bluuebunny/crossref_metadata_2025 huggingface dataset:
A diachronic take on the Source–Goal asymmetry
Authors: Georgakopoulos Thanasis , Karatsareas Petros
Published: August 2017

A bulk of typological and crosslinguistic evidence on the internal structure of motion events has shown that Goals and Sources behave asymmetrically. This asymmetry exhibits several morphosyntactic and semantic realizations: Goal markers are morphologically simpler than Source markers; there tend to be more fine-grained semantic distinctions within the Goal domain than within the Source domain, leading to higher numbers of markers for the encoding of Goal than of Source (type level); Goals are more frequently zero-marked than Sources; and, Goal relations are encoded more frequently in discourse (token level). In this chapter, we report similar imbalances in the behavior of Sources and Goals in inner Asia Minor Greek. We find that Goal markers are more numerous than markers denoting Source and that Goal paths are more often explicitly expressed in discourse. Additionally, we test the diachronic validity of these findings, which have been reached on the basis of mostly synchronic investigations, by examining the historical developments that the Modern Greek dialects of inner Asia Minor underwent in the formal expression of Goal and Source. We analyze the (a)symmetrical relations that hold between the two locative roles as evidenced by the qualitative and quantitative use of the prepositions se ‘to, at’, os ‘up to, until’, tʃax/tʃáus ‘up to, until’, and apó ‘from’, focusing specifically on the implications that the diachronic loss of se, the most frequent Goal marker, had for the spatial system of inner Asia Minor Greek. Our analysis shows that overt Goal markers remain morphologically less complex than Source markers across diachronic stages; and, that the Goal marker develops into a zero marker earlier than the Source marker. These findings support the Goal-over-Source predominance hypothesis. However, our analysis also indicates that the asymmetry could under certain circumstances work in the opposite direction.
Asymmetries in path encoding in Sicilian
Authors: Brucale Luisa , Mocciaro Egle
Published: August 2017

This paper proposes a description of the encoding of path within the system of the spatial relations in present-day Sicilian, with a retrospective glance to the diachronic developments of that system. Two features characterize the spatial relations in present-day Sicilian: (a) consistent with a cross-linguistic tendency, the relation between source and direction is asymmetric, as the latter receives a richer and more fine-grained expression; moreover, direction may conflate into locative expression; (b) in contrast with a cross-linguistic tendency, which predicts a lower degree of autonomy for path, this role has a dedicated preposition and makes use of a non-prepositional strategy, namely a reduplicative construction expressing the spatial extension through which the event is brought about. The diachronic development of present-day system has been reconstructed by means of the scrutiny of corpus data from 14th to 19th centuries. This analysis has shown a substantial consistency in the encoding of spatial relations over time, although a certain degree of variation of the linguistic means expressing them.
Prepositional phrase vs. bare instrumental
Authors: Philippova Natalia
Published: August 2017

The trajectory of motion in Russian can be expressed by a prepositional phrase with the noun in the dative case or a bare NP in the instrumental case. It is argued that the latter construction is falling into disuse, along with the general trend toward analyticity in Slavic languages (Comrie et al. 1996). In this paper, I present a corpus-based diachronic study of the distribution of the two constructions with respect to various variables, such as noun frequency, the conceptualization of the Ground object, verb aspect, and others. I provide an argument that the bare NP construction is going through lexicalization as an adverb.
In the face of resistance
Authors: Etelämäki Marja , Couper-Kuhlen Elizabeth
Published: August 2017

In this paper we focus on one particular practice for dealing with resistance to an imperatively formatted directive, namely that of re-issuing the directive in a second-person declarative form as a subsequent version. In our data, from Finnish everyday adult interaction, this practice is used either after straightforward resistance or after lack of full commitment to the directive. In the former case, the subsequent version insists on the directive by disregarding the resistance and any accounts given for it. In the latter case, the subsequent version insists on the directive not by merely reiterating it but by dealing with possible obstacles that might prevent the recipient from committing to it. We argue that the second-person declarative form of the subsequent version is understood deontically because the prior imperative form has set up a directive context. Moreover, the declarative form makes explicit a “you – me” axis and treats the intended action, which the recipient is to carry out, as a fait accompli. Whereas imperative forms, lacking person marking, put a focus on the action, declarative forms, with person marking, foreground the participants’ relationship to one another when these forms follow resistance. The use of this practice confirms the earlier claim made about imperatives, namely that they expect immediate commitment, since if imperatively formatted directives are resisted, the imperative form is not repeated as such in the subsequent version.
Managing compliance in violin instruction
Authors: Stevanovic Melisa
Published: August 2017

The chapter considers the verbal design of Finnish second-person singular imperative and first-person plural hortative turns, asking whether and how those turns where there is a clitic particle -pA or -pAs attached to the finite verb differ from the non-cliticized turns, and whether -pA and -pAs are used in similar or dissimilar ways. The imperative and hortative turns used in the analysis are drawn from a data set of four violin lessons with a 5-year-old child and her teacher as the participants. All the imperative and hortative turns analyzed were spoken by the teacher to the child.

The analysis shows that the non-cliticized imperative or hortative turns and the ones with -pA or -pAs are used differently. The non-cliticized turns are common in contexts where the speaker and the recipient are actively engaged in an ongoing collaboration. The imperative and hortative turns with ‑pA occur characteristically after the recipient’s immediately preceding failures, which need to be remedied for the participants to be able to continue what they are up to. The imperatives and hortatives with ‑pAs are frequently used at activity transitions, where the speaker demonstrates her right to determine the broader agenda of the participants’ joint activity.

The chapter suggests that the linguistic design of Finnish second-person singular imperative and first-person plural hortative turns is informed by the speaker’s understanding of the extent to which, and the particular sense in which, the participants’ current actions are to be seen as joint ones. While the selection between imperatives and hortatives is warranted by the identity of the agent(s) of the nominated action (whether it is the recipient alone, or both the speaker and the recipient together), it is in and through the choices between the cliticized and non-cliticized formats that speakers invoke and manage the more specific basis upon which the recipient’s compliance can be expected.
Adjusting the design of directives to the activity environment
Authors: Raevaara Liisa
Published: August 2017

This chapter examines the design of directives in Finnish conversation in the specific institutional setting of cooking club meetings held in a youth club. During these meetings, children bake pastries and a teacher supervises them, organising activities and giving the children instructions and advice. This chapter focuses on the teacher’s verbal directives. More specifically, the analysis examines imperatively formatted directives, but also compares the activity environments in which imperatives and other directive formats are used, especially second-person declaratives. This choice of these different formats is discussed as well as the specific design features of the imperatively formatted turns, exploring how they are adjusted to the progress and temporality of the ongoing actions as well as to the emerging participation framework.
Climatic limiting factors: temperature.
Authors: Wenden B. , Campoy J. A. , Jensen M. , López-Ortega G.
Published: August 2017

This chapter focuses on the effect of temperature on seed dormancy, cold resistance and spring frost damage in cherries and effects of warm temperatures on flower and fruit development. The consequences of global warming on the survival and production of cherries are also discussed.
Orchard microclimate modification.
Authors: Blanke M. M. , Lang G. A. , Meland M.
Published: August 2017

This chapter focuses on the effects of light, temperature, wind speed and relative humidity in determining the extent to which cherry can be grown in a particular environment. The importance of microclimate modification in cherry production, such as the use of orchard covers, and its effects on plant development, fruit production, pests and diseases and fruit quality are also discussed.
Viruses, viroids, phytoplasmas and genetic disorders of cherry.
Authors: James D. , Cieślińska M. , Pallás V. , Flores R. , Candresse T. , Jelkmann W.
Published: August 2017

This chapter focuses on some of the most important viruses, viroids and phytoplasmas affecting cherries. The efficacy of some methods used in the control of these pathogens and their vectors are discussed. Some cherry disorders attributed to genetic abnormalities are also presented.
Sample Size Estimation for On-Site Creel Surveys
Authors: McCormick Joshua L. , Meyer Kevin A.
Published: August 2017

Conducting sample size analysis is important to ensure that sample sizes are adequate to meet objectives for precision but not so large that valuable resources are wasted. When simple survey designs are used, sample size analysis is straightforward. However, creel surveys often follow complex designs that can make sample size estimation difficult. The objectives of this study were to provide sample size estimators for commonly used creel survey designs and investigate sample size requirements to achieve varying levels of precision. For estimates of angling effort, the average sample size among fisheries required to achieve relative 95% confidence intervals of 40% (i.e., coefficient of variation of approximately 0.2) was 16 d (range = 7–40 d). To estimate mean catch rate with the same level of precision, 43 survey days (range = 8–95 d) were required when the daily catch rate estimator was used, and 11 d (range = 3–30 d) were required when the multi-day estimator was used. Fifty-five days (range = 14–89 d) and 57 d (range = 19–140 d) were required to estimate total catch with relative 95% confidence intervals of 40% when the daily and multi-day estimators were used, respectively. Although absolute precision will vary among fisheries, our results suggest that approximately 30 d of surveying may serve as a reasonable starting point for planning creel surveys when no prior information is available on expected sample variance, as relatively large increases in sample size beyond 30 d were needed to achieve relatively small increases in precision.

Received February 14, 2017; accepted June 9, 2017 Published online August 4, 2017
Do advanced glycation end-products cause food allergy?
Authors: Smith Peter K.
Published: August 2017

Purpose of review

The aim of this study was to appraise the evidence relating to dietary advanced glycation end-products (AGEs), their influence on innate and adaptive immune responses and their possible role in the increasing rate of food allergy that is being observed globally.

Recent findings

The western pattern of diet is high in both AGEs and their substrates and this has been increasing in the last 30 years. AGEs mimic alarmins such as S100 proteins and the high molecular group box 1 (HMBG1), binding to the Receptor for Advanced Glycation End Products (RAGE), which in turn influences innate and adaptive immune responses. AGEs can directly cause mast cell activation and degranulation. Population data from USA and Australia have correlates with the rise in food allergy and sources of AGEs in the diet and this is also reinforced by urban and regional data within countries. The function of the RAGE receptor is inter-twined with Toll-like receptor (TLR) signalling and vitamin D levels. Activation of the RAGE receptor results in loss of epithelial integrity. Animal models studies have shown that dietary compounds that reduce the formation of AGEs can protect from the development of food allergies; however, this has not been shown in humans.

Dietary sources of AGEs and their substrates are a plausible contributor to the increasing prevalence of food allergy, which requires prospective evaluation in human populations.
Deep Transverse Metacarpal Ligament Reconstruction Using Suture Button and A1 Pulley
Authors: Piercey Joshua , McEniery Paul , Green Nicholas
Published: August 2017

Rupture of the deep transverse metacarpal ligament (DTML) can result in pain, impaired grip strength, and undermine functional performance of the hand. We describe the case of a patient whose right hand came into contact with a boat propeller. He sustained a complete disruption of the DTML between the second and third ray in addition to soft tissue injury and open metacarpal fractures. Although other techniques describe a reconstruction of the DTML, our technique describes an adjunctive technique that strongly augments the A1 pulley reconstruction and nullifies the requirements of palmaris longus graft.
Examining the impact of succession management practices on organizational performance: A national study of U.S. hospitals
Authors: Groves Kevin S.
Published: August 2017

Background:

Spearheaded by the industry's transition from volume- to value-based care, the health care reform movement has spurred both unprecedented challenges and opportunities for developing more effective and sustainable health care delivery organizations. Whereas the formidable challenges of leading hospitals and health systems have been widely discussed, including reimbursement degradation, the rapidly aging workforce, and the imminent wave of executive retirements, the opportunity to leverage succession management and talent development capabilities to overcome these challenges has been largely overlooked.

Purpose:

To address this key research and practice need, this multiphase study develops and validates an assessment of succession management practices for health care organizations.

Methodology:

Utilizing data collected from two national samples of hospital organizations, the results provide a 32-item succession management assessment comprising seven distinct sets of succession management practices.

Results:

The results indicate that succession management practices are strongly associated with multiple hospital performance metrics, including patient satisfaction and Medicare Spending per Beneficiary, leadership bench strength, and internal/external placement rate for executive level positions.

Practice Implications:

The author concludes this article with a discussion of several practical implications for health care executives and boards, including employing the succession management assessment for diagnosing development opportunities, benchmarking succession planning and talent development practices against similar hospitals or health systems, and elevating the profile of succession management as a strategic priority in today's increasingly uncertain health care landscape.
Flow in Nurses
Authors: Martínez-Zaragoza Fermín , Benavides-Gil Gemma , Martín-del-Río Beatriz , Fernández-Castro Jordi , Ato-García Manuel , Solanes-Puchol Ángel
Published: August 2017

How does the experience of flow among nurses influences their health? This question is addressed on the basis of a model of flow, stress, burnout, and coping. The results indicate that promoting flow can be a way to enhance the health of ward nurses in a hospital work context.
Complementary Health Approaches Used in the Intensive Care Unit
Authors: Erdoğan Zeynep , Atik Derya
Published: August 2017

Intensive care units are care centers where, in order to provide the maximum benefit to individuals whose life is in danger, many lifesaving technological tools and devices are present, and morbidity and mortality rates are high. In the intensive care unit, when classic treatments fail or become unbearable because of side effects, complementary methods have been suggested to be the best alternative. Complementary health approaches are methods that are used both for the continuation and the improvement of the well-being of an individual and as additions to medical treatments that are based on a holistic approach. These applications are especially helpful in the treatment of the stresses, anxieties, and other symptoms of unstable patients in the intensive care unit who do not tolerate traditional treatment methods well, increasing their psychological and physiological well-being, helping them sleep and rest. In intensive care patients, in order to decrease the incidence of postoperative atrial fibrillation, antiemetic and medicine needs, mechanical ventilation duration, and the intensity of the disease as well as to cope with symptoms such as pain, anxiety, physiological parameters, dyspnea, and sleep problems, body-mind interventions such as massage, reflexology, acupressure, aromatherapy, music therapy, energy therapies (healing touch, therapeutic touch, the Yakson method), and prayer are used as complementary health approaches.
Hospital Readmission From the Perspective of Medicaid and Uninsured Patients
Authors: Misky Gregory J. , Burke Robert E. , Johnson Teresa , del Pino Jones Amira , Hanson Janice L. , Reid Mark B.
Published: August 2017

Background:

Patients with little or no health insurance are frequently readmitted to the hospital, yet few previous studies have listened to patients' explanations of why they returned to the hospital after discharge. Enhanced understanding of patient perspectives may facilitate targeted services and improve care.

Methods:

We enrolled 18 patients with Medicaid or no insurance during a hospital readmission within 30 days in a major metropolitan area, and conducted semi-structured qualitative interviews to explore the impact of patients' experiences around readmission using a grounded theory approach.

Results:

We identified five themes contributing to readmission: (1) therapeutic misalignment; (2) accountability; (3) social fragility; (4) access failures; and (5) disease behavior. Medical conditions were complicated by social influences and insufficiently addressed by our health system. Patients understood the need to manage their own health but were unable to effectively execute care plans because of competing life demands and compromised relationships with health providers.

Conclusions:

Our study using interviews of readmitted Medicaid and uninsured patients revealed complex illnesses complicated by social instability and health system failures. Improved patient-provider trust and shared decision-making, while addressing social determinants and expanding care coordination with community partners, provide opportunity to better meet patients' needs and decrease hospital readmission in high-risk patients.
RAF1 variants causing biventricular hypertrophic cardiomyopathy in two preterm infants: further phenotypic delineation and review of literature
Authors: Thompson Danielle , Patrick-Esteve Jessica , Surcouf Jeffrey W. , Rivera Dana , Castellanos Bianca , Desai Pooja , Lilje Christian , Lacassie Yves , Marble Michael , Zambrano Regina
Published: August 2017

Noonan syndrome (NS) is an autosomal dominant disorder characterized by distinctive facial features, short neck, short stature, congenital heart defects, pectus deformities, and variable developmental delays. NS is genetically heterogeneous as pathogenic variants in several genes involved in the Ras/mitogen-activated protein kinase pathway have been associated with a NS phenotype. Overall, 50% of patients harbor pathogenic variants in PTPN11, whereas 3–17% of patients have variants in RAF1. We present two premature neonates with progressive biventricular hypertrophy found to have RAF1 variants in the CR2 domain. Molecular testing in patient 1 revealed a missense variant of a highly conserved residue c.782 C>G (p.P261R). This variant has been reported once with fatal outcome. Patient 2 also had a missense variant in a highly conserved neighboring residue c.770 C>T (p.S257L). This variant has been previously reported, most recently associated with the development of pulmonary arterial hypertension. Both our patients had prenatal findings of polyhydramnios, short long bones, hydrops fetalis, and cardiac anomalies with progressive biventricular hypertrophic cardiomyopathy. Both patients had a lethal outcome. Our findings further support the pathogenicity and lethality of p.P261R, and the need to monitor for pulmonary arterial hypertension in p.S257L. In addition, the second patient was presented with progressive hydrocephalus due to aqueductal stenosis. This could be related to the NS phenotype. More cases with this association are needed to confirm this finding.
Immunohistochemical Differentiation of Plasmacytoid Urothelial Carcinoma From Secondary Carcinoma Involvement of the Bladder
Authors: Borhan Walaa M. , Cimino-Mathews Ashley M. , Montgomery Elizabeth A. , Epstein Jonathan I.
Published: August 2017

Plasmacytoid urothelial carcinoma (UC) is a rare variant of UC that can histologically mimic metastatic cancer involving the urinary bladder. A total of 45 cases of plasmacytoid UC were collected and reviewed histologically. The following immunohistochemical markers were performed: CDX2; polyclonal carcinoembryonic antigen (p-CEA); gross cystic disease fluid protein 15 (GCDFP-15); mammaglobin; estrogen receptor (ER); progesterone receptor (PR); GATA 3 and uroplakin II. In all cases, the plasmacytoid variant of UC lacked expression of ER and mammaglobin. In contrast, GCPDFP-15, PR, CDX2 and p-CEA showed positive staining in 11 (24.4%), 6 (13.3%), 8 (17.7%), and 22 (48.8%) cases, respectively. GCPDFP-15 was expressed in 4/8 female cases with 1 concurrently focally (+2) expressing PR. GATA 3 and uroplakin II was positive in 37/45 cases (82.2%) and 15/45 (33.3%) cases, respectively. A tissue microarray with 40 cases of infiltrating lobular carcinoma of the breast was stained for uroplakin II, and was negative in all cases. Tissue microarrays with 46 cases of gastric signet ring cell adenocarcinomas were all negative for GCDFP-15, ER, PR, GATA3, uroplakin II, and mammaglobin. A panel of stains including mammaglobin, ER, and uroplakin II is recommended to exclude metastatic lobular breast carcinoma to the bladder in cases where a conventional UC component is not present. Immunohistochemistry for CDX2 and p-CEA cannot be utilized to differentiate signet ring cell adenocarcinoma of the gastrointestinal tract from plasmacytoid UC; GATA3 or uroplakin II immunoreactivity can rule out a gastric primary given their negativity in signet ring cell adenocarcinoma of the stomach.
Norepinephrine Contributes to Enterocyte Damage in Septic Shock Patients: A Prospective Cohort Study
Authors: Habes Quirine L.M. , van Ede Lisa , Gerretsen Jelle , Kox Matthijs , Pickkers Peter
Published: August 2017

Objectives:

In septic patients, both systemic inflammation and splanchnic hypoperfusion may cause enterocyte damage. Catecholamines may exert additional detrimental effects on mesenteric blood flow in these patients, and thereby contribute to this damage. Enterocyte damage itself results in impairment of gut barrier function and consequent translocation of bacteria/toxins. This may contribute to multiple organ failure and death by sustaining or amplifying the systemic inflammatory response. The aim of the study was 2-fold: to investigate which factors contribute to enterocyte damage in septic patients, and to assess whether enterocyte damage is associated with a sustained or amplified systemic inflammatory response.

Methods:

In this prospective observational cohort study in 129 patients with septic shock admitted to the ICU, we serially measured plasma levels of Intestinal Fatty Acid-Binding Protein (I-FABP, a marker for enterocyte damage) and of cytokines Tumor Necrosis Factor (TNF)-α, Interferon (IFN)-y, Interleukin (IL)-1β, IL-6, IL-8, IL-1 Receptor Antagonist (RA), and IL-10. Clinical data were collected from electronic patient files.

Results:

A total of 129 patients were included in the study. The median age of the patients was 67 years [56–74]. The median norepinephrine infusion rate was 0.2 μg/kg/min [0.1–0.5]. Overall, 28-day mortality was 31 (24%). Similar to previous work, I-FABP levels at admission were independently associated with mortality (odds ratio 3.101 [1.138–8.448]). Acute Physiology and Chronic Health Evaluation II score and an increase in norepinephrine infusion rate between days 1 and 3 were independently associated with area under curve I-FABP levels, whereas mean arterial pressure and creatinine levels were not. No correlations were found between any of the measured cytokines and plasma I-FABP levels. Furthermore, high I-FABP levels were not related with the subsequent course of cytokine levels.

Conclusions:

In patients with septic shock, norepinephrine use is associated with more enterocyte damage. Although enterocyte damage is associated with increased 28-day mortality, it is not associated with a sustained or amplified systemic inflammatory response.
Intestinal and Limb Ischemic Preconditioning Provides a Combined Protective Effect in the Late Phase, But not in the Early Phase, Against Intestinal Injury Induced by Intestinal Ischemia–Reperfusion in Rats
Authors: Yang Bo , Chen Ye , Long Yan-Hong , Fan Xin , Liu Ke-Xuan , Wang Xiao-Bin , Zhou Jun
Published: August 2017

Intestinal ischemia/reperfusion (I/R) injury is associated with high morbidity and mortality. This study aimed to compare the protective efficacy of intestinal ischemic preconditioning (IIPC) and limb ischemic preconditioning (LIPC) against intestinal I/R injury and investigate their combined protective effect and the underlying mechanism. Male Sprague–Dawley rats were pretreated with IIPC, LIPC, or IIPC plus LIPC (combined), and intestinal I/R or sham operation was performed. The animals were sacrificed at 2 and 24 h after reperfusion and then blood and tissue samples were harvested for further analyses. In additional groups of animals, a 7-day survival study was conducted. The results showed that ischemic preconditioning (IPC) improved the survival rate and attenuated intestinal edema, injury, and apoptosis. IPC decreased the levels of tumor necrosis factor-α, interleukin -6, malondialdehyde and myeloperoxidase, and increased the activity of superoxide dismutase in serum and intestine after the I/R event. IPC downregulated the expression of Toll-like receptor-4 (TLR4) and nuclear factor-kappa B (NF-κB). The effect of combined pretreatment was better than that of single pretreatment in the late phase (24 h), but not in the early phase (2 h). The study demonstrated that IPC could significantly attenuate intestinal injury induced by intestinal I/R via inhibiting inflammation, oxidative stress, and apoptosis. IIPC and LIPC conferred no synergy in protecting I/R-induced intestinal injury in the early phase, but combined preconditioning had clearly stronger protection in the late phase, which was associated with the inhibition of the activated TLR4/NF-κB signaling pathway. It suggested that LIPC or combined preconditioning could potentially be applied in the clinical settings of surgical patient care.
A Model for Genome-First Care: Returning Secondary Genomic Findings to Participants and Their Healthcare Providers in a Large Research Cohort
Authors: Schwartz Marci L. B. , McCormick Cara Zayac , Lazzeri Amanda L. , Lindbuchler D’Andra M. , Hallquist Miranda L. G. , Manickam Kandamurugu , Buchanan Adam H. , Rahm Alanna Kulchak , Giovanni Monica A. , Frisbie Lauren , Flansburg Carroll N. , Davis F. Daniel , Sturm Amy C. , Nicastro Christine , Lebo Matthew S. , Mason-Suares Heather , Mahanta Lisa Marie , Carey David J. , Williams Janet L. , Williams Marc S. , Ledbetter David H. , Faucett W. Andrew , Murray Michael F.
Published: August 2017

Background

Research cohorts with linked genomic data exist, or are being developed, at many research centers. Within any such “sequenced cohort” of more than 100 participants, it is likely that there are participants with previously undisclosed risk for life-threatening monogenic diseases that could be identified with targeted analysis of their existing data. Identification of such disease-associated findings are not usually primary to the enrollment research goals. At Geisinger Health System, MyCode®Community Health Initiative (MyCode) participants represent one such large sequenced cohort. Since 2013, MyCode participants in discovery research have been consented for secondary analysis of their existing research genomic sequences to allow delivery of medically actionable findings to them and their healthcare providers. This return of genomic results program was developed to manage an anticipated 3.5% of MyCode participants who will receive clinically confirmed genomic variants from an approved gene list out of more than 150,000 total participants. Risk-associated DNA sequences alone without any clinical parameter, prompt “genome-first” follow-up encounters.

Methods

This article describes our process for generating clinical grade results from research-based genomic sequencing data, delivering results to patients and their providers, facilitating targeted clinical evaluations of patients and promoting cascade testing of at-risk relatives. We also summarize our early data about the results generated during this process and our ability to contact patients and their providers to disclose the information.

Results

This process has been used to generate 343 results on 339 patients. 93% of patients with a result have been successfully contacted about their results as evidenced by direct interaction about their result with the research team or a healthcare provider. 222 healthcare providers have been notified of a result on one or more patient through this result delivery process.

Conclusions

Here we describe the existing GHS model to deliver genomic data into the electronic medical record and the clinical interactions that are prompted and supported. Elements of this genome-first care model can be applied in other healthcare settings and in national efforts, such as “All of Us”, that wish to establish programs for returning genomic results to research participants.
Distinct Laminar Processing of Local and Global Context in Primate Primary Visual Cortex
Authors: Bijanzadeh Maryam , Nurminen Lauri , Merlin Sam , Angelucci Alessandra
Published: August 2017

Visual perception is profoundly affected by spatial context. In visual cortex, neuronal responses to stimuli inside their receptive field (RF) are suppressed by contextual stimuli in the RF surround (surround suppression). How do neuronal RFs integrate information across visual space, and what role do different cortical layers play in the processing of spatial context? By recording simultaneously across all layers of macaque primary visual cortex, while presenting visual stimuli at increasing distances from the recorded cells RF, we find that near vs. far stimuli activate distinct layers. Stimuli in the near-surround evoke the earliest subthreshold responses in superficial and deep layers, and cause the earliest surround suppression of spiking responses in superficial layers. Instead, far-surround stimuli evoke the earliest subthreshold responses in feedback-recipient layers, i.e. 1 and the lower half of the deep layers, and suppress visually-evoked spiking responses almost simultaneously in all layers, except 4C, where suppression emerges latest. Our results reveal unique contributions of the cortical layers to the processing of local and global spatial context, and suggest distinct underlying circuits for local and global signal integration.
Kinesin-6 KIF20B is required for efficient cytokinetic furrowing and timely abscission in human cells
Authors: Janisch Kerstin M. , McNeely Katrina C. , Dardick Joseph M. , Lim Samuel H. , Dwyer Noelle D.
Published: August 2017

Cytokinesis requires the cooperation of many cytoskeletal and membrane regulators. Most of the major players required for cytokinesis are known, but the temporal regulation and adaptations for different cell types are less understood. KIF20B (previously called MPHOSPH1 or MPP1) is a member of the Kinesin-6 family, which also includes the better-known members KIF23/MKLP1 and KIF20A/MKLP2. Previously, we showed that mouse Kif20b is involved in cerebral cortex growth and midbody organization of neural stem cells. Here we show that KIF20B has a cell-autonomous role in cytokinesis in isolated human cells. It localizes to microtubules of the central spindle and midbody throughout cytokinesis, at sites distinct from the other Kinesin-6 family members. KIF20B is not required for central spindle or midbody assembly, but affects midbody shape and late maturation steps. KIF20B appears to temporally regulate both furrow ingression and abscission.
A quantitative chemotherapy genetic interaction map reveals new factors associated with PARP inhibitor resistance
Authors: Hu Hsien-Ming , Zhao Xin , Kaushik Swati , Robillard Lilliane , Barthelet Antoine , Lin Kevin K. , Simmons Andy D. , Raponi Mitch , Harding Thomas C. , Bandyopadhyay Sourav
Published: August 2017

Nearly every cancer patient is treated with chemotherapy yet our understanding of factors that dictate response and resistance to such agents remains limited. We report the generation of a quantitative chemical-genetic interaction map in human mammary epithelial cells that charts the impact of knockdown of 625 cancer and DNA repair related genes on sensitivity to 29 drugs, covering all classes of cancer chemotherapeutics. This quantitative map is predictive of interactions maintained in cancer cell lines and can be used to identify new cancer-associated DNA repair factors, predict cancer cell line responses to therapy and prioritize drug combinations. We identify thatGPBP1loss in breast and ovarian cancer confers resistance to cisplatin and PARP inhibitors through the regulation of genes involved in homologous recombination. This map may help navigate patient genomic data and optimize chemotherapeutic regimens by delineating factors involved in the response to specific types of DNA damage.
First Draft Genome Sequence of the Pathogenic FungusLomentospora prolificans(formerlyScedosporium prolificans)
Authors: Luo Ruibang , Zimin Aleksey , Workman Rachael , Fan Yunfan , Pertea Geo , Grossman Nina , Wear Maggie P. , Jia Bei , Miller Heather , Casadevall Arturo , Timp Winston , Zhang Sean X. , Salzberg Steven L.
Published: August 2017

Here we describe the sequencing and assembly of the pathogenic fungusLomentospora prolificansusing a combination of short, highly accurate Illumina reads and additional coverage in very long Oxford Nanopore reads. The resulting assembly is highly contiguous, containing a total of 37,630,066 bp with over 98% of the sequence in just 26 scaffolds. Annotation identified 8,656 protein-coding genes. Pulsed-field gel analysis suggests that this organism contains at least 7 and possibly 11 chromosomes, the two longest of which have sizes corresponding closely to the sizes of the longest scaffolds, at 6.6 and 5.7 Mb.
Applying expression profile similarity for discovery of patient-specific functional mutations
Authors: Meng Guofeng
Published: August 2017

The progress of cancer genome sequencing projects yields unprecedented information of mutations for numerous patients. However, the complexity of mutation profiles of patients hinders the further understanding of mechanisms of oncogenesis. One basic question is how to uncover mutations with functional impacts. In this work, we introduce a computational method to predict functional somatic mutations for each of patient by integrating mutation recurrence with similarity of expression profiles of patients. With this method, the functional mutations are determined by checking the mutation enrichment among a group of patients with similar expression profiles. We applied this method to three cancer types and identified the functional mutations. Comparison of the predictions for three cancer types suggested that most of the functional mutations were cancer-type-specific with one exception to p53. By checking prediction results, we found that our method effectively filtered non-functional mutations resulting from large protein sizes. In addition, this methods can also perform functional annotation to each patient to describe their association with signalling pathways or biological processes. In breast cancer, we predicted “cell adhesion” and other mutated gene associated terms to be significantly enriched among patients.
Heritable cognitive and psychopathology factors in youth are predicted by brain fronto-temporal white matter pathway
Authors: Alnæs Dag , Kaufmann Tobias , Doan Nhat Trung , Córdova-Palomera Aldo , Wang Yunpeng , Bettella Francesco , Moberget Torgeir , Andreassen Ole A. , Westlye Lars T.
Published: August 2017

A healthy transition from adolescence to adulthood relies on a continuous individual adaptation to a dynamic environment. Here, we employed data driven multivariate approaches to derive both general cognitive and psychopathology factors as well as brain phenotypes in children and adolescents in the publicly available PNC sample. We identified a distinct brain white matter pattern which proved central for prediction of heritable cognition and psychopathology scores, highlighting the importance of fronto-temporal connections for intellectual and mental development.
An improved method for the expression screening of membrane protein-GFP fusions in yeast
Authors: Baldock Darren , Sheldon Judith , Tailor Ravi , Green Katherine , Ray John , Singh Shradha , Brocklehurst Kathryn
Published: August 2017

The expression and purification of membrane proteins is an extremely challenging area of work within Protein Science. Membrane proteins are required for compound screening and structure determination in industry. Here we describe some new and innovative methodology in developing the membrane protein GFP fusion primary expression screening in yeast. This methodology enables the expression of membrane proteins fused to GFP in bothSaccharomyces cerevisiaeandPichia pastorissystems. This capability helps facilitate screening of constructs to establish which are suitable for membrane protein production for compound screening and structure determination

In terms of the primary screening work, we have developed both agar plate and liquid plate expression methodology in yeast. The two approaches correspond well, but the agar plate method is more rapid and we have shown it to have the advantage of allowing cells to be taken directly into confocal microscopy for immediate cell localisation data. Innovative work to extend the methanol induction time in thePichiaagar plate method established good differentiation from the background. A novel agar plate method was also developed forS.cerevisiaewhich is also presented. These screening methods allow triaging of constructs for either membrane protein preps for biochemical assays or progression to fluorescence size exclusion chromatography; where various detergents can be screened to determine the most appropriate for membrane protein solubilisation, the starting point for purification, crystallisation and structure determination.

Membrane targets depicted to demonstrate the improved primary screening methodology are a copper transporter Ctr1p fromS.cerevisiaeand a water transporter Aqp4 from human origin.

Highlights

An improved method for the production of recombinant MP-GFP fusions in yeast is presented using agar plates.

An agar plate method for MP-GFP expression screening is described forPichia pastoris, with improved induction methodology by the simple addition of methanol, allowing longer induction times for expression clarity.

A new simple rapid agar plate method for MP-GFP expression screening is described forSaccharomyces cerevisiae.

Cells can be taken directly from agar plates into confocal microscopy studies for immediate cell localisation data and triaging.

Liquid plate based screening methods are also described for both yeasts in comparison, to show there is corresponding data, helping validate the new agar plate methods.
Ageing synaptic vesicles are inactivated by contamination with SNAP25
Authors: Truckenbrodt Sven , Viplav Abhiyan , Jähne Sebastian , Vogts Angela , Denker Annette , Wildhagen Hanna , Fornasiero Eugenio F. , Rizzoli Silvio O.
Published: August 2017

Old organelles can become a hazard to cellular function, by accumulating molecular damage. Mechanisms that identify aged organelles, and prevent them from participating in cellular reactions, are therefore necessary. We describe here one such mechanism for the synaptic vesicle recycling pathway. Using cultured hippocampal neurons, we found that newly synthesized vesicle proteins were incorporated in the active (recycling) pool, and were preferentially employed in neurotransmitter release. They remained in use for up to ~24 hours, during which they recycled up to a few hundred times. We could only detect one change in the molecular composition of the vesicles, an apparent accumulation of SNAP25 in the aged synaptic vesicles. Overexpression of SNAP25, both in wild-type form or in vesicle-bound form, inhibited exocytosis and promoted the co-localization of the vesicle molecules with a recycling endosome marker. This is in line with the hypothesis that the SNAP25 contamination causes the inactivation of the aged vesicles. The SNAP25 overexpression effect could be alleviated by co-expressing the vesicle-associated molecule CSPa, which has been previously shown to be involved in chaperoning SNAP25 in the vesicle priming process. Overall, these results suggest that newly synthesized vesicle molecules are preferred in vesicle recycling, probably through a mechanism that renders their priming more efficient than that of aged vesicles.
Crystal structure of tetraaquabis(1,3-dimethyl-2,6-dioxo-7H-purin-7-ido-κN7)cobalt(II)
Authors: El Hamdani Hicham , El Amane Mohammed , Duhayon Carine
Published: August 2017

The title complex, [Co(C7H7N4O2)2(H2O)4], comprises mononuclear molecules consisting of a CoIIion, two deprotonated theophylline ligands (systematic name: 1,3-dimethyl-7H-purine-2,6-dione) and four coordinating water molecules. The CoIIatom lies on an inversion centre and has a slightly distorted octahedral coordination environment, with two N atoms of twotrans-oriented theophylline ligands and the O atoms of four water molecules. An intramolecular hydrogen bond stabilizes this conformation. A three-dimensional supramolecular network structure is formed by intermolecular O—H...O and O—H...N hydrogen bonds.
Accounts of nature and the nature of accounts
Authors: Russell Shona , Milne Markus J. , Dey Colin
Published: August 2017

Purpose

The purpose of this paper is to review and synthesise academic research in environmental accounting and demonstrate its shortcomings. It provokes scholars to rethink their conceptions of “accounts” and “nature”, and alongside others in thisAAAJspecial issue, provides the basis for an agenda for theoretical and empirical research that begins to “ecologise” accounting.

Design/methodology/approach

Utilising a wide range of thought from accounting, geography, sociology, political ecology, nature writing and social activism, the paper provides an analysis and critique of key themes associated with 40 years research in environmental accounting. It then considers how that broad base of work in social science, particularly pragmatic sociology (e.g. Latour, Boltanksi and Thévenot), could contribute to reimagining an ecologically informed accounting.

Findings

Environmental accounting research overwhelmingly focuses on economic entities and their inputs and outputs. Conceptually, an “information throughput” model dominates. There is little or no environment in environmental accounting, and certainly no ecology. The papers in thisAAAJspecial issue contribute to these themes, and alongside social science literature, indicate significant opportunities for research to begin to overcome them.

Research limitations/implications

This paper outlines and encourages the advancement of ecological accounts and accountabilities drawing on conceptual resources across social sciences, arts and humanities. It identifies areas for research to develop its interdisciplinary potential to contribute to ecological sustainability and social justice.

Originality/value

How to “ecologise” accounting and conceptualise human and non-human entities has received little attention in accounting research. This paper andAAAJspecial issue provides empirical, practical and theoretical material to advance further work.
Ecology-centred accounting for biodiversity in the production of a blanket bog
Authors: Cuckston Thomas
Published: August 2017

Purpose

The purpose of this paper is to analyse the role of ecology-centred accounting for biodiversity in efforts to conserve biodiversity.

Design/methodology/approach

The paper examines a case study of biodiversity conservation efforts to restore a degraded blanket bog habitat. The analysis adopts a social nature perspective, which sees the social and the natural as inseparably intertwined in socio-ecological systems: complexes of relations between (human and non-human) actors, being perpetually produced by fluid interactions. Using a theoretical framework from the geography literature, consisting of four mutually constitutive dimensions of relations – territory, scale, network, and place (TSNP) – the analysis examines various forms of accounting for biodiversity that are centred on this blanket bog.

Findings

The analysis finds that various forms of ecology-centred accounting for biodiversity have rendered this blanket bog visible and comprehensible in multiple ways, so as to contribute towards making this biodiversity conservation thinkable and possible.

Originality/value

This paper brings theorising from geography, concerning the social nature perspective and the TSNP framework, into the study of accounting for biodiversity. This has enabled a novel analysis that reveals the productive force of ecology-centred accounting for biodiversity, and the role of such accounting in organising the world so as to produce socio-ecological systems that aid biodiversity conservation.