bluuebunny/crossref_metadata_2025_split huggingface dataset:
The HCR-20 Version 3: A Case Study in Risk Formulation
Authors: Logan Caroline 
Published: May 2014

The third edition of the HCR-20 (HCR-20V3, Douglas, Hart, Webster, et al., 2013) consolidates essential recent thinking about risk assessment and management using the structured professional judgement approach. As with the preceding Risk for Sexual Violence Protocol (Hart, Kropp, Laws et al., 2003), risk factors for violence are now assessed for their relevance as well as presence, scenario planning has a central place in anticipating the nature, severity, imminence and likelihood of future harm, and risk management strategies must incorporate a combination of treatment, supervision, monitoring and victim safety planning interventions and recommendations. However, the key process now proposed for linking the assessment and overall management of risk is risk formulation—the act of understanding the underlying mechanism of an individual's harm potential in order to develop sensitive and proportionate hypotheses to facilitate change (embodied within the risk management plan). In this paper, the process of risk formulation is described and illustrated with a case study—Paul. A brief report of the risk assessment, formulation and management recommendations for Paul illustrate the key features of what is recommended in the new version of this internationally renowned violence risk guide. However, empirical research into risk formulation remains outstanding.
Geology, tectonics and topography underlined by L'Aquila earthquake TIR precursors
Authors: Piroddi Luca , Ranieri Gaetano , Freund Friedemann , Trogu Antonio 
Published: May 2014

Abstract
Anomalous thermal infrared (TIR) emissions have widely been detected by satellite sensors before the major earthquakes. A recent processing technique for geostationary thermal data, developed for the case of the 2009 April 6, magnitude 6.3 L'Aquila earthquake, makes it possible to identify areas of enhanced TIR emissions around the epicentral region at a mean distance of less than 50 km but inside a radius of about 100 km. The index, called Night Thermal Gradient (NTG), derived from 4-D time-series data (two spatial and two temporal coordinates), identifies TIR anomalies by following the temperature trend during night, when the surface of the Earth is expected to cool. Leading up to the L'Aquila earthquake, an anomalous warming trend was observed. In this study, the anomalous NTG pattern is compared to the expected normal trend, taking into account the seismogenic faults, the overall tectonic setting, lithological spatial features, the orography and world stress map near the epicentral region. Main results are that a certain lithological selectivity can be recognized and that the known main stress field and seismogenic faults seem to be less important than certain tectonic lineaments, which are classified as non-seismogenic. The strong correlation between the topography and the TIR anomalies is in agreement with proposed physical mechanism for the generation of TIR anomalies. This relation is, in turn, present mainly in correspondence to two tectonic lineaments which in particular are thrusts: therefore, strong compressive states seem to be a positive condition for the generation of TIR anomalies. The temporary modification of these stress fields have triggered the Paganica Fault to its normal rupture mechanism. It is important to note that the distances, over which the TIR anomalies occurred, are an order of magnitude larger than the estimated length of the main fault rupture. Pixel-by-pixel time-series comparisons between the maximum TIR anomaly area and the epicentre of the main shock show that the increase in radiative emission occurred in the areas of maximum TIR anomalies and did not start by spreading outward from the epicentral region.
Costly sexual dimorphism in Cyclommatus metallifer stag beetles
Authors: Goyens Jana , Dirckx Joris , Aerts Peter 
Published: May 2014

Summary

In many animal species, male armature has evolved through sexual selection. This male weaponry can increase reproductive success, but only if the owner overcomes the associated costs.

Male stag beetles bear one of the most extreme examples of male weaponry: their mandibles can be almost as long as their own body. We question whether the armature of male Cyclommatus metallifer negatively affects terrestrial locomotion (stability and cost). If so, we investigate whether these effects are potentially compensated by morphological and/or behavioural features, as seen in other specialized insect species. Conspecific females are used to represent the non‐dimorphed condition.

The presence of the huge male mandibular apparatus shifts the body centre of mass (bCOM) anteriorly. Concomitantly, the male fore limbs are 28% longer and are systematically positioned in a more anterior angular sector than in females. Thus, the rostral border of the support area of the leg tripod also moves forward. This suggests a stability enhancing mechanism. However, in contrast to load‐carrying ants, the anteriorly placed bCOM still creates two pronounced statically instable periods each locomotor cycle.

Due to the static instability, males must adjust their locomotor behaviour: they walk at higher cycle frequencies when compared to females of the same size, to ensure they proceed to the next stance before bumping to the ground with their heavy heads.

Contrary to other specialized load‐carrying insect species, the (muscle) mass specific mechanical cost of transport of males exceeds that of females by 40%.

Since neither stability nor cost of transport benefit from the male forelimb size and positioning, their role in guaranteeing adequate terrestrial locomotion while carrying an enlarged mandibular apparatus seems doubtful. Instead, the long limbs are themselves functional in fights, by pitching the body upwards in order to throw opponents backwards.

The oversized male stag beetle armature comes at high ecological costs: locomotion economics as well as stability clearly suffer from the large mandibles. The observed limb length dimorphism does not prevent this, but should probably be considered part of sexual selection, rather than a compensation for its consequences.
The Class Characteristic Mark of the H&M Mul‐T‐Lock Picking Tool in Toolmarks Examination
Authors: Volkov Nikolai , Finkelstein Nir , Novoselsky Yehuda , Tsach Tsadok 
Published: May 2014

AbstractMul‐T‐Lock is a high security lock cylinder distinguished by the use of a telescoping “pin‐in‐pin”—tumbler design. Picking the Mul‐T‐Lock cylinder with a traditional picking tool is highly complicated because it can get stuck between the inner and outer pins. The H&M Mul‐T‐Lock picking tool was designed to overcome this problem and facilitate the picking of the “pin‐in‐pin” cylinder. The purpose of this research is to determine whether H&M Mul‐T‐Lock picking tool leaves class characteristic mark and whether it can be distinguished from traditional picking tools marks and from regular key marks. It also describes and determines the class characteristic mark left on telescopic pins, its origin, recurrence, and its benefit to the toolmarks examiner. When receiving a Mul‐T‐Lock from a crime scene, a toolmarks examiner can quickly determine whether or not it was picked by an H&M Mul‐T‐Lock picking tool by noticing the class characteristic mark which this typical tool leaves.
Proposed diagnostic algorithm for patients with suspected mastocytosis: a proposal of the European Competence Network on Mastocytosis
Authors: Valent P. , Escribano L. , Broesby‐Olsen S. , Hartmann K. , Grattan C. , Brockow K. , Niedoszytko M. , Nedoszytko B. , Oude Elberink J. N. G. , Kristensen T. , Butterfield J. H. , Triggiani M. , Alvarez‐Twose I. , Reiter A. , Sperr W. R. , Sotlar K. , Yavuz S. , Kluin‐Nelemans H. C. , Hermine O. , Radia D. , van Doormaal J. J. , Gotlib J. , Orfao A. , Siebenhaar F. , Schwartz L. B. , Castells M. , Maurer M. , Horny H.‐P. , Akin C. , Metcalfe D. D. , Arock M. 
Published: May 2014

AbstractMastocytosis is an emerging differential diagnosis in patients with more or less specific mediator‐related symptoms. In some of these patients, typical skin lesions are found and the diagnosis of mastocytosis can be established. In other cases, however, skin lesions are absent, which represents a diagnostic challenge. In the light of this unmet need, we developed a diagnostic algorithm for patients with suspected mastocytosis. In adult patients with typical lesions of mastocytosis in the skin, a bone marrow (BM) biopsy should be considered, regardless of the basal serum tryptase concentration. In adults without skin lesions who suffer from mediator‐related or other typical symptoms, the basal tryptase level is an important parameter. In those with a slightly increased tryptase level, additional investigations, including a sensitive KIT mutation analysis of blood leucocytes or measurement of urinary histamine metabolites, may be helpful. In adult patients in whom (i) KIT D816V is detected and/or (ii) the basal serum tryptase level is clearly increased (>25–30 ng/ml) and/or (iii) other clinical or laboratory features suggest the presence of ‘occult’ mastocytosis or another haematologic neoplasm, a BM investigation is recommended. In the absence of KIT D816V and other signs or symptoms of mastocytosis or another haematopoietic disease, no BM investigation is required, but the clinical course and tryptase levels are monitored in the follow‐up. In paediatric patients, a BM investigation is usually not required, even if the tryptase level is increased. Although validation is required, it can be expected that the algorithm proposed herein will facilitate the management of patients with suspected mastocytosis and help avoid unnecessary referrals and investigations.
The impact of a history of childhood nocturnal enuresis on adult nocturia and urgency
Authors: Akashi Shunji , Tomita Kazue 
Published: May 2014

AbstractAimThis study examined the association between a childhood history of nocturnal enuresis and nocturia and urgency as an adult.MethodsA questionnaire was completed by 3649 parents and grandparents of children with nocturnal enuresis. The age range of the respondents was 30–89, and 54% were female. The questionnaire included the respondent's age, underlying disease, the age at which nocturnal enuresis was resolved and any current nocturia and urgency.ResultsThe responses enabled us to analyse the risk factors for nocturia and urgency for the total sample, the history of nocturnal eneurisis for 2555 adults aged from 30 to 79 years and the age when nocturnal enuresis resolved for 1300 adults aged from 30 to 49 years. Respondents were significantly more likely to have nocturia and urgency as adults if they had a history of nocturnal enuresis and were aged ≥12 years when their nocturnal enuresis resolved.ConclusionsA childhood history of nocturnal enuresis, particularly nocturnal enuresis that resolved at ≥12 years old, was associated with an increased frequency of adult nocturia and urgency. The impact of previous nocturnal enuresis on adult nocturia and urgency presents a risk that is comparable to ageing and prostatic disease.
Arctigenin Promotes Apoptosis in Ovarian Cancer Cells via the iNOS/NO/STAT3/Survivin Signalling
Authors: Huang Ke , Li Li‐an , Meng Yuan‐guang , You Yan‐qin , Fu Xiao‐yu , Song Lei 
Published: May 2014

AbstractArctigenin is a biologically active lignan extracted from the seeds of Arctium lappa and shows anticancer activity against a variety of human cancers. The aim of this study was to determine the effects of arctigenin on ovarian cancer cell proliferation and survival and associated molecular mechanisms. Human ovarian cancer OVCAR3 and SKOV3 cells were treated with arctigenin, and cell proliferation and apoptosis were assessed. Western blot analysis was used to examine signal transducer and activator of transcription‐3 (STAT3) phosphorylation and survivin and inducible nitric oxide synthase (iNOS) expression. The involvement of STAT3/survivin/iNOS/NO signalling in arctigenin action was checked. Arctigenin treatment resulted in a significant and dose‐dependent inhibition of cell proliferation. Arctigenin‐treated cells showed a 4–6 times increase in the percentage of apoptosis, compared with control cells. Pre‐treatment with Ac‐DEVD‐CHO, a specific inhibitor of caspase‐3, counteracted the induction of apoptosis by arctigenin. Arctigenin treatment significantly inhibited STAT3 phosphorylation and survivin and iNOS expression. Arctigenin‐induced apoptosis was impaired by pre‐transfection with survivin‐expressing plasmid or addition of chemical nitric oxide (NO) donors. Additionally, exogenous NO prevented the suppression of STAT3 phosphorylation and survivin expression by arctigenin. Arctigenin treatment inhibits the proliferation and induces caspase‐3‐dependent apoptosis of ovarian cancer cells. Suppression of iNOS/NO/STAT3/survivin signalling is causally linked to the anticancer activity of arctigenin. Therefore, arctigenin may be applicable to anticancer therapy for ovarian cancer.
Time now toTORCtheTORC? New developments in mTORpathway inhibition in lymphoid malignancies
Authors: Eyre Toby A. , Collins Graham P. , Goldstone Anthony H. , Cwynarski Kate 
Published: May 2014

SummarySince the discovery of rapamycin in Easter Island soil in 1975, more has been learnt about the relevance and importance of the mammalian target of rapamycin (mTOR) pathway in cell signalling, proliferation and ultimately tumourigenesis. Rapamycin targets the mTORC1 complex alone. Despite initial excitement, rapamycin and its analogues, everolimus and temsirolimus, have displayed limited efficacy in the treatment of lymphoid malignancies. This review highlights the important and well‐described aspects of the critical phosphatidylinositol‐4,5‐bisphosphate 3‐kinase (PI3K)/AKT/mTORpathway and discusses the mechanisms of action of rapamycin, its clinical efficacy in lymphoid malignancies, and the mechanisms of resistance. Renewed interest in targeting the pathway has evolved through the discovery of mTORC2, a protein complex associated with a key mechanism of resistance to first generation mTOR inhibitors. As such, novel dual inhibitors of mTORC1 andmTORC2 have been developed, along with other dual inhibitors of the mTORpathway. The evolution in the development of dual inhibitors is described herein, along with the burgeoningin vitro, pre‐clinical data and the early phase clinical data available. Although historically mTORinhibitors have been used extensively in haematopoietic and solid organ transplant prophylaxis, this review will focus on developments of their use in lymphoid malignancies.
Combined injection of three different lineages of early‐differentiating human amniotic fluid‐derived cells restores urethral sphincter function in urinary incontinence
Authors: Chun So Young , Kwon Joon Beom , Chae Seon Yeong , Lee Jong Kil , Bae Jae‐sung , Kim Bum Soo , Kim Hyun Tae , Yoo Eun Sang , Lim Jeong Ok , Yoo James J , Kim Wun‐Jae , Kim Bup Wan , Kwon Tae Gyun 
Published: May 2014

ObjectiveTo investigate whether a triple combination of early‐differentiated cells derived from human amniotic fluid stem cells (hAFSCs) would show synergistic effects in urethral sphincter regeneration.Materials and MethodsWe early‐differentiated hAFSCs into muscle, neuron and endothelial progenitor cells and then injected them into the urethral sphincter region of pudendal neurectomized ICR mice, as single‐cell, double‐cell or triple‐cell combinations. Urodynamic studies and histological, immunohistochemical and molecular analyses were performed.ResultsUrodynamic study showed significantly improved leak point pressure in the triple‐cell‐combination group compared with the single‐cell‐ or double‐cell‐combination groups. These functional results were confirmed by histological and immunohistochemical analyses, as evidenced by the formation of new striated muscle fibres and neuromuscular junctions at the cell injection site. Molecular analysis showed higher target marker expression in the retrieved urethral tissue of the triple‐cell‐combination group. The injection of early‐differentiated hAFSCs suppressed in vivo host CD8 lymphocyte aggregations and did not form teratoma. The nanoparticle‐labelled early‐differentiated hAFSCs could be tracked in vivo with optical imaging for up to 14 days after injection.ConclusionOur novel concept of triple‐combined early‐differentiated cell therapy for the damaged sphincter may provide a viable option for incontinence treatment.
Inhibitory role of phosphatidylinositol 4,5‐bisphosphate on TMEM16A‐encoded calcium‐activated chloride channels in rat pulmonary artery
Authors: Pritchard H A T , Leblanc N , Albert A P , Greenwood I A 
Published: May 2014

Background and PurposeCalcium‐activated chloride channels (CaCCs) are key depolarizing mechanisms that have an important role in vascular smooth muscle contraction. Here, we investigated whether these channels are regulated by phosphatidylinositol (4,5) bisphosphate [P(4,5)P2], a known regulator of various ion channels.Experimental ApproachCalcium‐activated Cl− currents (IClCa) were recorded by patch clamp electrophysiology of rat isolated pulmonary artery smooth muscle cells. TMEM16A protein‐phosphoinositide interaction was studied by co‐immunoprecipitation and phosphoinositide binding arrays on protein lysates from whole pulmonary arteries and HEK293 cells overexpressing TMEM16A, the molecular correlate.Key ResultsPI(4,5)P2 and other phospholipids were shown to bind directly to TMEM16A isolated from whole pulmonary artery (PA) and TMEM16A‐eGFP expressed in HEK293 cells. Agents that reduced PI(4,5)P2 levels through different routes [PLC activation, PI4K inhibition, PI(4,5)P2 scavenging and absorption] all increased IClCa evoked by solutions containing clamped‐free [Ca2+], whereas enrichment of activating solutions with PI(4,5)P2 inhibited IClca in PA smooth muscle cells with approximately 50% reduction at 1 μM.Conclusions and ImplicationsThese data are the first to show a negative regulation of TMEM16A‐encoded CaCCs by PI(4,5)P2 and propose that control of PI(4,5)P2 levels is a key determinant of arterial physiology.
Preclinical antitumor activity of S‐222611, an oral reversible tyrosine kinase inhibitor of epidermal growth factor receptor and human epidermal growth factor receptor 2
Authors: Tanaka Hidekazu , Hirata Michinari , Shinonome Satomi , Wada Toru , Iguchi Motofumi , Dohi Keiji , Inoue Makiko , Ishioka Yukichi , Hojo Kanji , Yamada Tomomi , Sugimoto Tatsuya , Masuno Koichi , Nezasa Ken‐ichi , Sato Norihito , Matsuo Kenji , Yonezawa Shuji , Frenkel Eugene P. , Shichijo Michitaka 
Published: May 2014

Epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2) are validated molecular targets in cancer therapy. Dual blockade has been explored and one such agent, lapatinib, is in clinical practice but with modest activity. Through chemical screening, we discovered a novel EGFR and HER2 inhibitor, S‐222611, that selectively inhibited both kinases with IC50s below 10 nmol/L. S‐222611 also inhibited intracellular kinase activity and the growth of EGFR‐expressing and HER2‐expressing cancer cells. In addition, S‐222611 showed potent antitumor activity over lapatinib in a variety of xenograft models. In evaluations with two patient‐oriented models, the intrafemoral implantation model and the intracranial implantation model, S‐222611 exhibited excellent activity and could be effective against bone and brain metastasis. Compared to neratinib and afatinib, irreversible EGFR/HER2 inhibitors, S‐222611 showed equivalent or slightly weaker antitumor activity but a safer profile. These results indicated that S‐222611 is a potent EGFR and HER2 inhibitor with substantially better antitumor activity than lapatinib at clinically relevant doses. Considering the safer profile than for irreversible inhibitors, S‐222611 could be an important option in future cancer therapy.
Enhanced anti‐angiogenic effect of E7820 in combination with erlotinib in epidermal growth factor receptor–tyrosine kinase inhibitor‐resistant non‐small‐cell lung cancer xenograft models
Authors: Ito Ken , Semba Taro , Uenaka Toshimitsu , Wakabayashi Toshiaki , Asada Makoto , Funahashi Yasuhiro 
Published: May 2014

Most non‐small‐cell lung cancers (NSCLCs) harboring activating mutations in the epidermal growth factor receptor (EGFR) are initially responsive to EGFR tyrosine kinase inhibitors (EGFR‐TKIs); however, they invariably develop resistance to these drugs. E7820 is an angiogenesis inhibitor that decreases integrin‐α2 expression and is currently undergoing clinical trials. We investigated whether E7820 in combination with erlotinib, an EGFR‐TKI, could overcome EGFR‐TKI‐resistance in the NSCLC cell lines A549 (KRAS; G12S), H1975 (EGFR; L858R/T790M), and H1650 (PTEN; loss, EGFR; exon 19 deletion), which are resistant to erlotinib. Immunohistochemical analysis was carried out in xenografted tumors to investigate anti‐angiogenesis activity and endothelial cell apoptosis levels by endothelial cell marker CD31 and TUNEL staining, respectively. Treatment with E7820 (50 mg/kg) with erlotinib (60 mg/kg) showed a synergistic antitumor effect in three xenograft models. Immunohistochemical analysis indicated that combined treatment with E7820 and erlotinib significantly decreased microvessel density and increased apoptosis of tumor‐associated endothelial cells compared with use of only one of the agents. This combination increased apoptosis in HUVECs through activation of both intrinsic and extrinsic apoptosis pathways in vitro. The combination of E7820 with erlotinib is an alternative strategy to overcome erlotinib resistance in NSCLC by enhancement of the anti‐angiogenic activity of E7820.
Identifying subgroups of obesity using the product of triglycerides and glucose: the Korea National Health and Nutrition Examination Survey, 2008–2010
Authors: Lee Seung‐Hwan , Han Kyungdo , Yang Hae Kyung , Kim Mee Kyoung , Yoon Kun‐Ho , Kwon Hyuk‐Sang , Park Yong‐Moon 
Published: May 2014

SummaryObjectiveTo determine whether the TyG index, a product of the levels of triglycerides and glucose, may be a valuable marker for identifying metabolically obese but normal weight (MONW) or metabolically healthy but obese (MHO) individuals.Design and subjectsA total of 17 029 nondiabetic subjects (7185 men and 9844 women) were selected from the Korea National Health and Nutrition Examination Survey conducted in 2008–2010. Individuals with a normal body mass index (BMI) (≥18·5 and <23 kg/m2) and the highest quartile of the homoeostasis model assessment of insulin resistance (HOMA‐IR) were classified as MONW. Individuals with obesity (BMI ≥25 kg/m2) and the lowest quartile of HOMA‐IR were classified as MHO.MeasurementsThe TyG index was calculated as ln[fasting triglycerides (mg/dl) × fasting glucose (mg/dl)/2].ResultsThe levels of the TyG index paralleled with various metabolic risk parameters. The index was significantly higher in the MONW group and lower in the MHO group when compared with the non‐MONW group and the non‐MHO group, respectively. The odds ratios (ORs) of being categorized into the MONW group were approximately fourfold higher in the highest vs lowest quartiles of the TyG index (3·999: 95% CI, 2·508–6·376 in men; 4·737: 95% CI, 3·418–6·565 in women) among normal weight subjects. Conversely, there was a stepwise decrease in the OR of being categorized into the MHO group across the TyG index quartiles among obese subjects.ConclusionsThese data highlight the value of the TyG index in discriminating those subjects with higher risks of metabolic diseases.