bluuebunny/crossref_metadata_2025 huggingface dataset:
Systematic review of surgical and medical treatment for tertiary hyperparathyroidism
Authors: Dulfer R R , Franssen G J H , Hesselink D A , Hoorn E J , van Eijck C H J , van Ginhoven T M
Published: May 2017

Background

A significant proportion of patients with chronic kidney disease and secondary hyperparathyroidism (HPT) remain hyperparathyroid after kidney transplantation, a state known as tertiary HPT. Without treatment, tertiary HPT can lead to diminished kidney allograft and patient survival. Parathyroidectomy was commonly performed to treat tertiary HPT until the introduction of the calcimimetic drug, cinacalcet. It is not known whether surgery or medical treatment is superior for tertiary HPT.

Methods

A systematic review was performed and medical literature databases were searched for studies on the treatment of tertiary HPT that were published after the approval of cinacalcet.

Results

A total of 1669 articles were identified, of which 47 were included in the review. Following subtotal and total parathyroidectomy, initial cure rates were 98·7 and 100 per cent respectively, but in 7·6 and 4 per cent of patients tertiary HPT recurred. After treatment with cinacalcet, 80·8 per cent of the patients achieved normocalcaemia. Owing to side-effects, 6·4 per cent of patients discontinued cinacalcet treatment. The literature regarding graft function and survival is limited; however, renal graft survival after surgical treatment appears comparable to that obtained with cinacalcet therapy.

Conclusion

Side-effects and complications of both treatment modalities were mild and occurred in a minority of patients. Surgical treatment for tertiary HPT has higher cure rates than medical therapy.
Pseudomorphic Transformation of Porous Glasses into Micelle‐Templated Silica
Authors: Uhlig Hans , Hollenbach Julia , Rogaczewski Matthias , Matysik Jörg , Brieler Felix J. , Fröba Michael , Enke Dirk
Published: May 2017

Micelle‐templated silica (MTS)‐composites with flexible macroscopic shape, monomodal or bimodal (hierarchical) pore structure, and high mechanical stability can be prepared by partial or complete pseudomorphic transformation of porous glasses (PG). The state of research concerning synthesis, transformation mechanism, characterization, and application of MTS/PG‐composites is reviewed and the investigation of the transformation products by 129Xe NMR spectroscopy and the direct synthesis of Al‐MCM‐41/PG‐composites are introduced. Finally, several approaches like a double‐templating strategy for pore protection is shown.
Aspirin and the risk of cardiovascular events in atherosclerosis patients with and without prior ischemic events
Authors: Bavry Anthony A. , Elgendy Islam Y. , Elbez Yedid , Mahmoud Ahmed N. , Sorbets Emmanuel , Steg Philippe Gabriel , Bhatt Deepak L. ,   for the REACH Registry Investigators
Published: May 2017

Background

The benefit of aspirin among patients with stable atherosclerosis without a prior ischemic event is not well defined.

Hypothesis

Aspirin would be of benefit in outpatients with atherosclerosis with prior ischemic events, but not in those without ischemic events.

Methods

Subjects from the Reduction of Atherothrombosis for Continued Health registry were divided according to prior ischemic event (n =21 724) vs stable atherosclerosis, but no prior ischemic event (n = 11 872). Analyses were propensity score matched. Aspirin use was updated at each clinic visit and considered as a time‐varying covariate. The primary outcome was the first occurrence of cardiovascular death, myocardial infarction, or stroke.

Results

In the group with a prior ischemic event, aspirin use was associated with a marginally lower risk of the primary outcome at a median of 41 months (hazard ratio [HR]: 0.81, 95% confidence interval [CI]: 0.65‐1.01, P = 0.06). In the group without a prior ischemic event, aspirin use was not associated with a lower risk of the primary outcome at a median of 36 months (HR: 1.03, 95% CI: 0.73‐1.45, P = 0.86).

Conclusions

In this observational analysis of outpatients with stable atherosclerosis, aspirin was marginally beneficial among patients with a prior ischemic event; however, there was no apparent benefit among those with no prior ischemic event.
Insight Into the CO2 Capturer Derived From Graphene/MgO Composite
Authors: Dong Xin Yu Ming , Li Yan Yan , Li Shuo Hao , Wang Ying , Zhu Jian Hua
Published: May 2017

Graphene/MgO composite was studied to develop warm CO2 capturer. The structure of doped MgO was examined with XRD and nitrogen adsorption‐desorption, and its basicity was assessed with instantaneous adsorption and temperature programmed desorption (TPD) of CO2. The surface area of MgO was increased ten times by adding graphene, and the CO2 adsorption capability was also significantly enhanced. A new method combined CO2 instantaneous adsorption and TPD technique is proposed here to examine the adsorptive sites of the MgO sorbent, exploring the property‐function relation of the CO2 capturer.
Versatile Reducing Reaction Field within Layered Polysilane for Efficient One‐Pot Synthesis of Metal Nanoparticles
Authors: Ohashi Masataka , Yaokawa Ritsuko , Takatani Yasuhiro , Nakano Hideyuki
Published: May 2017

Metal nanoparticles (MNPs) have received a great deal of attention in both scientific and industrial fields because of their special characteristics originating in the nanostructure. Herein, we developed a new synthesis strategy for MNPs based on the utilization of layered polysilane (Si6H6). The special arrangements of layers in this material allows the formation of an interlayer space with both suitable dimensions and surface chemistry characteristics for reducing metal ions to MNPs in a simple and efficient manner. The interlayer space assimilates a metal ion by a capillary condensation effect. These metal ions are subsequently reduced by the hydrosilyl groups on layered polysilane, thereby forming MNPs within the interlayer space. The synthesis strategies for MNPs presented in this paper can be utilized as a method for recovering and absorbing noble or toxic metal elements.
Quantum theory of the dissipative Josephson parametric amplifier
Authors: Kaiser W. , Haider M. , Russer J. A. , Russer P. , Jirauschek C.
Published: May 2017

Recent research in superconducting quantum circuits operating close to the quantum limit results in the need of a quantum mechanical treatment of losses. Of special interest is the dynamic behaviour of an open quantum system. As an example, a negative‐resistance Josephson parametric amplifier is treated. The DC bias voltage is chosen such that a strong interaction between the Josephson junction and the two resonant circuits, the signal and the idler circuit, is achieved. Power exchange occurs between the two considered resonator modes and also between the resonator modes and the DC power supply. Losses in the resonators are modeled by the quantum Langevin method, which describes the losses by coupling the resonators to a heat bath representing a photon gas in thermal equilibrium. The derived dynamic behaviour does not provide signal energy saturation, like classically expected for parametric amplifiers. Introducing a phenomenological multi‐photon coupling approach, saturation of the amplified signal is ensured. The time evolution of the signal and noise energy is calculated and numerically evaluated for a specific example in cases of both, the quantum Langevin method with and without the phenomenological multi‐photon coupling approach. Copyright © 2017 John Wiley & Sons, Ltd.
Species traits and interaction rules shape a species‐rich seed‐dispersal interaction network
Authors: Sebastián‐González Esther , Pires Mathias M. , Donatti Camila I. , Guimarães Paulo R. , Dirzo Rodolfo
Published: May 2017

Species phenotypic traits affect the interaction patterns and the organization of seed‐dispersal interaction networks. Understanding the relationship between species characteristics and network structure help us understand the assembly of natural communities and how communities function. Here, we examine how species traits may affect the rules leading to patterns of interaction among plants and fruit‐eating vertebrates. We study a species‐rich seed‐dispersal system using a model selection approach to examine whether the rules underlying network structure are driven by constraints in fruit resource exploitation, by preferential consumption of fruits by the frugivores, or by a combination of both. We performed analyses for the whole system and for bird and mammal assemblages separately, and identified the animal and plant characteristics shaping interaction rules. The structure of the analyzed interaction network was better explained by constraints in resource exploitation in the case of birds and by preferential consumption of fruits with specific traits for mammals. These contrasting results when looking at bird–plant and mammal–plant interactions suggest that the same type of interaction is organized by different processes depending on the assemblage we focus on. Size‐related restrictions of the interacting species (both for mammals and birds) were the most important factors driving the interaction rules. Our results suggest that the structure of seed‐dispersal interaction networks can be explained using species traits and interaction rules related to simple ecological mechanisms.
Exercise training in Diastolic Heart Failure (Ex‐DHF): rationale and design of a multicentre, prospective, randomized, controlled, parallel group trial
Authors: Edelmann Frank , Bobenko Anna , Gelbrich Götz , Hasenfuss Gerd , Herrmann‐Lingen Christoph , Duvinage André , Schwarz Silja , Mende Meinhard , Prettin Christiane , Trippel Tobias , Lindhorst Ruhdja , Morris Daniel , Pieske‐Kraigher Elisabeth , Nolte Kathleen , Düngen Hans‐Dirk , Wachter Rolf , Halle Martin , Pieske Burkert
Published: May 2017

Heart failure with preserved ejection fraction (HFpEF) is a common disease with high incidence and increasing prevalence. Patients suffer from functional limitation, poor health‐related quality of life, and reduced prognosis. A pilot study in a smaller group of HFpEF patients showed that structured, supervised exercise training (ET) improves maximal exercise capacity, diastolic function, and physical quality of life. However, the long‐term effects of ET on patient‐related outcomes remain unclear in HFpEF. The primary objective of the Exercise training in Diastolic Heart Failure (Ex‐DHF) trial is to investigate whether a 12 month supervised ET can improve a clinically meaningful composite outcome score in HFpEF patients. Components of the outcome score are all‐cause mortality, hospitalizations, NYHA functional class, global self‐rated health, maximal exercise capacity, and diastolic function. After undergoing baseline assessments to determine whether ET can be performed safely, 320 patients at 11 trial sites with stable HFpEF are randomized 1:1 to supervised ET in addition to usual care or to usual care alone. Patients randomized to ET perform supervised endurance/resistance ET (3 times/week at a certified training centre) for 12 months. At baseline and during follow‐up, anthropometry, echocardiography, cardiopulmonary exercise testing, and health‐related quality of life evaluation are performed. Blood samples are collected to examine various biomarkers. Overall physical activity, training sessions, and adherence are monitored and documented throughout the study using patient diaries, heart rate monitors, and accelerometers. The Ex‐DHF trial is the first multicentre trial to assess the long‐term effects of a supervised ET programme on different outcome measures in patients with HFpEF.
Dealing at Arm's Length: Catalysis with N‐Heterocyclic Carbene Ligands Bearing Anionic Tethers
Authors: Pape Felix , Teichert Johannes F.
Published: May 2017

The catalytic transformations enabled by bidentate N‐heterocyclic carbenes bearing anionic substituents (tethered NHCs) are presented. The use of tethered NHCs as a ligand class for transition‐metal‐catalyzed reactions and their employment in organocatalytic and Lewis‐base‐catalyzed processes is discussed, with a focus on the influence of the anionic tether on the catalyzed reactions of interest.
Influence of zinc borate on flame retardant and thermal properties of polyurethane elastomer composites containing huntite‐hydromagnesite mineral
Authors: Dike Ali Sinan , Tayfun Umit , Dogan Mehmet
Published: May 2017

The effect of zinc borate (ZnB) was studied on the flame retardant and thermal properties of thermoplastic polyurethane containing huntite‐hydromagnesite. The flame retardant properties of thermoplastic polyurethane–based composites were investigated using limiting oxygen index, vertical burning test (UL 94), thermogravimetric analysis, and mass loss calorimeter. No remarkable effect of ZnB was observed on the flammability properties of composites. UL 94 rating did not change regardless of the added amount of ZnB, and the slight increase in limiting oxygen index value was observed at ratio of 1:1. The adjuvant effect of ZnB was observed during the mass loss calorimeter studies by increasing the barrier effect of the residue in the condensed phase and by increasing the formation of incombustible gasses in the gas phase. The highest fire performance was achieved at ratio of 1:1.
Large‐scale computational models of liver metabolism: How far from the clinics?
Authors: Cvitanović Tanja , Reichert Matthias C. , Moškon Miha , Mraz Miha , Lammert Frank , Rozman Damjana
Published: May 2017

Understanding the dynamics of human liver metabolism is fundamental for effective diagnosis and treatment of liver diseases. This knowledge can be obtained with systems biology/medicine approaches that account for the complexity of hepatic responses and their systemic consequences in other organs. Computational modeling can reveal hidden principles of the system by classification of individual components, analyzing their interactions and simulating the effects that are difficult to investigate experimentally. Herein, we review the state‐of‐the‐art computational models that describe liver dynamics from metabolic, gene regulatory, and signal transduction perspectives. We focus especially on large‐scale liver models described either by genome scale metabolic networks or an object‐oriented approach. We also discuss the benefits and limitations of each modeling approach and their value for clinical applications in diagnosis, therapy, and prevention of liver diseases as well as precision medicine in hepatology. (Hepatology 2017;66:1323‐1334).
Targeting CCl4‐induced liver fibrosis by RNA interference–mediated inhibition of cyclin E1 in mice
Authors: Bangen Jörg‐Martin , Hammerich Linda , Sonntag Roland , Baues Maike , Haas Ute , Lambertz Daniela , Longerich Thomas , Lammers Twan , Tacke Frank , Trautwein Christian , Liedtke Christian
Published: May 2017

Initiation and progression of liver fibrosis requires proliferation and activation of resting hepatic stellate cells (HSCs). Cyclin E1 (CcnE1) is the regulatory subunit of the cyclin‐dependent kinase 2 (Cdk2) and controls cell cycle re‐entry. We have recently shown that genetic inactivation of CcnE1 prevents activation, proliferation, and survival of HSCs and protects from liver fibrogenesis. The aim of the present study was to translate these findings into preclinical applications using an RNA interference (RNAi)‐based approach. CcnE1‐siRNA (small interfering RNA) efficiently inhibited CcnE1 gene expression in murine and human HSC cell lines and in primary HSCs, resulting in diminished proliferation and increased cell death. In C57BL/6 wild‐type (WT) mice, delivery of stabilized siRNA using a liposome‐based carrier targeted approximately 95% of HSCs, 70% of hepatocytes, and 40% of CD45+ cells after single injection. Acute CCl4‐mediated liver injury in WT mice induced endogenous CcnE1 expression and proliferation of surviving hepatocytes and nonparenchymal cells, including CD45+ leukocytes. Pretreatment with CcnE1‐siRNA reverted CcnE1 induction to baseline levels of healthy mice, which was associated with reduced liver injury, diminished proliferation of hepatocytes and leukocytes, and attenuated overall inflammatory response. For induction of liver fibrosis, WT mice were challenged with CCl4 for 4‐6 weeks. Co‐treatment with CcnE1‐siRNA once a week was sufficient to continuously block CcnE1 expression and cell‐cycle activity of hepatocytes and nonparenchymal cells, resulting in significantly ameliorated liver fibrosis and inflammation. Importantly, CcnE1‐siRNA also prevented progression of liver fibrosis if applied after onset of chronic liver injury. Conclusion: Therapeutic targeting of CcnE1 in vivo using RNAi is feasible and has high antifibrotic activity. (Hepatology 2017;66:1242‐1257).
A matter of life and death: substance‐caused and substance‐related fatalities in Ibiza in 2015
Authors: Santacroce Rita , Ruiz Bennasar Claudia , Sancho Jaraiz Juan Ramon , Fiori Federica , Sarchione Fabiola , Angelini Federica , Catalano Gabriella , Carenti Maria Luisa , Corkery John Martin , Schifano Fabrizio , Di Giannantonio Massimo , Martinotti Giovanni
Published: May 2017

Objectives and methods

In the framework of the EU‐funded project “EU‐Madness,” we collected and analysed all the reports of fatalities directly or indirectly related to substances of abuse registered in Ibiza from January to September 2015, in order to analyse the characteristics of the sample, the identified substances, and the nature of deaths associated with their consumption.

Results

A significant increase of substance‐caused deaths with respect to the previous 4 years has been highlighted. Most of the subjects were young males, more than half were not Spanish. Males prevailed also amongst the victims of traffic accidents and suicides. The most commonly involved substances included MDMA, alcohol, cocaine, THC, opiates and prescription drugs.

Conclusions

Although the use of NPS is rapidly increasing in Europe, according to the results from our sample, alcohol and well‐known stimulants (MDMA and cocaine) are still the substances of abuse mainly involved in the cases of substance‐caused and substance‐related fatalities. The significant increase of fatalities in Ibiza in the last 5 years is an issue that must be taken into account and should be better investigated, as other theories besides NPS‐increased diffusion should be proposed, and therefore, targeted prevention strategies should be designed.
Two‐photon imaging of fiber‐coupled neurons
Authors: Pochechuev M.S. , Fedotov I.V. , Ivashkina O.I. , Roshchina M.A. , Anokhin K.V. , Zheltikov A.M.
Published: May 2017

Optical coupling between a single, individually addressable neuron and a properly designed optical fiber is demonstrated. Two‐photon imaging is shown to enable a quantitative in situ analysis of such fiber–single‐neuron coupling in the live brain of transgenic mice. Fiber‐optic interrogation of single pyramidal neurons in mouse brain cortex is performed with the positioning of the fiber probe relative to the neuron accurately mapped by means of two‐photon imaging. These results pave the way for fiber‐optic interfaces to single neurons for a stimulation and interrogation of individually addressable brain cells in chronic in vivo studies on freely behaving transgenic animal models, as well as the integration of fiber‐optic single‐neuron stimulation into the optical imaging framework.

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FSOCA‐induced switchable footpad skin optical clearing window for blood flow and cell imaging in vivo
Authors: Shi Rui , Feng Wei , Zhang Chao , Zhang Zhihong , Zhu Dan
Published: May 2017

The mouse footpad for its feature of hairlessness provides an available window for imaging vascular and cellular structure and function in vivo. Unfortunately, the strong scattering of its skin limits the penetration of light and reduces the imaging contrast and depth. Herein, an innovative footpad skin optical clearing agent (FSOCA) was developed to make the footpad skin transparent quickly by topical application. The results demonstrate that FSOCA treatment not only allowed the cutaneous blood vessels and blood flow distribution to be monitored by laser speckle contrast imaging technique with higher contrast, but also permitted the fluorescent cells to be imaged by laser scanning confocal microscopy with higher fluorescence signal intensity and larger imaging depth. In addition, the physiological saline‐treatment could make the footpad skin recover to the initial turbid status, and reclearing would not induce any adverse effects on the distributions and morphologies of blood vessels and cells, which demonstrated a safe and switchable window for biomedical imaging. This switchable footpad skin optical clearing window will be significant for studying blood flow dynamics and cellular immune function in vivo in some vascular and immunological diseases. Picture: Repeated cell imaging in vivo before (a) and after (b) FSOCA treatment. (c) Merged images of 4 h (cyan border) or 72 h (magenta border) over 0 h. (d) Zoom of ROI in 4 h (yellow rectangle) or 72 h (red rectangle).
mTORC1 Inhibits NF-κB/NFATc1 Signaling and Prevents Osteoclast Precursor Differentiation, In Vitro and In Mice
Authors: Zhang Yue , Xu Song , Li Kai , Tan Kang , Liang Kangyan , Wang Jian , Shen Junhui , Zou Wenchong , Hu Le , Cai Daozhang , Ding Changhai , Li Mangmang , Xiao Guozhi , Liu Bin , Liu Anling , Bai Xiaochun
Published: May 2017

The mechanistic target of rapamycin complex 1 (mTORC1) is a critical sensor for bone homeostasis and bone formation; however, the role of mTORC1 in osteoclast development and the underlying mechanisms have not yet been fully established. Here, we found that mTORC1 activity declined during osteoclast precursors differentiation in vitro and in vivo. We further targeted deletion of Raptor (mTORC1 key component) or Tsc1 (mTORC1 negative regulator) to constitutively inhibit or activate mTORC1 in osteoclast precursors (monocytes/macrophages), using LyzM-cre mice. Osteoclastic formation was drastically increased in cultures of Raptor deficient bone marrow monocytes/macrophages (BMMs), and Raptor-deficient mice displayed osteopenia with enhanced osteoclastogenesis. Conversely, BMMs lacking Tsc1 exhibited a severe defect in osteoclast-like differentiation and absorptive function, both of which were restored following rapamycin treatment. Importantly, expression of nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) and nuclear factor of activated T cells, cytoplasmic 1 (NFATc1), transcription factors that are essential for osteoclast differentiation was negatively regulated by mTORC1 in osteoclast lineages. These results provide evidence that mTORC1 plays as a critical role as an osteoclastic differentiation-limiting signal and suggest a potential drawback in treating bone loss–related diseases with mTOR inhibitors clinically. © 2017 American Society for Bone and Mineral Research.
Proposal of size‐based surgical indication criteria for liver hemangioma based on a nationwide survey in Japan
Authors: Sakamoto Yoshihiro , Kokudo Norihiro , Watadani Takeyuki , Shibahara Junji , Yamamoto Masakazu , Yamaue Hiroki ,   the Japanese Society of Hepato‐Biliary‐Pancreatic Surgery
Published: May 2017

Background

Surgical indications for liver hemangioma remain unclear.

Methods

Of 510 patients undergoing surgical resection for liver hemangioma in 118 Japanese centers between 1998 and 2012, abdominal symptoms, diagnostic accuracy, and surgical outcomes were analyzed to propose size‐based surgical indications. Patients were classified into four groups based on tumor size: Group A ≤5 cm (n = 122, 24%), Group B 5–10 cm (n = 164, 32%), Group C 10–15 cm (n = 124, 24%), and Group D >15 cm (n = 100, 20%).

Results

Hemangiomas in Group A were most frequently diagnosed as malignant tumors (43.5%) due to the absence of typical imaging findings and with highest incidence of positive HBV (15.7%). Diagnostic accuracy was 98.4% in Groups B to D. Liver failure after hepatectomy was higher in Group D than in Groups A to C (3.0% vs. 0.5%, P = 0.02). Only one operative death was observed (0.2%) in Group D.

Conclusions

In patients with ≤5 cm hemangioma, surgical resection can be indicated when a malignant tumor cannot be ruled out. However, surgery for 5–10 cm asymptomatic hemangiomas should be limited. Experienced hepatic surgeons should conduct hepatectomy for tumors >15 cm to avoid serious morbidity or mortality.
Activated FGFR3 prevents subchondral bone sclerosis during the development of osteoarthritis in transgenic mice with achondroplasia
Authors: Okura Toshiaki , Matsushita Masaki , Mishima Kenichi , Esaki Ryusaku , Seki Taisuke , Ishiguro Naoki , Kitoh Hiroshi
Published: May 2017

The purpose of this study is to investigate the morphometric changes of the subchondral bone during the development of osteoarthritis (OA) in transgenic mice with achondroplasia (Fgfr3ach) carrying a heterozygous gain‐of‐function mutation in Fgfr3. Two OA models (spontaneously developed with age: The aging model, and surgically induced by destabilization of the medial meniscus: The DMM model) were established. Articular cartilage, epiphysis, and metaphysis of the knee joint were histologically and morphometrically compared between wild‐type mice, and Fgfr3ach mice in both OA models. Articular cartilage degeneration was scored according to the Osteoarthritis Research Society International (OARSI) scoring system. Several morphometric parameters including bone mineral density (BMD), bone volume/tissue volume (BV/TV), trabecular bone thickness (Tb.Th), and subchondral bone thickness in the medial tibial plateau (MTP) (Sb.Th med) were quantified by micro‐computed tomography (CT). In the aging model, although there were no significant differences in the OARSI score between wild‐type mice and Fgfr3ach mice, Sb.Th med and Tb.Th in the epiphysis significantly increased in wild‐type mice. In the DMM model, the OARSI score of the medial compartment was significantly lower in Fgfr3ach mice than in wild‐type mice. BMD, BV/TV, and Tb.Th in the epiphysis increased in wild‐type mice and unchanged in Fgfr3ach mice, and the Sb.Th med was significantly larger in wild‐type mice after surgery. Subchondral sclerosis, which preceded the cartilage degeneration, was inhibited in Fgfr3ach mice. Activated FGFR3 signaling prevented sclerotic changes of the subchondral bone and subsequent cartilage degeneration. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:300–308, 2018.
KMT2B rare missense variants in generalized dystonia
Authors: Zech Michael , Jech Robert , Havránková Petra , Fečíková Anna , Berutti Riccardo , Urgošík Dušan , Kemlink David , Strom Tim M. , Roth Jan , Růžička Evžen , Winkelmann Juliane
Published: May 2017

Background: Recently a novel syndrome of childhood‐onset generalized dystonia originating from mutations in lysine‐specific methyltransferase 2B (KMT2B) has been reported.

Methods: We sequenced the exomes of 4 generalized dystonia‐affected probands recruited from a Prague movement disorders center (Czech Republic). Bioinformatics analyses were conducted to select candidate causal variants in described dystonia‐mutated genes. After cosegregation testing, checklists from the American College of Medical Genetics and Genomics were adopted to judge variant pathogenicity.

Results: Three novel, predicted protein‐damaging missense variants in KMT2B were identified (p.Glu1234Lys, p.Ala1541Val, p.Arg1779Gln). Meeting pathogenicity criteria, p.Glu1234Lys was absent from population‐based controls, situated in a key protein domain, and had occurred de novo. The associated phenotype comprised adolescence‐onset generalized isolated dystonia with prominent speech impairment. Although linked to a similar clinical expression, p.Ala1541Val and p.Arg1779Gln remained of uncertain significance.

Conclusions: Rare missense variation in KMT2B represents an additional cause of generalized dystonia. Application of sequence interpretation standards is required before assigning pathogenicity to a KMT2B missense variant. © 2017 International Parkinson and Movement Disorder Society
Phase I study of perifosine monotherapy in patients with recurrent or refractory neuroblastoma
Authors: Matsumoto Kimikazu , Shichino Hiroyuki , Kawamoto Hiroshi , Kosaka Yoshiyuki , Chin Motoaki , Kato Koji , Mugishima Hideo
Published: May 2017

Purpose

Perifosine is an alkylphospholipid analog that inhibits or modulates signaling through signal transduction pathways such as Akt, which is enhanced in neuroblastoma (NB) by activation of tyrosine kinase receptors. We conducted a phase I study of perifosine in Japanese patients with recurrent or refractory NB.

Experimental Design

All patients enrolled were over 2 years of age; all had refractory or relapsed NB and a performance status of greater than 50%. Perifosine was orally administered at a loading dose (100–300 mg) on day 1 and at a maintenance dose (50–150 mg) from day 2 onward. Dose‐limiting toxicity (DLT) and pharmacokinetics were assessed in Step 1 and safety and efficacy in Step 2.

Results

Nineteen patients were recruited. No DLT was observed. Adverse reactions occurring in more than 30% of the patients were vomiting (63%), nausea (53%), and diarrhea (37%). The mean plasma concentration of perifosine was 27.5 ± 9.8 M on day 15 and 27.3 ± 11.5 M on day 29. The response rate (RR) in 18 patients evaluable according to modified International Neuroblastoma Response Criteria was 0%; the disease control rate (DCR) was 56%. Median progression‐free survival (PFS) was 122 days. In 11 patients evaluable according to the Response Evaluation Criteria in Solid Tumors, the RR and DCR were 9% and 55%, respectively. The median PFS was not reached.

Conclusions

Perifosine monotherapy was well tolerated in Japanese patients with recurrent/refractory NB. Further investigations in combination with other anticancer or molecular targeted agents are warranted.
Clinical case series of pediatric hepatic angiosarcoma
Authors: Grassia Kalee L. , Peterman Caitlin M. , Iacobas Ionela , Margolin Judith F. , Bien Ewa , Padhye Bhavna , Meyers Rebecka L. , Adams Denise M.
Published: May 2017

Hepatic angiosarcoma is a rare, aggressive, malignant neoplasm with fewer than 50 cases reported in children. Prognosis is poor, with a minority surviving beyond 2 years after diagnosis. We report eight cases of pediatric hepatic angiosarcoma, diagnosed at a mean age of 3 years. Seven were initially diagnosed with an infantile hepatic hemangioendothelioma (IHHE) or hemangioma and the eighth with a “vascular tumor.” Two patients, who received liver transplant, survived. We suggest hepatic hemangiomas can rarely transform into angiosarcomas and a subset of IHHEs (Type II) are actually a low‐grade form of angiosarcoma rather than a benign lesion.
Association of outcomes and anti‐Xa levels in the treatment of pediatric venous thromboembolism
Authors: Fan Jennifer L. , Roberts Laura E. , Scheurer Michael E. , Yee Donald L. , Shah Mona D. , Lee‐Kim YoungNa J.
Published: May 2017

Background

There are few data in the pediatric population evaluating the relationship between measured anti‐Xa levels during enoxaparin therapy and thrombotic outcomes.

Objective

To determine whether there is a difference in outcomes in children who receive enoxaparin with mean anti‐Xa levels between 0.45 and 0.79 unit/ml (low therapeutic range) versus between 0.80 and 1.05 unit/ml (high therapeutic range) throughout their course of their treatment.

Methods

We retrospectively identified subjects with uncomplicated venous thromboembolism treated with enoxaparin.

Results

Of 69 patients with any response to therapy, 48 (70%) had mean anti‐Xa levels in the low therapeutic range and 21 (30%) had mean anti‐Xa levels in the high therapeutic range. Of 20 patients with no documented response to therapy, 13 (65%) had mean anti‐Xa levels in the low therapeutic range and 7 (35%) had mean anti‐Xa levels in the high therapeutic range. Forty‐eight (79%) of the 61 patients with low‐range mean anti‐Xa level had any response to therapy. Twenty‐one (75%) of the 28 patients with high‐range mean anti‐Xa level had any response to therapy. Chi‐square test (P = 0.080) and logistic regression (OR = 1.23, P = 0.70) demonstrated no significant association between mean anti‐Xa range (lower vs. upper) and therapy response.

Conclusions

There was no statistically significant difference between low‐range versus high‐range mean anti‐Xa levels and thrombus resolution. Empiric clinical practices of targeting anti‐Xa levels in the higher therapeutic range to achieve better outcomes may not be warranted.
Association between CYP4F2 genotype and circulating plasma vitamin K concentration in children on chronic warfarin therapy: Possible long‐term implications for bone development and vascular health
Authors: Kampouraki Emmanouela , Avery Peter J. , Biss Tina , Kamali Farhad
Published: May 2017

Vitamin K is essential, for the activation of clotting proteins, as well as the biosynthesis of osteocalcin in bones and the activation of matrix‐Gla protein needed in maintaining vasculature health. Cytochrome p450 4F2 (CYP4F2) enzyme is involved in vitamin K catabolism. Genetic polymorphism in CYP4F2 is thus likely to affect vitamin K systemic availability. We show that children on chronic warfarin therapy have low levels of vitamin K and vitamin K levels are linked to CYP4F2 genotype. Long‐term low levels of vitamin K, influenced by CYP4F2 genotype, might affect bone development and vascular health in children on chronic warfarin therapy.
Experimental evaluation and modeling of thermal conductivity of tetrafunctional epoxy resin containing different carbon nanostructures
Authors: Romano Vittorio , Naddeo Carlo , Vertuccio Luigi , Lafdi Khalid , Guadagno Liberata
Published: May 2017

This study attempts to investigate the thermal conductivity behavior of epoxy nanocomposites containing different types of nanofillers, such as 1‐D Multiwall Carbon Nanotubes (MWCNTs) and 2‐D predominant shape of Exfoliated Graphite nanoparticles (EG) at loading level from 0.25 to 3% wt. For all the analyzed epoxy nanocomposites calorimetric investigation shows that EG nanoparticles accelerate the curing process of the epoxy resin. Thermal conductivity measurements show that this acceleration is directly related to the better heat conduction obtained through the incorporation of EG in the epoxy matrix. The thermal conductivity of epoxy nanocomposites filled with EG, unlike of epoxy nanocomposites containing MWCNTs, increases significantly with increasing content of nanofiller. An increase in thermal conductivity of ∼ 300% has been detected for a filler percentage of only 3%wt of EG.

The application of Deng‐Zheng micromechanical model has proven to be very effective in predicting analytically the thermal conductivity of the analyzed nanocomposites. POLYM. ENG. SCI., 57:779–786, 2017. © 2017 Society of Plastics Engineers
A new paradigm for accident investigation and analysis in the era of big data
Authors: Huang Lang , Wu Chao , Wang Bing , Ouyang Qiumei
Published: May 2017

The advent of the era of Big Data has spawned a new research paradigm and has transformed the outlook of numerous fields in science and engineering. Similarly, as one of the important fields of safety science, the area of accident investigation also has great opportunities for leveraging Big Data to its advantage. With this in mind, in this article, the influencing factors of accident investigation were analyzed. Then, the definition of Safety‐related Big Data (SRBD) was analyzed, and a four‐layer pyramidal structure consisting of SRBD, Safety Information, Safety Law, and Safety Knowledge was constructed. Based on this, the conceptual model of the accident investigation paradigm based on SRBD was proposed. Moreover, the opportunities offered by the proposed new paradigm were argued from three aspects, which are “tools,” “inputs,” and “constraints.” Last, the proposed paradigm was applied in a case study. Results show that the proposed paradigm can provide a novel method for accident investigation and analysis. The presented paper aims to explore the great expectations for accident investigation in the era of Big Data. © 2017 American Institute of Chemical Engineers Process Process Saf Prog 37:42–48, 2018
Abnormal polar nanoregion evolution in (Bi0.09Ba0.91)(Zn0.045Ti0.955)O3 (9BZT‐BT) ceramic
Authors: Shi Jing , Cui Naiyuan , Wang Xiaoli , Yun Sining
Published: May 2017

In this work, 9BZT‐BT ceramic has been studied by both experiment and theoretical ab initio molecular dynamics. In experiment, there are two sets of polar regions with different decay temperatures coexisting in the sample. With increasing temperature, one set gradually decomposes between −45 and −15 °C, whereas the other set keeps stable until much higher temperatures. Ab initio molecular dynamics simulations show that Bi3+−Zn2+ displacement coupling plays a crucial role at high temperatures to stabilize the micro‐domains and ergodic state polar nanoregions (PNRs). This mechanism could be used to explain the complex polarization behaviors and strong relaxor phenomenon observed in experiment.
Control of spin‐reorientation transition in (0001) oriented α‐Fe2O3 thin film by external magnetic field and temperature
Authors: Pati Satya Prakash , Al‐Mahdawi Muftah , Ye Shujun , Nozaki Tomohiro , Sahashi Masashi
Published: May 2017

A pure‐phase, unstrained and epitaxial α‐Fe2O3 film of thickness 250 nm has been fabricated by reactive rf sputtering over c‐Al2O3 substrate with nominal average surface roughness of 0.71 nm. Field induced spin‐reorientation temperature (TSR) and temperature dependent spin‐reorientation field (HSR) have been investigated. A linear relationship in the result has been found with ∂TSR/∂HSR equal to −0.92 ± 0.05 K kOe−1 and −0.89 ± 0.175 K kOe−1 by both methods, respectively. The field induced entropy change is argued to be the possible cause for the shift in the spin‐reorientation temperature with applied field. The entropy change associated with the first‐order phase transition is calculated on the basis of Clausius–Clapeyron equation and found to be 0.029 J kg−1 K−1.
Siblings of Children with Autism: the Siblings Embedded Systems Framework
Authors: Kovshoff Hanna , Cebula Katie , Tsai Hsiao-Wei Joy , Hastings Richard P.
Published: May 2017

Purpose of Review

A range of interacting factors/mechanisms at the individual, family, and wider systems levels influences siblings living in families where one sibling has autism. We introduce the Sibling Embedded Systems Framework which aims to contextualise siblings’ experience and characterise the multiple and interacting factors influencing family and, in particular, sibling outcomes.

Recent Findings

Findings from studies that have reported outcomes for siblings of children with autism are equivocal, ranging from negative impact, no difference, to positive experience. This is likely due to the complex nature of understanding the sibling experience. We focus on particular elements of the framework and review recent novel literature to help guide future directions for research and practice including the influence of culture, methodological considerations, and wider participatory methods.

The Siblings Embedded System Framework can be used to understand interactive factors that affect sibling adjustment and to develop clinically, educationally and empirically based work that aims to enhance and support sibling adjustment, relationships, and well-being in families of children with autism.
Consensus guidelines for lumbar puncture in patients with neurological diseases
Authors: Engelborghs Sebastiaan , Niemantsverdriet Ellis , Struyfs Hanne , Blennow Kaj , Brouns Raf , Comabella Manuel , Dujmovic Irena , van der Flier Wiesje , Frölich Lutz , Galimberti Daniela , Gnanapavan Sharmilee , Hemmer Bernhard , Hoff Erik , Hort Jakub , Iacobaeus Ellen , Ingelsson Martin , Jan de Jong Frank , Jonsson Michael , Khalil Michael , Kuhle Jens , Lleó Alberto , de Mendonça Alexandre , Molinuevo José Luis , Nagels Guy , Paquet Claire , Parnetti Lucilla , Roks Gerwin , Rosa‐Neto Pedro , Scheltens Philip , Skårsgard Constance , Stomrud Erik , Tumani Hayrettin , Visser Pieter Jelle , Wallin Anders , Winblad Bengt , Zetterberg Henrik , Duits Flora , Teunissen Charlotte E.
Published: May 2017

Introduction

Cerebrospinal fluid collection by lumbar puncture (LP) is performed in the diagnostic workup of several neurological brain diseases. Reluctance to perform the procedure is among others due to a lack of standards and guidelines to minimize the risk of complications, such as post‐LP headache or back pain.

Methods

We provide consensus guidelines for the LP procedure to minimize the risk of complications. The recommendations are based on (1) data from a large multicenter LP feasibility study (evidence level II‐2), (2) systematic literature review on LP needle characteristics and post‐LP complications (evidence level II‐2), (3) discussion of best practice within the Joint Programme Neurodegenerative Disease Research Biomarkers for Alzheimer's disease and Parkinson's Disease and Biomarkers for Multiple Sclerosis consortia (evidence level III).

Results

Our consensus guidelines address contraindications, as well as patient‐related and procedure‐related risk factors that can influence the development of post‐LP complications.

Discussion

When an LP is performed correctly, the procedure is well tolerated and accepted with a low complication rate.
Use of endoanal ultrasound as complimentary evaluation for detection of anal sphincter injury after vaginal birth
Authors: Izadpanah Ahmad , Izadpanah Ensieh , Lotfi Mehrzad , Samsami Alamtaj , Safarpour Alireza , Rezazadehkermani Mohammad
Published: May 2017

Purpose Anal sphincter injury after delivery is the main factor in the pathogenesis of fecal incontinence. Clinical obvious and specific injury to anal canal sphincter is seen in 3% of vaginal deliveries. There are many women who do not have a clear and specific laceration but they are damaged by sphincter muscles of anal canal. The purpose of the present study is to investigate the frequency of occult anal sphincter injury after vaginal delivery by Endo-anal sonography.

Methods Fifty women with first pregnancy were assessed at 27–33 weeks of pregnancy, and at 6 weeks and 6 months after vaginal delivery by questionnaire, examination and Endo-anal sonography. Women age, duration of delivery, the effect of epidural anesthesia, episiotomy and birth weight were studied and Endo-anal sonography results were recorded. Anal manometry was performed for all mothers before delivery and 5 ones with sphincter injury at 6 months and 3 years after delivery.

Results Five (10%) patients, with mean age 29.4 ± 6.5 years, mean neonatal weight of 3874 ± 287, and mean duration of delivery 11.6 ± 1.51 h, had signs of sphincter injury in Endo-anal sonography. The injury was persisted at six months after delivery. Also, significant differences were seen between anal manometry before delivery and 6 months and 3 years after delivery (p = 0.006 for mean squeezing pressure) in the five mothers.

Conclusion Endo-anal sonography might be a good screening tool for early detection of postpartum anal sphincter damages. However, further prospective cost benefit studies should be performed to propose it as a standard of care.
It Takes Two to Tango: Engaging Patients and Providers With Portals
Authors: Shah Sachin D. , Liebovitz David
Published: May 2017

Patient portals are designed to be tools to more fully engage patients in their health care and help enable them to better manage their own health information. As the U.S. health care system rapidly adopted electronic health records (EHRs) over the past decade, many with linked patient portals, enthusiasm and expectations for this new technology as a means to engage and empower patients grew. Most patient portals have a set of core features designed to facilitate health care transactions, information tracking, and communication with care team members. The evidence supporting the anticipated benefits of patient portals on patient outcomes, however, remains mixed and incomplete. Moreover, a paradox exists in that, despite a high consumer interest in patient portals, widespread adoption remains relatively low. Potential reasons include the need for greater provider endorsement, examination and adaptation of clinical workflows, and the recognition of patient engagement as a reciprocal process.
Technology‐Enabled Population Health Management: Two Communities' Use of an Electronic Care Alert System
Authors: Rowland Todd , Nielsen‐Farrell Jill , Church Kathy , Riddell Barbara
Published: May 2017

Population health management is an approach to improve the health outcomes of a specific group of people, such as frequent users of the emergency department or those at high‐risk for hospital admissions. When combined with quality improvement strategies, the targeted application of health information exchange and health information technology (health IT) can swiftly move health care systems and providers from basic to advanced population health management. One such tool is an electronic alert system (alert system), which informs a provider or site about a patient's visit to the emergency department or hospital admission on a daily basis. This article highlights the use of such an alert system in 2 communities to help address gaps in population health management.
Crisis and Recovery: The Cost of Sustainable Development in Nuragic Sardinia
Authors: Ialongo Nicola
Published: May 2017

Crises are thresholds in human history, often marking substantial transformations in societies. Crises, however, are not instants in time. They start, unfold, and develop in a process that is often traumatic for social systems, with outcomes ranging from catastrophe to complete recovery. In this article, catastrophic models are employed to understand a non-catastrophic outcome: the complete recovery that nuragic Sardinia experienced after a long crisis, caused in the first place by unsustainable strategies of territorial expansion. Starting from the premises of the ‘Tragedy of the Commons’, it is argued that the transformation of nuragic society was the best way of avoiding the constraints that the social structure imposed on the perspective of a sustainable growth. The study is based on a geostatistical analysis of a large sample of settlements, and it attempts to quantify population growth ratios for the Late Bronze Age.
Mild mixing of certain interval-exchange transformations
Authors: ROBERTSON DONALD
Published: May 2017

We prove that irreducible, linearly recurrent, type W interval-exchange transformations are always mild mixing. For every irreducible permutation, the set of linearly recurrent interval-exchange transformations has full Hausdorff dimension.