Rs principles in experimental biology empowers scientists in justifying their research, and results in higher-quality science.
The thermal background determines how the infrared and visual systems interact in pit vipers
Authors: Chen Qin , Liu Yang , Brauth Steven E. , Fang Guangzhan , Tang Yezhong
Published: August 2017

The thermal infrared (IR) sensing system of pit vipers is believed to complement vision and provide a substitute imaging system in dark environments. Theoretically, the IR system would best image a scene consisting of a homothermal target in cold surroundings as a bright spot on a dark background. To test this hypothesis, we evaluated how the pit viper (Gloydius brevicaudus) discriminates and strikes prey when the background temperature is either higher or lower than that of the prey (approximately 32–33°C) in different parts of the scene. Snakes were tested in a modified predation cage in which background temperatures were set to 26°C on one side and either 33 or 40°C on the opposite side when the eyes, the pit organs or neither sensory system was occluded. When the eyes were blocked, snakes preferred to strike prey on the 26°C side rather than on the 33°C side but showed no bias in the other conditions. Snakes showed no preference for 26 versus 40°C background temperature, although more missed strikes occurred when the eyes were occluded. The results thus revealed that the pit viper IR system can accomplish a ‘brightness constancy’ computation reflecting the difference between the target and background temperatures, much as the visual system compares the luminance of a figure and the background. Furthermore, the results show that the IR system performs less well for locating prey when the background is warmer than the target.
Pharmacological effects of cannabinoids on learning and memory in Lymnaea
Authors: Sunada Hiroshi , Watanabe Takayuki , Hatakeyama Dai , Lee Sangmin , Forest Jeremy , Sakakibara Manabu , Ito Etsuro , Lukowiak Ken
Published: August 2017

Cannabinoids are hypothesized to play an important role in modulating learning and memory formation. Here, we identified mRNAs expressed in Lymnaea stagnalis central nervous system that encode two G-protein-coupled receptors (Lymnaea CBr-like 1 and 2) that structurally resemble mammalian cannabinoid receptors (CBrs). We found that injection of a mammalian CBr agonist WIN 55,212-2 (WIN 55) into the snail before operant conditioning obstructed learning and memory formation. This effect of WIN 55 injection persisted for at least 4 days following its injection. A similar obstruction of learning and memory occurred when a severe traumatic stimulus was delivered to L. stagnalis. In contrast, injection of a mammalian CBr antagonist AM 251 enhanced long-term memory formation in snails and reduced the duration of the effects of the severe traumatic stressor on learning and memory. Neither WIN 55 nor AM 251 altered normal homeostatic aerial respiratory behaviour elicited in hypoxic conditions. Our results suggest that putative cannabinoid receptors mediate stressful stimuli that alter learning and memory formation in Lymnaea. This is also the first demonstration that putative CBrs are present in Lymnaea and play a key role in learning and memory formation.
O2 binding and CO2 sensitivity in hemoglobins of subterranean African mole rats
Authors: Weber Roy E. , Jarvis Jennifer U. M. , Fago Angela , Bennett Nigel C.
Published: August 2017

Inhabiting deep and sealed subterranean burrows, mole rats exhibit a remarkable suite of specializations, including eusociality (living in colonies with single breeding queens), extraordinary longevity, cancer immunity and poikilothermy, and extreme tolerance of hypoxia and hypercapnia.With little information available on adjustments in hemoglobin (Hb) function that may mitigate the impact of exogenous and endogenous constraints on the uptake and internal transport of O2, we measured hematological characteristics, as well as Hb-O2 binding affinities and their sensitivities to pH (Bohr effect), CO2, temperature and 2,3 diphosphoglycerate (DPG, the major allosteric modulator of Hb-O2 affinity in the red cells) in four social and two solitary species of African mole rats (family Bathyergidae) originating from different biomes and soil types across Central and Southern Africa. We find no consistent patterns in hematocrit (Hct) and blood and red cell DPG and Hb concentrations or in intrinsic Hb-O2 affinity and its sensitivity to pH and DPG that correlate with burrowing, sociality and soil-type. However, the results reveal low specific (pH-independent) effects of CO2 on Hb-O2 affinity compared to humans that predictably safeguard pulmonary loading under hypoxic and hypercapnic burrow conditions. The O2-binding characteristics are discussed in relation to available information on the primary structure of Hbs from adult and developmental stages of mammals subjected to hypoxia and hypercapnia and the molecular mechanisms underlying functional variation in rodent Hbs.
Exercise Is an Adjuvant to Contemporary Dystrophy Treatments
Authors: Kostek Matthew C. , Gordon Bradley
Published: August 2017

Duchenne muscular dystrophy is a lethal genetic disease of muscle wasting for which there is no cure. In healthy muscle, structure and function improve dramatically with exercise. In patients with dystrophy, little is known about the effects of exercise. As contemporary therapies rapidly progress and patients become more active, there is a need to understand the effects of exercise.
The Vehicle Routing Problem with Release and Due Dates
Authors: Shelbourne Benjamin C. , Battarra Maria , Potts Chris N.
Published: August 2017

A novel extension of the classical vehicle routing and scheduling problems is introduced that integrates aspects of machine scheduling into vehicle routing. Associated with each customer order is a release date that defines the earliest time that the order is available to leave the depot for delivery and a due date that indicates the time by which the order should ideally be delivered to the customer. The objective is to minimize a convex combination of the operational costs and customer service level, represented by the total distance traveled and the total weighted tardiness of delivery, respectively. A path-relinking algorithm (PRA) is proposed to address the problem, and a variety of benchmark instances are generated to evaluate its performance. The PRA exploits the efficiency and aggressive improvement of neighborhood search but relies on a new path-relinking procedure and advanced population management strategies to navigate the search space effectively. To provide a comparator algorithm to the PRA, we embed the neighborhood search into a standard iterated local search algorithm (ILS). Extensive computational experiments on the benchmark instances show that the newly defined features have a significant and varied impact on the problem, and the performance of the PRA dominates that of the ILS algorithm.

The online supplement is available at https://doi.org/10.1287/ijoc.2017.0756 .
Investigating the Spillover Effect of Keyword Market Entry in Sponsored Search Advertising
Authors: Lu Shijie , Yang Sha
Published: August 2017

As Internet advertising infomediaries nowadays provide rich competition information, sponsored search advertisers are becoming more strategic when selecting keywords. This paper empirically examines the spillover effects in advertisers’ keyword market entry decisions, that is, how an advertiser’s likelihood of using a keyword is affected by competitors’ keyword entry decisions. We develop a structural model to characterize advertisers’ keyword market entry decisions. We apply the model to a panel data set of 1,252 laptop-related keywords mainly used by 28 manufacturers, retailers, and comparison websites that advertise on Google. Our analysis leads to several interesting findings. First, an advertiser’s expected position affects the nature of the competition. In particular, the spillover effect from below-ranked competitors is always positive, while the spillover effect from above-ranked competitors is either positive or negative. Second, the spillover effect from above-ranked ads is directionally affected by firms’ product-line characteristics: the effect among firms offering homogenous products (e.g., comparison sites) is negative, whereas the effect among firms with more differentiated products (e.g., manufacturers and retailers) is positive. Third, the spillover effect from above-ranked ads is directionally affected by firms’ positions in a distribution channel: the effect from upstream (downstream) on downstream (upstream) firms tends to be negative (positive). Finally, a downstream firm is more likely to learn new keywords from an upstream firm but not vice versa. Our counterfactual simulations demonstrate that the keyword-specific competition information provided by infomediaries can improve the search engine’s revenue by about 5.7%.

Data are available at https://doi.org/10.1287/mksc.2017.1053 .
Discretionary Task Ordering: Queue Management in Radiological Services
Authors: Ibanez Maria R. , Clark Jonathan R. , Huckman Robert S. , Staats Bradley R.
Published: August 2017

Work scheduling research typically prescribes task sequences implemented by managers. Yet employees often have discretion to deviate from their prescribed sequence. Using data from 2.4 million radiological diagnoses, we find that doctors prioritize similar tasks (batching) and those tasks they expect to complete faster (shortest expected processing time). Moreover, they exercise more discretion as they accumulate experience. Exploiting random assignment of tasks to doctors’ queues, instrumental variable models reveal that these deviations erode productivity. This productivity decline lessens as doctors learn from experience. Prioritizing the shortest tasks is particularly detrimental to productivity. Actively grouping similar tasks also reduces productivity, in stark contrast to productivity gains from exogenous grouping, indicating deviation costs outweigh benefits from repetition. By analyzing task completion times, our work highlights the trade-offs between the time required to exercise discretion and the potential gains from doing so, which has implications for how discretion over scheduling should be delegated.

The online appendix is available at https://doi.org/10.1287/mnsc.2017.2810 .

This paper was accepted by Serguei Netessine, operations management.
Uncertainty, Capital Investment, and Risk Management
Authors: Doshi Hitesh , Kumar Praveen , Yerramilli Vijay
Published: August 2017

We use forward-looking and exogenous measures of output price uncertainty to examine the effect of price uncertainty on firm-level capital investment, risk management, and debt issuance. The effects of uncertainty vary significantly by firm size. When faced with high price uncertainty, large firms increase their hedging intensity but do not lower capital investment or debt issuance. In contrast, small firms do not adjust their hedging intensity but significantly lower capital expenditure and debt issuance even after controlling for investment demand. Moreover, the negative effect of uncertainty on capital investment is significantly weaker for firms that hedge their output price risk. Our analysis highlights that, in the presence of financial frictions, high price uncertainty has significant dampening effects on capital investment of small firms by exacerbating their financial constraints, and that this negative effect is amplified by firm-level constraints on ability to hedge risk exposures.

The Internet appendix is available at https://doi.org/10.1287/mnsc.2017.2815 .

This paper was accepted by Amit Seru, finance.
Research roundup
Authors: Costello John
Published: August 2017

Synopses of a selection of recently published research articles of relevance to palliative care.
Politics and palliative care: Togo
Authors: Smyth Dion
Published: August 2017

Dion Smyth's review of palliative nursing on the internet
Incidental finding of a persistent median artery (palmar type) during a routine carpal tunnel decompression: a case report
Authors: Butt J , Ahluwalia AK , Dutta A
Published: August 2017

Carpal tunnel syndrome is characterised by compression of the median nerve. The mainstay of treatment is surgical decompression. This case report highlights the occurrence of a persistent median artery, which could complicate surgery. A 55-year-old woman underwent carpal tunnel decompression. An incidental finding of a large-calibre persistent median artery, which was superficial to the flexor sheath, could have been damaged. This was carefully retracted and the procedure was completed, without any complications. Several studies have shown the prevalence of persistent median artery to range from 1.1–27.1%. It is usually found deep to the flexor retinaculum but in this case it was found to be just beneath the palmar fascia. There is increased chance of iatrogenic injury with this particular variant. Surgeons performing the procedure should be mindful of this variation, because accidental damage could result in devastating consequences to the hand.