bluuebunny/crossref_metadata_2025 huggingface dataset:
Generating Bona Fide Mammalian Prions with Internal Deletions
Authors: Munoz-Montesino Carola , Sizun Christina , Moudjou Mohammed , Herzog Laetitia , Reine Fabienne , Chapuis Jérôme , Ciric Danica , Igel-Egalon Angelique , Laude Hubert , Béringue Vincent , Rezaei Human , Dron Michel
Published: May 2016

Mammalian prions are PrP proteins with altered structures causing transmissible fatal neurodegenerative diseases. They are self-perpetuating through formation of beta-sheet-rich assemblies that seed conformational change of cellular PrP. Pathological PrP usually forms an insoluble protease-resistant core exhibiting beta-sheet structures but no more alpha-helical content, loosing the three alpha-helices contained in the correctly folded PrP. The lack of a high-resolution prion structure makes it difficult to understand the dynamics of conversion and to identify elements of the protein involved in this process. To determine whether completeness of residues within the protease-resistant domain is required for prions, we performed serial deletions in the helix H2 C terminus of ovine PrP, since this region has previously shown some tolerance to sequence changes without preventing prion replication. Deletions of either four or five residues essentially preserved the overall PrP structure and mutant PrP expressed in RK13 cells were efficiently converted into bona fide prions upon challenge by three different prion strains. Remarkably, deletions in PrP facilitated the replication of two strains that otherwise do not replicate in this cellular context. Prions with internal deletion were self-propagating and
de novo
infectious for naive homologous and wild-type PrP-expressing cells. Moreover, they caused transmissible spongiform encephalopathies in mice, with similar biochemical signatures and neuropathologies other than the original strains. Prion convertibility and transfer of strain-specific information are thus preserved despite shortening of an alpha-helix in PrP and removal of residues within prions. These findings provide new insights into sequence/structure/infectivity relationship for prions.

IMPORTANCE
Prions are misfolded PrP proteins that convert the normal protein into a replicate of their own abnormal form. They are responsible for invariably fatal neurodegenerative disorders. Other aggregation-prone proteins appear to have a prion-like mode of expansion in brains, such as in Alzheimer's or Parkinson's diseases. To date, the resolution of prion structure remains elusive. Thus, to genetically define the landscape of regions critical for prion conversion, we tested the effect of short deletions. We found that, surprisingly, removal of a portion of PrP, the C terminus of alpha-helix H2, did not hamper prion formation but generated infectious agents with an internal deletion that showed characteristics essentially similar to those of original infecting strains. Thus, we demonstrate that completeness of the residues inside prions is not necessary for maintaining infectivity and the main strain-specific information, while reporting one of the few if not the only bona fide prions with an internal deletion.
Viral Evasion and Manipulation of Host RNA Quality Control Pathways
Authors: Hogg J. Robert
Published: May 2016

Viruses have evolved diverse strategies to maximize the functional and coding capacities of their genetic material. Individual viral RNAs are often used as substrates for both replication and translation and can contain multiple, sometimes overlapping open reading frames. Further, viral RNAs engage in a wide variety of interactions with both host and viral proteins to modify the activities of important cellular factors and direct their own trafficking, packaging, localization, stability, and translation. However, adaptations increasing the information density of small viral genomes can have unintended consequences. In particular, viral RNAs have developed features that mark them as potential targets of host RNA quality control pathways. This minireview focuses on ways in which viral RNAs run afoul of the cellular mRNA quality control and decay machinery, as well as on strategies developed by viruses to circumvent or exploit cellular mRNA surveillance.
Human Cytomegalovirus pUL93 Links Nucleocapsid Maturation and Nuclear Egress
Authors: DeRussy Bernadette M. , Boland Molly T. , Tandon Ritesh
Published: May 2016

Human cytomegalovirus (HCMV) pUL93 and pUL77 are both essential for virus growth, but their functions in the virus life cycle remain mostly unresolved. Homologs of pUL93 and pUL77 in herpes simplex virus 1 (HSV-1) and pseudorabies virus (PRV) are known to interact to form a complex at capsid vertices known as the capsid vertex-specific component (CVSC), which likely stabilizes nucleocapsids during virus maturation and also aids in nuclear egress. In herpesviruses, nucleocapsids assemble and partially mature in nuclear replication compartments and then travel to the inner nuclear membrane (INM) for nuclear egress. The factors governing the recruitment of nucleocapsids to the INM are not known. Kinetic analysis of pUL93 demonstrates that this protein is expressed late during infection and localizes primarily to the nucleus of infected cells. pUL93 associates with both virions and capsids and interacts with the components of the nuclear egress complex (NEC), namely, pUL50, pUL53, and pUL97, during infection. Also, multiple regions in pUL93 can independently interact with pUL77, which has been shown to help retain viral DNA during capsid assembly. These studies, combined with our earlier report of an essential role of pUL93 in viral DNA packaging, indicate that pUL93 serves as an important link between nucleocapsid maturation and nuclear egress.

IMPORTANCE
HCMV causes life-threatening disease and disability in immunocompromised patients and congenitally infected newborns. In this study, we investigated the functions of HCMV essential tegument protein pUL93 and determined that it interacts with the components of the nuclear egress complex, namely, pUL50, pUL53, and pUL97. We also found that pUL93 specifically interacts with pUL77, which helps retain viral DNA during capsid assembly. Together, our data point toward an important role of pUL93 in linking virus maturation to nuclear egress. In addition to expanding our knowledge of the process of HCMV maturation, information from these studies will also be utilized to develop new antiviral therapies.
Release of Infectious Hepatitis C Virus from Huh7 Cells Occurs via a
trans
-Golgi Network-to-Endosome Pathway Independent of Very-Low-Density Lipoprotein Secretion
Authors: Mankouri Jamel , Walter Cheryl , Stewart Hazel , Bentham Matthew , Park Wei Sun , Heo Won Do , Fukuda Mitsunori , Griffin Stephen , Harris Mark
Published: May 2016

The release of infectious hepatitis C virus (HCV) particles from infected cells remains poorly characterized. We previously demonstrated that virus release is dependent on the endosomal sorting complex required for transport (ESCRT). Here, we show a critical role of
trans
-Golgi network (TGN)-endosome trafficking during the assembly, but principally the secretion, of infectious virus. This was demonstrated by both small interfering RNA (siRNA)-mediated silencing of TGN-associated adaptor proteins and a panel of dominant negative (DN) Rab GTPases involved in TGN-endosome trafficking steps. Importantly, interfering with factors critical for HCV release did not have a concomitant effect on secretion of triglycerides, ApoB, or ApoE, indicating that particles are likely released from Huh7 cells via pathways distinct from that of very-low-density lipoprotein (VLDL). Finally, we show that HCV NS2 perturbs TGN architecture, redistributing TGN membranes to closely associate with HCV core protein residing on lipid droplets. These findings support the notion that HCV hijacks TGN-endosome trafficking to facilitate particle assembly and release. Moreover, although essential for assembly and infectivity, the trafficking of mature virions is seemingly independent of host lipoproteins.

IMPORTANCE
The mechanisms by which infectious hepatitis C virus particles are assembled and released from the cell are poorly understood. We show that the virus subverts host cell trafficking pathways to effect the release of virus particles and disrupts the structure of the Golgi apparatus, a key cellular organelle involved in secretion. In addition, we demonstrate that the mechanisms used by the virus to exit the cell are distinct from those used by the cell to release lipoproteins, suggesting that the virus effects a unique modification to cellular trafficking pathways.
Tegument Protein ORF45 Plays an Essential Role in Virion Morphogenesis of Murine Gammaherpesvirus 68
Authors: Jia Xing , Shen Sheng , Lv Ying , Zhang Ziwei , Guo Haitao , Deng Hongyu
Published: May 2016

Tegument proteins play critical roles in herpesvirus morphogenesis. ORF45 is a conserved tegument protein of gammaherpesviruses; however, its role in virion morphogenesis is largely unknown. In this work, we determined the ultrastructural localization of murine gammaherpesvirus 68 (MHV-68) ORF45 and found that this protein was incorporated into virions around the site of host-derived vesicles. Notably, the absence of ORF45 inhibited nucleocapsid egress and blocked cytoplasmic virion maturation, demonstrating that ORF45 is essential for MHV-68 virion morphogenesis.
Stathmin is a highly sensitive and specific biomarker for vulvar high-grade squamous intraepithelial lesions
Authors: Nooij Linda S , Dreef Enno J , Smit Vincent T H B M , van Poelgeest Mariëtte I E , Bosse Tjalling
Published: May 2016

Aims

Differentiating between human papilloma virus-dependent vulvar low-grade and high-grade squamous intraepithelial lesions (LSILs and HSILs) remains difficult in selected cases. Stathmin, a protein involved in cell cycle progression, might be a useful additional marker for this differentiation. The aim of this study was to investigate the additional diagnostic value of stathmin expression in vulvar intraepithelial neoplastic (VIN) lesions.

Methods

Immunohistochemical analysis was used to evaluate stathmin, P16 and Ki67 expression in 91 samples, including LSILs (n=16), HSILs (n=50), differentiated VIN (dVIN; n=10), lichen sclerosis (LS; n=10) and normal vulvar tissue (n=5).

Results

Stathmin was expressed in more than one-third of the epithelium in all HSILs and in 20% of LSILs. P16 and Ki67 were expressed in more than one-third of the epithelium in 94% of HSILs and in 13% and 40% of LSILs, respectively. Stathmin was expressed in more than one-third of the epithelium in 10% of the dVIN and in none of the LS or normal lesions. P16 and Ki67 expression was not present in more than one-third of the epithelium in any of these lesions. The sensitivity of stathmin for differentiating between LSILs and HSILs was 100% compared with a sensitivity of 94% for both p16 and Ki67. The specificity of stathmin, p16 and Ki67 was 80%, 87% and 60%, respectively.

Conclusions

Stathmin is a highly sensitive and specific biomarker for the diagnosis of vulvar HSIL. In addition to the more commonly used immunohistochemical markers p16 and Ki67, stathmin can be a useful diagnostic tool for identifying HSILs, especially in cases in which differentiating between LSIL and HSIL is difficult.
Effects on cigarette consumption of a work–family supportive organisational intervention: 6-month results from the work, family and health network study
Authors: Hurtado David A , Okechukwu Cassandra A , Buxton Orfeu M , Hammer Leslie , Hanson Ginger C , Moen Phyllis , Klein Laura C , Berkman Lisa F
Published: May 2016

Background

Observational studies have linked work–family issues with cigarette consumption. This study examined the 6-month effects on cigarette consumption of a work–family supportive organisational intervention among nursing home workers.

Methods

Group randomised controlled trial where 30 nursing homes across New England states were randomly assigned to either usual practice or to a 4-month intervention aimed at reducing work–family conflict via increased schedule control and family supportive supervisory behaviours (FSSB). Cigarette consumption was based on self-reported number of cigarettes per week, measured at the individual level.

Results

A total of 1524 direct-care workers were enrolled in the trial. Cigarette consumption was prevalent in 30% of the sample, consuming an average of 77 cigarettes/week. Smokers at intervention sites reduced cigarette consumption by 7.12 cigarettes, while no reduction was observed among smokers at usual practice sites (b=−7.12, 95% CI −13.83 to −0.40, p<0.05) (d=−0.15). The majority of smokers were US-born White nursing assistants, and among this subgroup, the reduction in cigarette consumption was stronger (b=−12.77, 95% CI −22.31 to −3.22, p<0.05) (d=−0.27). Although the intervention prevented a decline in FSSB (d=0.08), effects on cigarette consumption were not mediated by FSSB.

Conclusions

Cigarette consumption was reduced among smokers at organisations where a work–family supportive intervention was implemented. This effect, however, was not explained by specific targets of the intervention, but other psychosocial pathways related to the work–family interface.

Trial registration number

NCT02050204; results.
Optimal planting date, row width, and critical weed-free period for grain amaranth and quinoa grown in Ontario, Canada
Authors: Nurse Robert E. , Obeid Kristen , Page Eric R.
Published: May 2016

The popularity of grain amaranth and quinoa is growing in Ontario, increasing the interest in their cultivation. Two experiments were conducted in southern Ontario in 2013 and 2014 to evaluate optimal planting date (every two weeks from early May to late July), row width (38 or 75 cm), and critical weed-free period (the component of the critical period of weed control that defines the number of days that the crop must remain weed-free to prevent yield loss) in each crop. Grain amaranth and quinoa both reached physiological maturity and produced yields when planting dates ranged from mid-May to late-June. When either crop was seeded in July, yields decreased by more than 50% and the crop did not always reach maturity before the first frost. While row width did not have an impact on yield, it is advisable to grow the crops in wider rows (75 cm) to facilitate weed control early in the growing season (up to 30 d after emergence (DAE)). The critical weed-free period was 24 and 16 DAE for grain amaranth and quinoa, respectively, after which yields were maintained at 95% of the weed-free control. Based on these data, both crops could easily be integrated into the normal cropping rotations found in southern Ontario.
Neuronal diversity and their spine density in the hippocampal complex of the House Crow (Corvus splendens), a food-storing bird
Authors: Srivastava U.C. , Singh Durgesh , Kumar Prashant , Singh Sippy
Published: May 2016

Hippocampus, one of the parts included in the limbic system, is involved in various functions such as learning, memory, food-storing behavior, and sexual discrimination. Neuronal classes of the hippocampal complex in food-storing birds have been also reported, but the study lacks details pertaining to neuronal characteristics and the spine density of the neurons in different subfields of the hippocampus. Hence, the present study was undertaken with the aim to explore the morphology of neurons and the spines present on their dendrites within the hippocampal complex of the House Crow (Corvus splendens Vieillot, 1817), a food-storing Indian bird, and to compare it with previously reported nonfood-storing bird species. It was observed that the hippocampus of C. splendens harbors diverse neuronal classes with substantial percentages of pyramidal neurons, well-developed local circuit neurons, and high spine density. All these neuronal specializations in C. splendens can be related with the food-storing behavior of the bird, which itself is an advantage over nonfood-storing birds.
Trophic biology and migratory patterns of sympatric Dolly Varden (Salvelinusmalma) and Arctic char (Salvelinusalpinus)
Authors: Dennert A.M. , May-McNally S.L. , Bond M.H. , Quinn T.P. , Taylor E.B.
Published: May 2016

The trophic ecology (diet and head morphology) and migration patterns of two closely related salmonid fishes, Arctic char (Salvelinus alpinus (L., 1758)) and Dolly Varden (Salvelinus malma (Walbaum, 1792)), were examined in tributaries of Lake Aleknagik, southwestern Alaska, to test for differentiation between species. Schoener’s index of proportional overlap and multivariate analyses of diets suggested that these species had significantly different trophic niches. Arctic char and the largest individuals of both species had the most diverse diets, and sockeye salmon (Oncorhynchus nerka (Walbaum, 1792)) eggs dominated the diet of both species, especially Arctic char. Arctic char had larger jaws and wider heads than Dolly Varden of similar body length, which may contribute to interspecific diet difference. The species also differed in migration patterns; otolith microchemistry indicated that juvenile Arctic char were produced by nonanadromous mothers, whereas the mothers of the Dolly Varden had been to sea in the season prior to spawning. The species also segregate in spawning habitat (Arctic char in the lakes and Dolly Varden in streams), as well as in juvenile rearing habitat. Our study provides the first evidence of divergent feeding and migratory ecology between sympatric juvenile Arctic char and Dolly Varden, differences that may constrain hybridization and introgression between them.
Off-Site Lime Stabilisation as an Option to Treat Pit Latrine Faecal Sludge for Emergency and Existing On-Site Sanitation Systems
Authors: Greya Wilson , Thole Bernard , Anderson Catherine , Kamwani Flavius , Spit Jan , Mamani Grover
Published: May 2016

Off-site lime stabilisation for treating faecal sludge was assessed by undertaking small-scale (35 L) and large-scale (600 L) field trials in Blantyre, Malawi. Hydrated lime was dosed to maintain pH 10, pH 10.5, pH 11, pH 11.5, and pH 12 depending on the buffer capacity of the faecal sludge in the four replica small-scale field trials. Significant reduction of E. coli to below the detection limit of 104 CFU/100 mL within 1 hour of treatment was reported for pH > 11. Based on the small-scale findings, large-scale field trials were conducted and greater than 3 log removal of E. coli was observed under pH 12 conditions. Therefore, based on the study, off-site lime stabilisation by dosing lime in the range of 10–35% w/w (dry solid basis), depending on the buffer capacity and solids content of the sludge to maintain pH > 11, can be used to sanitise faecal sludge during emergencies, as well as for existing on-site sanitation systems.
A Case Report of Isolated Cuboid Nutcracker Fracture
Authors: Ohmori Takaaki , Katsuo Shinichi , Sunayama Chiaki , Mizuno Katsunori , Ojima Tomohiro , Yamakado Kotaro , Ando Tomonari , Watanabe Shin , Hayashi Seigaku , Tsuchiya Hiroyuki
Published: May 2016

Isolated cuboid fractures are very rare, since they typically occur in combination with midfoot fractures or dislocations. A 61-year-old man presented at our hospital with pain and swelling on the outside of his right foot. The lateral column of his right foot was shortened by approximately 6.5 mm on X-ray. CT showed displacement of the joint surface between the cuboid and the fourth metatarsal, with a 3.5 mm depression. An MRI revealed no other injuries. Based on these findings, we diagnosed the patient with an isolated nutcracker fracture of the cuboid. Using a 1.9 mm arthroscope, we examined the Lisfranc joint. Then the depressed fragments were elevated until the regular joint line was restored. A bone biopsy needle was then used to fill in the large defect with artificial bone. In this case, we did not plate the fracture. Six months after surgery, patient could walk without pain. We report a very rare case of isolated nutcracker fracture of the cuboid. In addition, we suggest our new treatment plan of this fracture.
An Impulsive Three-Species Model with Square Root Functional Response and Mutual Interference of Predator
Authors: Wang Zhen , Shao Yuanfu , Fang Xianjia , Ma Xiangmin
Published: May 2016

An impulsive two-prey and one-predator model with square root functional responses, mutual interference, and integrated pest management is constructed. By using techniques of impulsive perturbations, comparison theorem, and Floquet theory, the existence and global asymptotic stability of prey-eradication periodic solution are investigated. We use some methods and sufficient conditions to prove the permanence of the system which involve multiple Lyapunov functions and differential comparison theorem. Numerical simulations are given to portray the complex behaviors of this system. Finally, we analyze the biological meanings of these results and give some suggestions for feasible control strategies.
Classification of Error-Diffused Halftone Images Based on Spectral Regression Kernel Discriminant Analysis
Authors: Zeng Zhigao , Wen Zhiqiang , Yi Shengqiu , Zeng Sanyou , Zhu Yanhui , Liu Qiang , Tong Qi
Published: May 2016

This paper proposes a novel algorithm to solve the challenging problem of classifying error-diffused halftone images. We firstly design the class feature matrices, after extracting the image patches according to their statistics characteristics, to classify the error-diffused halftone images. Then, the spectral regression kernel discriminant analysis is used for feature dimension reduction. The error-diffused halftone images are finally classified using an idea similar to the nearest centroids classifier. As demonstrated by the experimental results, our method is fast and can achieve a high classification accuracy rate with an added benefit of robustness in tackling noise.
Therapeutic Benefit of Selective Inhibition of p110α PI3-Kinase in Pancreatic Neuroendocrine Tumors
Authors: Soler Adriana , Figueiredo Ana M. , Castel Pau , Martin Laura , Monelli Erika , Angulo-Urarte Ana , Milà-Guasch Maria , Viñals Francesc , Baselga Jose , Casanovas Oriol , Graupera Mariona
Published: May 2016

Purpose: Mutations in the PI3K pathway occur in 16% of patients with pancreatic neuroendocrine tumors (PanNETs), which suggests that these tumors are an exciting setting for PI3K/AKT/mTOR pharmacologic intervention. Everolimus, an mTOR inhibitor, is being used to treat patients with advanced PanNETs. However, resistance to mTOR-targeted therapy is emerging partially due to the loss of mTOR-dependent feedback inhibition of AKT. In contrast, the response to PI3K inhibitors in PanNETs is unknown.

Experimental Design: In the current study, we assessed the frequency of PI3K pathway activation in human PanNETs and in RIP1-Tag2 mice, a preclinical tumor model of PanNETs, and we investigated the therapeutic efficacy of inhibiting PI3K in RIP1-Tag2 mice using a combination of pan (GDC-0941) and p110α-selective (GDC-0326) inhibitors and isoform-specific PI3K kinase-dead–mutant mice.

Results: Human and mouse PanNETs showed enhanced pAKT, pPRAS40, and pS6 positivity compared with normal tissue. Although treatment of RIP1-Tag2 mice with GDC-0941 led to reduced tumor growth with no impact on tumor vessels, the selective inactivation of the p110α PI3K isoform, either genetically or pharmacologically, reduced tumor growth as well as vascular area. Furthermore, GDC-0326 reduced the incidence of liver and lymph node metastasis compared with vehicle-treated mice. We also demonstrated that tumor and stromal cells are implicated in the antitumor activity of GDC-0326 in RIP1-Tag2 tumors.

Conclusions: Our data provide a rationale for p110α-selective intervention in PanNETs and unravel a new function of this kinase in cancer biology through its role in promoting metastasis. Clin Cancer Res; 22(23); 5805–17. ©2016 AACR.
Initial Experience With High-Risk Patients Excluded From Clinical Trials
Authors: Barakat Amr F. , Hussein Ayman A. , Saliba Walid I. , Bassiouny Mohammed , Tarakji Khaldoun , Kanj Mohamed , Jaber Wael , Rodriguez L. Leonardo , Grimm Richard , Hussain M. Shazam , Russman Andrew , Uchino Ken , Wisco Dolora , Rasmussen Peter , Bain Mark , Vargo John , Zuccaro Gregory , Gottesman David , Lindsay Bruce D. , Wazni Oussama M.
Published: May 2016

Background—

The implantation of left atrial appendage closure device (WATCHMAN, Boston Scientific, Natick, MA) is an alternative option to oral anticoagulation (OAC) for stroke prevention in atrial fibrillation. Patients require short-term OAC after implantation to avoid device thrombosis. The 2 clinical trials that assessed this device excluded patients thought not to be candidates for OAC. As such, little is known about the safety of this strategy in patients with previous major bleeding events.

Methods and Results—

All 20 consecutive patients with history of spontaneous major bleeding while on OAC who had subsequently undergone WATCHMAN device implantation at our institution were included. A newly conceived multidisciplinary Atrial Fibrillation Stroke Prevention Center evaluated patients for candidacy for device implantation and subsequent antithrombotic therapy. The primary outcome was spontaneous major bleeding while receiving short-term postprocedural OAC. Median CHA
2
DS
2
-VASc and HAS-BLED scores were 5 (quartiles 5–6) and 5 (quartiles 4–5), respectively. Previous major bleeding events were major gastrointestinal bleeding, intracranial bleeding, spontaneous hemopericardium with cardiac tamponade, and hemarthrosis in 11, 7, 1, and 1 patients, respectively. None of the patients had spontaneous major bleeding during the course of OAC after device implantation. In 1 patient, OAC was discontinued after 40 days because of mechanical fall with head trauma resulting in subdural hematoma with no associated neurological deficits; this was managed conservatively.

Conclusions—

With careful multidisciplinary evaluation, a short course of OAC after WATCHMAN device implantation in patients with previous spontaneous major bleeding events is associated with low risk of recurrent spontaneous major bleeding.
Relationship Between Femoral Vascular Closure Devices and Short-Term Mortality From 271 845 Percutaneous Coronary Intervention Procedures Performed in the United Kingdom Between 2006 and 2011
Authors: Farooq Vasim , Goedhart Dick , Ludman Peter , de Belder Mark A. , Harcombe Alun , El-Omar Magdi
Published: May 2016

Background—

The impact of vascular closure devices (VCDs) via the femoral arterial access site on short-term mortality in patients undergoing percutaneous coronary intervention is currently unknown.

Methods and Results—

The association between femoral arterial vascular access site management (manual pressure [including external clamp] versus VCD) and 30-day mortality was examined in a national real-world registry of 271 845 patients undergoing percutaneous coronary intervention for elective, non–ST-segment–elevation myocardial infarction and ST-segment–elevation myocardial infarction indications in the United Kingdom between 2006 and 2011. Crude and propensity score–corrected analyses were performed using Cox regression, with additional analyses undertaken in clinically relevant subgroups; 40.1% (n=109 001) of subjects were treated with manual pressure and 59.9% (n=162 844) with VCD. Subjects treated with VCD had fewer comorbidities and were less likely to present with ST-segment–elevation myocardial infarction and cardiogenic shock (
P
<0.001). Crude 30-day mortality was lower in the group treated with VCD compared with manual pressure (hazard ratio [HR], 0.58; 95% confidence interval [CI], 0.54–0.61; 1.4% versus 2.4%, log rank
P
<0.0001), findings that were substantially reduced but persisted after propensity score correction (HR, 0.91; 95% CI, 0.86–0.97; 1.8% versus 2.0% versus
P
<0.001). A more pronounced association of VCD with a reduction in 30-day mortality was evident in females (HR, 0.85; 95% CI, 0.77–0.94;
P
interaction
=0.037), presentation with acute coronary syndrome (HR, 0.88; 95% CI, 0.83–0.94;
P
interaction
=0.0027), or recent lysis (HR, 0.63; 95% CI, 0.40–1.01;
P
interaction
=0.0001).

Conclusions—

When compared with manual pressure, VCD was associated with a minor short-term (30-day) prognostic benefit after propensity score correction in the global population and clinically relevant subgroups. The potential for residual confounding factors impacting on short-term mortality cannot be excluded, despite the study having measured and balanced all recorded confounder factors.
Vascular Complications of Diabetes
Authors: Beckman Joshua A. , Creager Mark A.
Published: May 2016

Over the last several decades, the global incidence and prevalence of diabetes mellitus has increased significantly. The raised incidence rate is projected to continue as greater numbers of persons adopt a Western lifestyle and diet. Patients with diabetes mellitus are at heightened risk of both adverse microvascular and cardiovascular events. Moreover, once cardiovascular disease develops, diabetes mellitus exacerbates progression and worsens outcomes. The medical management of patients with diabetes mellitus mandates comprehensive risk factor modification and antiplatelet therapy. Recent clinical trials of new medical therapies continue to inform the care of patients with diabetes mellitus to reduce both cardiovascular morbidity and mortality.
Heart Failure Considerations of Antihyperglycemic Medications for Type 2 Diabetes
Authors: Standl Eberhard , Schnell Oliver , McGuire Darren K.
Published: May 2016

Prevalent and incident heart failure (HF) is increased in people with type 2 diabetes mellitus, with risk directly associated with the severity of hyperglycemia. Furthermore, in patients with type 2 diabetes mellitus, mortality is increased ≈10-fold in patients with versus without HF. Reducing HF with antihyperglycemic therapies, however, has been unsuccessful until recently. In fact, HF as an important outcome in patients with type 2 diabetes mellitus seems to be heterogeneously modulated by antihyperglycemic medications, as evidenced by results from cardiovascular outcome trials (CVOTs) and large observational cohort studies. Appropriately powered and executed CVOTs are necessary to truly evaluate cardiovascular safety and efficacy of new antihyperglycemic medications, as reflected by the guidance of the US Food and Drug Administration and other regulatory agencies since 2008. In light of the best available evidence at present, metformin and the sodium-glucose-co-transporter 2-inhibitor empagliflozin seem to be especially advantageous with regard to HF effects, with their use associated with reduced HF events and improved mortality. Acarbose, the dipeptidyl-peptidase 4-inhibitor sitagliptin, the glucagon-like peptide 1-receptor agonist lixisenatide based on presently available CVOT results comprise reasonable additional options, as significant harm in terms of HF has been excluded for those drugs. Additions to this list are anticipated pending results of ongoing CVOTs. Although no HF harm was seen in CVOTs for insulin or sulfonylureas, they should be used only with caution in patients with HF, given their established high risk for hypoglycemia and some uncertainties on their safety in patients with HF derived from epidemiological observations. Pioglitazone is contraindicated in patients with HF>New York Heart Association I, despite some benefits suggested by CVOT subanalyses.
A Diagram is a Trivial Machine
Authors: Asef Mario
Published: May 2016

I generate diagrams with the purpose of understanding the narratives, form, and aesthetics of sociocultural and political structures. This leaves room for the production of artistic works that can be introduced into the machinery of everyday life. The idea of the diagram emerged almost at the same time as the idea of the machine, although we cannot really tell which existed first. However, it seems clear that both are intrinsically connected. Machines and diagrams can be seen as a representation of a narrative system that leads the process of the creation of knowledge. What they share is essentially narrative: we create machines using diagrammatic narratives, and with those same narratives, we create knowledge. Narratives are the real machines.
From the Stamps to the Bubble
Authors: Amaral Aracy
Published: May 2016

The introductory text foregrounds the article “From the Stamps to the Bubble” (1968) by Brazilian historian and curator Aracy A. Amaral. It seeks to locate the primary document within a broader historiography of Brazilian art in the second half of the 1960s, and examine the ways in which the military dictatorship, along with certain cultural exchanges facilitated by Brazil's economic development in this period affected artistic production. Placing particular attention on the multiple terminologies that were in use when the article was written, the introduction focuses on the contiguities of Pop Art in the Brazilian cultural milieu. It argues that Pop was present inasmuch as it inspired artists to initiate a process of radical experimentation, which empowered them to depart from an avant-garde tradition founded on geometric abstraction.
Reconstructing the development of the aspect marker te ‘to acquire’ in Southwestern Yuè: a missing link between Yuè and Hakka
Authors: Kwok Bit-Chee
Published: May 2016

This paper provides a synchronic description and reconstructs the developmental pathway of the aspect marker te in four Southwestern Yuè dialects of Chinese, located in far western Guǎngdōng. Synchronically, te functions as a perfective aspect marker and a perfect aspect marker (similar to Mandarin Chinese le but different from Cantonese zo). Diachronically, te is believed to have been transferred from the neighboring Hakka dialects through substratum influence. We argue that te is grammaticalized from the verb dé 得 ‘to acquire,’ of the Hakka dialects. This study reveals that the aspectual use of te is an essential part of a missing link between Yuè and Hakka. 

Cet article offre des descriptions synchroniques et reconstruit la voie de développement du marqueur aspectuel te dans quatre dialectes chinois de Yuè du sud-ouest, qui se trouvent à l’extrême-ouest de la province de Guǎngdōng. Synchroniquement, te fonctionne à la fois comme un marquer aspectuel du perfectif et du parfait (comparable à le en chinois mandarin mais différent du zo en cantonais). Diachroniquement, nous pensons que te a été emprunté des dialectes voisins de Hakka, et ainsi subi d’une influence de substrat. Nous argumentons en faveur de l’origine Hakka de te : il est grammaticalisé du verbe dé 得 qui signifie ‘acquérir’ dans les dialectes Hakka. Cette étude révèle que l'usage aspectuel de te joue un rôle essentiel du lien manquant entre les groupes dialectaux de Yuè et Hakka.
Colloquium 2 Commentary on Barney
Authors: Vogt Katja Maria
Published: May 2016

Rachel Barney proposes that Plato’s theory of the tripartite soul is plausibly compared to scientific theories today. I depart from Barney by proposing that the tripartite soul is a model and that its status is hypothetical. And I raise four questions: (1) What follows from the Plato-science comparison, as Barney conceives of it? (2) Which questions emerge if science is looked at in the sophisticated mode that Barney employs in her discussion of Plato? (3) Current science invokes a multitude of subsystems relevant to motivation. Why compare it with tripartition? Stoic psychology may share more fundamental ideas with current science, including the premise that all goings-on in the soul are physiological movements. (4) If tripartition is a model, why would one expect it to account for all dimensions of epistemic activity?
Colloquium 3 Why the Gods Love what is Holy: Euthyphro 10–11
Authors: Kosman Aryeh
Published: May 2016

In Plato’s Euthyphro, an early response to Socrates’ question, What is holiness? defines holiness as what is loved by all the gods. Socrates responds to this proposed definition with an argument that is often misunderstood. English translations, in particular, finding it difficult to represent the argument’s distinction between finite passive constructions—‘x is loved’—and passive participial constructions—‘x is beloved’—represent the argument instead as concerned with a distinction between active and passive constructions. In this essay, I give a correct analysis of the argument, using the relation of ‘x is employed’ and ‘x is an employee’ to illustrate the relation between finite passives and passive participles. Abrams is an employee because she’s employed; it’s not the case that she’s employed because she’s an employee. In the same way, someone is beloved because he’s loved; it’s not that he’s loved because he’s beloved. It’s easy then to see how Plato’s argument follows, and easy to see what Plato intends its limits to reveal.
Ixora ravikumarii, a new name for Ixora monticola Gamble (Rubiaceae: Ixoroideae)
Authors: KOTTAIMUTHU RAMALINGAM
Published: May 2016

Ixora Linnaeus (1753: 110) is the third largest genus of the family Rubiaceae with more than 500 species distributed in tropical and subtropical regions of the world (Mouly et al. 2009). The genus Ixora is easily recognized by its articulate petioles, tetramerous flowers, bilobed stigma, uni-ovulate locules and seeds with a large adaxial hilar cavity (De Block 2008). In India, the genus is represented by 47 species (Barbhuiya et al. 2012; Murugan & Prabhu 2014; Karthigeyan & Arisdason 2015). Among of them, Ixora agasthyamalayana Sivadasan & Mohanan (1991: 313), I. beddomei Husain & Paul (1986: 87), I. gamblei Ramachandran & Nair (1988: 220), I. johnsonii Hooker (1897: 139), I. lawsonii Gamble (1920: 247), I. malabarica (Dennstedt 1818: 37) Mabberley (1977: 539), I. manantoddii Husain & Paul (1991: 16), I. mercaraica Husain & Paul (1986: 88), I. monticola Gamble (1920: 246) and I. sivarajiana Pradeep (1997: 315) are endemic to Western Ghats (Singh et al. 2015). During the verification of Ixora species from the Western Ghats of Tamil Nadu, the author found that the name Ixora monticola Gamble (1920: 246) is an later illegitimate homonym of I. monticola (Hiern 1870: 177) Kuntze (1891: 287). Therefore, a new name, Ixora ravikumarii Kottaim., is proposed here as a replacement name for I. monticola Gamble.
Micromechanical modeling of 8-harness satin weave glass fiber-reinforced composites
Authors: Choudhry RS , Khan Kamran A , Khan Sohaib Z , Khan Muhammad A , Hassan Abid
Published: May 2016

This study introduces a unit cell-based finite element micromechanical model that accounts for correct post cure fabric geometry, in situ material properties and void content within the composite to accurately predict the effective elastic orthotropic properties of 8-harness satin weave glass fiber-reinforced phenolic composites. The micromechanical model utilizes a correct post cure internal architecture of weave, which was obtained through X-ray microtomography tests. Moreover, it utilizes an analytical expression to update the input material properties to account for in situ effects of resin distribution within yarn (the yarn volume fraction) and void content on yarn and matrix properties. This is generally not considered in modeling approaches available in literature and in particular, it has not been demonstrated before for finite element micromechanics models of 8-harness satin weave composites. The unit cell method is used to obtain the effective responses by applying periodic boundary conditions. The outcome of the analysis based on the proposed model is validated through experiments. After validation, the micromechanical model was further utilized to predict the unknown effective properties of the same composite.
Obligation and Impersonality
Authors: Ogien Albert
Published: May 2016

Although sociologists conceive obligation as an objective force (the social) that compels individuals to act and think according to pre-defined norms of conduct and ways of reasoning, philosophers view it as an imperative that is met through the agent’s deliberation. The aim of this article is to undermine the standard dichotomy between the deterministically sociological and the moral–philosophical views of obligation by way of contending that Wittgenstein’s view on blind obedience (as analyzed by Meredith Williams) bears a conception of the social. I will then argue that Wittgenstein’s notion of forms of life and the sociological notion of situation refer to the same encompassing phenomenon: obligation. I will finally claim that this phenomenon should be re-specified in terms of impersonality to devise a shared dynamic conception of obligation admitting that a plurality of contextual normative orders monitor collective and individual action in ordinary life.
Optimal boundary control of a coupled system consisting of Kuramoto–Sivashinsky–Korteweg–de Vries and heat equations
Authors: Sun Bing , Wu Mi-Xia
Published: May 2016

This paper is concerned with the optimal boundary control of a non-dimensional non-linear parabolic system consisting of the Kuramoto–Sivashinsky–Korteweg–de Vries equation and a heat equation. By the Dubovitskii and Milyutin functional analytical approach, first in the fixed final horizon case we prove the Pontryagin maximum principle of the optimal control problem of this coupled system. Then under weaker additional conditions, we study the controlled system in the free final horizon case and present further investigational results of current interests. The necessary optimality conditions are established for optimal control problems in these two cases. Finally, a remark on how to utilize the obtained results is also made for illustration.
OZI: Australian English Communicative Development Inventory
Authors: Kalashnikova Marina , Schwarz Iris-Corinna , Burnham Denis
Published: May 2016

For more than 20 years, the MacArthur–Bates Communicative Development Inventory (CDI) and its adaptations for languages other than English have been used as reliable measures of infants’ and toddlers’ early receptive and productive vocabulary size. This article introduces the OZI, the Australian English adaptation of the MacArthur–Bates CDI, now normed for 12- to 30-month-old children. The findings of two studies are presented: (1) a comparison study that demonstrated that toddlers ( N = 64) acquiring Australian English (24- and 30-month-olds) obtain higher productive vocabulary scores on the OZI than the MacArthur–Bates CDI; and (2) an OZI norming study that included 12- to 30-month-old Australian infants and toddlers ( N = 1496). These studies provide (i) evidence for the greater applicability of the OZI for infants and toddlers learning Australian English and (ii) productive vocabulary acquisition norms for Australian English for ages 12–30 months, a research and diagnostic tool highly anticipated by researchers and clinicians around Australia.
Assessment of serum chemerin, vaspin and omentin-1 levels in patients with polycystic ovary syndrome
Authors: Guvenc Yesim , Var Ahmet , Goker Asli , Kuscu Naci Kemal
Published: May 2016

Objective

To determine serum chemerin, vaspin and omentin-1 in overweight and normal weight patients with polycystic ovary syndrome (PCOS) and investigate the possible relationship between these adipokines and metabolic syndrome.

Methods

This cross sectional study enrolled women with PCOS and healthy women. Serum chemerin, vaspin and omentin-1 were assessed by enzyme-linked immunosorbent assay methods.

Results

Forty patients with PCOS and 30 healthy controls were included in the study. In the PCOS group, 18 women were overweight (body mass index [BMI] = 25.0–29.9 kg/m2) and 22 had normal weight (BMI = 18.5–24.9 kg/m2). Chemerin, total cholesterol, dehydroepiandrosterone sulphate and free androgen index (FAI) were significantly higher; and high-density lipoprotein cholesterol and sex hormone binding globulin were significantly lower in overweight PCOS patients compared with normal weight PCOS patients. A positive correlation was found between chemerin and BMI, triglyceride, insulin, homeostatic model assessment of insulin resistance and FAI in the PCOS group. There was no difference in serum chemerin, vaspin and omentin-1 between PCOS patients and healthy controls.

Conclusion

Circulating chemerin was increased in overweight compared with normal weight PCOS patients. The most predictive variables for circulating chemerin in PCOS patients were BMI, FAI and age.
A Decade of Change: Roper v. Simmons, Defending Childhood, and Juvenile Justice Policy
Authors: Benekos Peter J. , Merlo Alida V.
Published: May 2016

In the last decade, juvenile justice has emerged with more compassion and child-focused policies. During this time, crime decreased, successful strategies for prevention and intervention were identified, neuroscience examined the wiring of the adolescent brain, and the Attorney General established a federal mandate to recognize and respond to children exposed to violence (CEV). In this context, the authors identify two developments that contributed to the ongoing iterations of juvenile justice: Supreme Court decisions that restrict excessive juvenile punishments and policies that recognize the consequences of childhood trauma and the importance of relevant treatment. The Supreme Court rationale in Roper v. Simmons, Graham v. Florida, Miller v. Alabama, and Montgomery v. Louisiana was instrumental in underscoring that youth are different from adults and therefore require different sentencing. The second development was a broader understanding of the scope and consequences of childhood trauma which renewed support to identify and care for youth exposed to violence. The authors review the Court’s rationale in moving policy away from harsh punishment and retribution, the evidence-based support for trauma-informed treatment of youth, and the limits of Court decisions and policy changes in reforming juvenile justice.
Moderators of Theory-Based Interventions to Promote Physical Activity in 77 Randomized Controlled Trials
Authors: Bernard Paquito , Carayol Marion , Gourlan Mathieu , Boiché Julie , Romain Ahmed Jérôme , Bortolon Catherine , Lareyre Olivier , Ninot Gregory
Published: May 2016

A meta-analysis of randomized controlled trials (RCTs) has recently showed that theory-based interventions designed to promote physical activity (PA) significantly increased PA behavior. The objective of the present study was to investigate the moderators of the efficacy of these theory-based interventions. Seventy-seven RCTs evaluating theory-based interventions were systematically identified. Sample, intervention, methodology, and theory implementation characteristics were extracted, coded by three duos of independent investigators, and tested as moderators of interventions effect in a multiple–meta-regression model. Three moderators were negatively associated with the efficacy of theory-based interventions on PA behavior: intervention length (≥14 weeks; β = −.22, p = .004), number of experimental patients (β = −.10, p = .002), and global methodological quality score (β = −.08, p = .04). Our findings suggest that the efficacy of theory-based interventions to promote PA could be overestimated consequently due to methodological weaknesses of RCTs and that interventions shorter than 14 weeks could maximize the increase of PA behavior.
Fibroline: A mobile app for improving the quality of life of young people with fibromyalgia
Authors: de la Vega Rocío , Roset Roman , Galán Santiago , Miró Jordi
Published: May 2016

Fibroline is a mobile application with a self-administered cognitive behavioral treatment for young people with fibromyalgia or chronic widespread pain, designed to reduce pain and other common negative symptoms and improve quality of life. Our aims are to report on the usability and feasibility protocols used to assess the app. Two usability cycles were implemented. A group of patients followed the cognitive behavioral treatment intervention to test its feasibility. Qualitative data were collected and content analyses were conducted. The results demonstrated that the app is error-free, easy to use, liked by the users, and acceptable.