bluuebunny/crossref_metadata_2025 huggingface dataset:
Iron chelation therapy
Authors: HOFFBRAND A.V. , WONKE B.
Published: September 2018

Desferrioxamine (DFX) remains the most effective and safe iron chelator for treatment of patients with transfusional iron overload. It is usually given by intermittent subcutaneous infusions for 8–12 h on 4–6 days weekly using a battery‐driven pump. Disposable balloon infusers provide a suitable method of giving continuous subcutaneous infusions with improved patient compliance. For patients with cardiac abnormalities due to iron overload, continuous intravenous desferrioxamine is essential to eliminate toxic plasma non‐transferrin bound iron and to reduce body iron stores.

Deferiprone (L1, 1–2 dimethy1‐3hydroxy‐pyrid‐4‐one) is a less effective iron chelator but has the advantage of being orally active. Long‐term trials in which patients have taken 75 mg/kg/day have shown that deferiprone is capable of maintaining body iron stores at safe levels in a proportion of thalassaemia major patients but body iron stores, assessed by liver biopsy remain at high levels (>15.0 mg/g dry weight) in a substantial number of patients. These concentrations have been associated with tissue damage. Trials of increased doses of deferiprone (up to 100 mg/kg/day) or of combined therapy with daily deferiprone and DFX or 1 or 2 days each week are being carried out in an attempt to achieve lower body iron burden in these patients. Preliminary results show that the drugs can be given safely together and urine iron excretion produced is additive, implying that the drugs chelate different body iron pools.

Patients previously well chelated with serum ferritin levels less than 2500 μg/L have the fewest side‐effects from deferiprone and usually may be kept at the same level of body iron for periods of at least 4 years, assessed by serum ferritin and urine iron excretion. The side‐effects of deferiprone result in some patients discontinuing therapy. These side‐effects, especially arthropathy, mainly occur in previously poorly chelated and so the most heavily iron‐loaded patients. Nausea and other gastrointestinal symptoms, agranulocytosis or milder degrees of neutropenia account with arthropathy for nearly all the withdrawals from deferiprone therapy. Patients with cardiomyopathy due to iron overload should be given intravenous DFX rather than deferiprone. Deferiprone, licensed for pharmaceutical use in India, awaits official approval for widespread clinical use in Western Europe and North America. Meanwhile, attempts to find new orally active iron chelators and improved methods of administration of desferrioxamine are in progress.
Bone marrow transplantation for thalassaemia
Authors: LUCARELLI G.
Published: September 2018

For all patients with a histocompatibiliy antigen (HLA) identical donor we are actually using two protocols to whom the patient is assigned. This is based on which class the patients belongs to at the time of bone‐marrow transplant and is independent from the patient's age. For 116 patients in Class 1 and for 271 patients in Class 2 prepared for the transplant with bulsulfan 14 mg/kg, cyclophosphamide 200 mg/kg and cyclosporin alone, the probabilities of survival and of event‐free survival are 95% and 90% for Class 1 and 85% and 81% for Class 2. For 125 Class 3 patients prepared for the transplant with busulfan 14 mg/kg, cyclophosphamide reduced to 120–160 mg/kg, cyclosporin and ‘short’ methotrexate, the probabilities of survival and of event‐free survival are 78% and 54%. For 108 adult patients aged between 17 and 35 years, who underwent the transplant after preparation with the same protocol used for the Class 2 or Class 3 patients, the probabilities of survival are 67% and of event‐free survival are 63%. Bone marrow transplantation remains the only form of radical treatment of thalassaemia in those patients with an HLA identical donor.
Apparent inbreeding preference despite inbreeding depression in the American crow
Authors: Townsend Andrea K. , Taff Conor C. , Jones Melissa L. , Getman Katherine H. , Wheeler Sarah S. , Hinton Mitch G. , Logsdon Ryane M.
Published: September 2018

Although matings between relatives can have negative effects on offspring fitness, apparent inbreeding preference has been reported in a growing number of systems, including those with documented inbreeding depression. Here, we examined evidence for inbreeding depression and inbreeding preference in two populations (Clinton, New York, and Davis, California, USA) of the cooperatively breeding American crow (Corvus brachyrhynchos). We then compared observed inbreeding strategies with theoretical expectations for optimal, adaptive levels of inbreeding, given the inclusive fitness benefits and population‐specific magnitude of inbreeding depression. We found that low heterozygosity at a panel of 33 microsatellite markers was associated with low survival probability (fledging success) and low white blood cell counts among offspring in both populations. Despite these costs, our data were more consistent with inbreeding preference than avoidance: The observed heterozygosity among 396 sampled crow offspring was significantly lower than expected if local adults were mating by random chance. This pattern was consistent across a range of spatial scales in both populations. Adaptive levels of inbreeding, given the magnitude of inbreeding depression, were predicted to be very low in the California population, whereas complete disassortative mating was predicted in the New York population. Sexual conflict might have contributed to the apparent absence of inbreeding avoidance in crows. These data add to an increasing number of examples of an “inbreeding paradox,” where inbreeding appears to be preferred despite inbreeding depression.
Solving large‐data consistency problems at Statistics Netherlands using macro‐integration techniques
Authors: Mushkudiani Nino , Daalmans Jacco , Bikker Reinier
Published: September 2018

The generalized multivariate Denton model for achieving consistency between large accounting frameworks developed at Statistics Netherlands (SN) is originally intended for benchmarking of supply and use (SU) tables of national accounts. The success of this application in the production process triggered using the model for other processes within the office. Currently, at SN, many production processes of national accounts, but also other departments, use the modifications of this optimization model for achieving consistency of data obtained from different sources. These include reconciliation and benchmarking of SU tables and of institutional sector accounts, ESA (European system of accounts), revisions of SU tables, benchmarking of gross fixed capital formation, Population Census tables, and energy statistics figures. The mathematical model is based on a quadratic optimization function and combines different features, such as linear constraints, ratio constraints, weights, soft and hard constraints, and inequalities. The optimization problems we deal with can be very large, consisting of 500,000 variables and over 100,000 constraints. This optimization problem is solved using the commercially available software tool XPRESS and the free software tool R. For the reconciliation of trade and transport statistics, similar optimization techniques are used. In this paper, we give an overview of production processes at SN using macro‐integration techniques.
The role of stress in controlling infrared radiation during coal and rock failures
Authors: Ma Liqiang , Sun Hai , Zhang Yao , Hu Honglei , Zhang Chengguo
Published: September 2018

During coal failure under loading, variations in infrared radiation (IR) characteristics can be observed in response to stress drops. To explore the quantitative relation between the stress and IR characteristics, a new quantitative failure indicator called the variance of successive minus infrared image temperature (VSMIT) has been developed to study IR characteristics during the uniaxial compression loading. Results from this study indicate that the role of stress in controlling IR characteristics of the coal sample is universal during loading with the ratio of 90.2%. In addition, the role of stress in controlling IR is significant, given that the average sudden change coefficient of VSMIT is at least three orders of magnitudes of the stress drop coefficient of the coal sample. Moreover, the control effect has predictability (precursor). Before failure and instability, simultaneous sudden changes of VSMIT and stress can be observed in 76.2% of coal samples, which can thus be regarded as the IR precursor of coal failure. The present work can provide a new method and some novel indexes for monitoring stress state as well as fracture development in coal rocks, which will also be of theoretical guidance for promoting the applications of IR‐based forecasting and early warning of some natural and rock engineering disasters mainly including rockbursts and coalbursts induced by the fractures in the coal rock.
Successful heart‐kidney transplantation from a Hepatitis C viremic donor to negative recipient: One year of follow‐up
Authors: Wettersten Nicholas , Tran Hao , Mekeel Kristin , Pretorius Victor , Adler Eric , Aslam Saima
Published: September 2018

Every year the number of patients waiting for a heart transplant increases faster than the number of available donor organs. Some potential donor organs are from donors with active communicable diseases, including hepatitis C virus (HCV), potentially making donation prohibitive. The advent of direct‐acting antiviral agents for HCV has drastically changed the treatment of HCV. Recently, these agents have been used to treat HCV in organ donor recipients who acquired the disease from the donor organ. We report a case of heart‐kidney transplantation from an HCV viremic donor to HCV negative recipient with successful treatment and sustained virologic response.
Reviewing the Effect of 10 Days of Intense Exercise Period on Certain Blood Parameters of Tennis Players
Authors: Selcuk Muzaffer , Cinar Vedat , Sarikaya Mucahit , Oner Salih
Published: September 2018

This study aims to observe the possible negative effects that might occur on bio-chemistry and hemogram values of tennis players during the intense competition period by comparing the blood values of pre-competition period with 10 days of intense exercise. Blood samples were obtained from tennis team players who do not have any specific health problems and who study in university and regularly exercise. Mean age of the athletes are 22,40 ± 3,20 years and mean height is 179,83 ± 7,57 cm. This study is performed with 14 volunteer tennis players. Blood samples are obtained during the first day of the intense exercise program after the exercise, last day of the exercises and also right after the exercises. As per the obtained data, descriptive statistics are run (mean and standard deviation) and in order to compare the values of before and after the 10 days of intense exercise, Wilcoxon two related sample test was used. As per the results of the blood tests from before and after the exercise period, it is seen that values such as AST, ALT, MCH, MCHC and CK showed statistical significance (P<0.05). The athletes who prepared for the competitions with these values showed positive increases in bio-chemistry and hemogram values.
Hip and Trunk Muscle Activity During the Star Excursion Balance Test in Healthy Adults
Authors: Bhanot Kunal , Kaur Navpreet , Brody Lori Thein , Bridges Jennifer , Berry David C. , Ode Joshua J.
Published: September 2018

Context: Dynamic balance is a measure of core stability. Deficits in the dynamic balance have been related to injuries in the athletic populations. The Star Excursion Balance Test (SEBT) is suggested to measure and improve dynamic balance when used as a rehabilitative tool. Objective: To determine the electromyographic activity of the hip and the trunk muscles during the SEBT. Design: Descriptive. Setting: University campus. Participants: Twenty-two healthy adults (11 males and 11 females; 23.3 [3.8] y, 170.3 [7.6] cm, 67.8 [10.3] kg, and 15.1% [5.0%] body fat). Intervention: Surface electromyographic data were collected on 22 healthy adults of the erector spinae, external oblique, and rectus abdominis bilaterally, and gluteus medius and gluteus maximus muscle of the stance leg. A 2-way repeated measures analysis of variance was used to determine the interaction between the percentage maximal voluntary isometric contraction (%MVIC) and the reach directions. The %MVIC for each muscle was compared across the 8 reach directions using the Sidak post hoc test with α at .05. Main Outcome Measures: %MVIC. Results: Significant differences were observed for all the 8 muscles. Highest electromyographic activity was found for the tested muscles in the following reach directions—ipsilateral external oblique (44.5% [38.4%]): anterolateral; contralateral external oblique (52.3% [40.8%]): medial; ipsilateral rectus abdominis (8% [6.6%]): anterior; contralateral rectus abdominis (8% [5.3%]): anteromedial; ipsilateral erector spinae (46.4% [20.2%]): posterolateral; contralateral erector spinae (33.5% [11.3%]): posteromedial; gluteus maximus (27.4% [11.7%]): posterior; and gluteus medius (54.6% [26.1%]): medial direction. Conclusions: Trunk and hip muscle activation was direction dependent during the SEBT. This information can be used during rehabilitation of the hip and the trunk muscles.
Quantifying Functional Ankle Rehabilitation Progression Criteria Using GPS: A Preliminary Study
Authors: Greig Matt , Emmerson Hannah , McCreadie John
Published: September 2018

Context: Contemporary developments in Global Positioning System (GPS) technology present a means of quantifying mechanical loading in a clinical environment with high ecological validity. However, applications to date have typically focused on performance rather than rehabilitation. Objective: To examine the efficacy of GPS microtechnology in quantifying the progression of loading during functional rehabilitation from ankle sprain injury, given the prevalence of reinjury and need for quantifiable monitoring. Furthermore, to examine the influence of unit placement on the clinical interpretation of loading during specific functional rehabilitation drills. Design: Repeated measures. Setting: University athletic facilities. Participants: Twenty-two female intermittent team sports players. Intervention: All players completed a battery of 5 drills (anterior hop, inversion hop, eversion hop, diagonal hop, and diagonal hurdle hop) designed to reflect the mechanism of ankle sprain injury, and progress functional challenge and loading. Main Outcome Measures: GPS-mounted accelerometers quantified uniaxial PlayerLoad for each drill, with units placed at C7 and the tibia. Main effects for drill type and GPS location were investigated. Results: There was a significant main effect for drill type (P < .001) in the mediolateral (η2 = .436), anteroposterior (η2 = .480), and vertical planes (η2 = .516). The diagonal hurdle hop elicited significantly greater load than all other drills, highlighting a nonlinear progression of load. Only the mediolateral load showed evidence of progressive increase in loading. PlayerLoad was significantly greater at the tibia than at C7 for all drills, and in all planes (P < .001, η2 ≥ .662). Furthermore, the tibia placement was more sensitive to between-drill changes in mediolateral load than the C7 placement. Conclusions: The placement of the GPS unit is imperative to clinical interpretation, with both magnitude and sensitivity influenced by the unit location. GPS does provide efficacy in quantifying multiplanar loading during (p)rehabilitation, in a field or clinical setting, with potential in extending GPS analyses (beyond performance metrics) to functional injury rehabilitation and prevention.
Comparing the Effects of SUREE Programs on People With Scapular Downward Rotation Syndrome: A Randomized Clinical Trial
Authors: Derakhshani Alireza , Letafatkar Amir , Khosrokiani Zohre
Published: September 2018

Context:Scapular downward rotation syndrome (SDRS) is an impaired alignment that causes shoulder and neck pain. Interventions may lead to the reduction of pain intensity and joint position error (JPE) and improved range of motion (ROM).Objective:To evaluate the effects of 6-week Scapular Upward Rotation and Elevation Exercises (SUREE) with and without visual feedback on pain, ROM, and JPE in people with SDRS.Study Design:Randomized control trial.Setting:Institutional practice.Participants:Forty-two young and active subjects (22.61 [1.80] y; 27 males and 15 females) with unilateral SDRS randomly assigned into 3 groups (2 intervention groups and 1 control group).Interventions:SUREE without and with visual feedback programs.Main Outcome Measures:Pain, neck-flexion and rotation ROMs, and JPE were measured using visual analog scale (score), double inclinometer method, universal goniometer method (degrees), and a dual digital inclinometer (degrees), respectively, before and after interventions.Results:The results showed statistically significant changes within the experimental groups in all variables except for the neck rotation ROM in the SUREE intervention without visual feedback (P < .05). However, there were no changes in the control group before and after the interventions in all dependent variables (P < .05). Also, there were no significant differences between both experimental groups concerning all dependent variables except for the rotation ROM (P < .05).Conclusion:The results suggest that the 6-week SUREE with and without visual feedback programs result in decreased neck pain and improved flexion ROM and JPE during active neck motions in subjects with unilateral SDRS. However, the 6-week SUREE with visual feedback may improve the neck rotation ROM in subjects with unilateral SDRS. However, further studies are needed to confirm the results of this study.
Using the Selective Functional Movement Assessment for the Evaluation of Dancers’ Functional Limitations and Dysfunctions: A Critically Appraised Topic
Authors: Fauntroy Victoria , Fyock Marcie , Hansen-Honeycutt Jena , Nolton Esther , Ambegaonkar Jatin P.
Published: September 2018

Clinical Scenario: Dancers participate in a functionally demanding activity. Athletic participation typically requires the completion of a preparticipation examination, which involves a functional movement screen offering insight into potential injury recognition. The Selective Functional Movement Assessment (SFMA) was created to measure the status of movement–pattern-related pain and dysfunction using regionally interdependent movement to aggravate symptoms and exhibit limitations and dysfunctions. Still, a functional assessment has not been identified to recognize potential dysfunctions or limitations in this population. Clinical Question: Does the use of the SFMA improve overall evaluation of dancers by providing more information on a dancer’s overall functional ability and limitations? Summary of Key Findings: The literature search discovered 12 studies and 3 books in which 4 studies were included (2 case reviews, 1 case report, and 1 original research study) based on the inclusion and exclusion criteria. Three of the studies provided clinical case studies utilizing the SFMA to improve the patient’s dysfunctions, whereas 1 study examined the intrarater and interrater reliability of the SFMA. In 3 studies, participants displayed less movement dysfunction. The authors from 3 of the studies agreed the SFMA was a valuable tool for clinicians to use during evaluations, as it provided a more holistic view of the patient, discovering dysfunctional movement patterns that may better identify the source of injury. Clinical Bottom Line: Low-quality evidence, defined as poorly designed case studies, case series, and cohort studies, exist that supports improvement of overall evaluations when utilizing the SFMA. Although the studies were considered low-quality evidence, each included study displayed an effective use of the SFMA as an overall evaluation that correctly identified dysfunctional movement patterns. Strength of Recommendation: Grade C evidence exists that the SFMA contributes to the functional evaluation used in dancers.
Comparative Epidemiology of Vancomycin-Resistant Enterococci Colonization in an Acute-Care Hospital and Its Affiliated Intermediate- and Long-Term Care Facilities in Singapore
Authors: Tan Damon , Htun Htet Lin , Koh Jocelyn , Kanagasabai Kala , Lim Jia-Wei , Hon Pei-Yun , Ang Brenda , Chow Angela
Published: September 2018

Vancomycin-resistant enterococci (VRE) are an important cause of nosocomial infections in acute-care hospitals (ACHs), intermediate-care facilities (ITCFs), and long-term care facilities (LTCFs). This study contemporaneously compared the epidemiology and risk factors for VRE colonization in different care settings in a health care network.
Bioaerosol Sampler Choice Should Consider Efficiency and Ability of Samplers To Cover Microbial Diversity
Authors: Mbareche Hamza , Veillette Marc , Bilodeau Guillaume J. , Duchaine Caroline
Published: September 2018

Associating bioaerosol exposure and health problems is challenging, and adequate exposure monitoring is a priority for scientists in the field. Conclusions that can be drawn from bioaerosol exposure studies are highly dependent on the design of the study and the methodologies used. The air sampling strategy is the first methodological step leading to an accurate interpretation of what is present in the air. Applying new molecular approaches to evaluate the efficiencies of the different types of samplers used in the field is necessary in order to circumvent traditional approaches and the biases they introduce to such studies. The results and conclusions provided in this paper should be taken in consideration when conducting a bioaerosol study.
CRISPR-Cas9 and CRISPR-Assisted Cytidine Deaminase Enable Precise and Efficient Genome Editing in Klebsiella pneumoniae
Authors: Wang Yu , Wang Shanshan , Chen Weizhong , Song Liqiang , Zhang Yifei , Shen Zhen , Yu Fangyou , Li Min , Ji Quanjiang
Published: September 2018

Genetics is a key means to study bacterial physiology. However, the highly desirable scarless genetic manipulation is often time-consuming and laborious for the major human pathogen
K. pneumoniae
. We developed a CRISPR-Cas9-mediated genome-editing method and a cytidine base-editing system, enabling rapid, highly efficient, and iterative genome editing in both industrial and clinically isolated
K. pneumoniae
strains. We applied both tools in dissecting the drug resistance mechanism of a hypermucoviscous carbapenem-resistant
K. pneumoniae
strain, elucidating that the
bla
KPC-2
gene was the major factor that contributed to the carbapenem resistance of the hypermucoviscous carbapenem-resistant
K. pneumoniae
strain. Utilization of the two tools will dramatically accelerate a wide variety of investigations in diverse
K. pneumoniae
strains and relevant
Enterobacteriaceae
species, such as gene characterization, drug discovery, and metabolic engineering.
Floxed-Cassette Allelic Exchange Mutagenesis Enables Markerless Gene Deletion in Chlamydia trachomatis and Can Reverse Cassette-Induced Polar Effects
Authors: Keb G. , Hayman R. , Fields K. A.
Published: September 2018

C. trachomatisinfections represent a significant burden to human health. The ability to genetically manipulateChlamydiaspp. is overcoming historic confounding barriers that have impeded rapid progress in understanding overall chlamydial pathogenesis. The current state of genetic manipulation inChlamydiaspp. requires further development, including mechanisms to generate markerless gene disruption. We leveraged a stepwise Cre-lox approach to excise selection marker genes from a deleted gene locus. We found this process to be efficient, and the removal of extraneous elements resulted in the reversal of a negative polar effect on a downstream gene. This technique facilitates a more direct assessment of gene function and adds to theChlamydiamolecular toolbox by facilitating the deletion of genes within operons.
Evaluation of Risk Factors for Clostridium difficile Infection Based on Immunochromatography Testing and Toxigenic Culture Assay
Authors: Ohshima Toshio , Osaki Takako , Yamamoto Yukari , Asai Satomi , Miyachi Hayato , Kamiya Shigeru
Published: September 2018

In recent years, the diagnostic method of choice for
Clostridium difficile
infection (CDI) is a rapid enzyme immunoassay in which glutamate dehydrogenase (GDH) antigen and
C. difficile
toxin can be detected (
C. diff
Quik Chek Complete; Alere Inc.) (Quik Chek).
Host Enzymes Heparanase and Cathepsin L Promote Herpes Simplex Virus 2 Release from Cells
Authors: Hopkins James , Yadavalli Tejabhiram , Agelidis Alex M. , Shukla Deepak
Published: September 2018

Genital infections by HSV-2 represent one of the most common sexually transmitted viral infections. The virus causes painful lesions and sores around the genitals or rectum. Intermittent release of the virus from infected tissues during sexual activities is the most common cause of transmission. At the molecular level, cell surface heparan sulfate (HS) is known to provide attachment sites for HSV-2. While the removal of HS during HSV-1 release has been shown, not much is known about the host factors and their regulators that contribute to HSV-2 release from natural target cell types. Here we suggest a role for the host enzyme heparanase in HSV-2 release. Our work reveals that in addition to the regulation of transcription by NF-κB, HPSE is also regulated posttranslationally by cathepsin L and that inhibition of heparanase activity directly affects HSV-2 release. We provide unique insights into the host mechanisms controlling HSV-2 egress and spread.
Trends in mental health service utilisation in immigrant youth in Ontario, Canada, 1996–2012: a population-based longitudinal cohort study
Authors: Saunders Natasha Ruth , Lebenbaum Michael , Lu Hong , Stukel Therese A , Urquia Marcelo Luis , Guttmann Astrid
Published: September 2018

Objective

To describe trends in mental health service use of youth by immigration status and characteristics.

Design

Population-based longitudinal cohort study from 1996 to 2012 using linked health and administrative datasets.

Setting

Ontario, Canada.

Participants

Youth 10–24 years, living in Ontario, Canada.

Exposure

The main exposure was immigration status (recent immigrants vs long-term residents). Secondary exposures were region of origin and refugee status.

Main outcome measure

Mental health hospitalisations, emergency department (ED) visits and outpatient visits within consecutive 3-year time periods. Poisson regression models estimated rate ratios (RR).

Results

Over 2.5 million person years per period were included. Rates of recent immigrant mental health service utilisation were at least 40% lower than long-term residents (p<0.0001).

Mental health hospitalisation and ED visit rates increased in long-term residents (hospitalisations, RR 1.09 (95% CI 1.08 to 1.09); ED visits, RR 1.15 (1.14 to 1.15)) and recent immigrants (hospitalisations RR 1.05 (1.03 to 1.07); ED visits, RR 1.08 (1.05 to 1.11)). Mental health outpatient visit rates increased in long-term residents (RR 1.03 (1.03 to 1.03)) but declined in recent immigrant (RR 0.94 (0.93 to 0.95)). Comparable divergent trends in acute care and outpatient service use were observed among refugees and across most regions of origin. Recent immigrant acute care use was driven by longer-term refugees (hospitalisations RR 1.12 (1.03 to 1.21); ED visits RR 1.11 (1.02 to 1.20)).

Conclusions

Mental health service utilisation was lower among recent immigrants than long-term residents. While acute care use is increasing at a faster rate among long-term residents than recent immigrants, the decrease in outpatient mental health visits in immigrants highlights a potential emerging disparity in access to preventative care.
Cohort profile: Thrombolysis in Ischemic Stroke Patients (TRISP): a multicentre research collaboration
Authors: Scheitz Jan F , Gensicke Henrik , Zinkstok Sanne M , Curtze Sami , Arnold Marcel , Hametner Christian , Pezzini Alessandro , Turc Guillaume , Zini Andrea , Padjen Visnja , Wegener Susanne , Nordanstig Annika , Kellert Lars , Kägi Georg , Bejot Yannick , Michel Patrik , Leys Didier , Nolte Christian H , Nederkoorn Paul J , Engelter Stefan T
Published: September 2018

Purpose

The ThRombolysis in Ischemic Stroke Patients (TRISP) collaboration aims to address clinically relevant questions about safety and outcomes of intravenous thrombolysis (IVT) and endovascular thrombectomy. The findings can provide observational information on treatment of patients derived from everyday clinical practice.

Participants

TRISP is an open, investigator-driven collaborative research initiative of European stroke centres with expertise in treatment with revascularisation therapies and maintenance of hospital-based registries. All participating centres made a commitment to prospectively collect data on consecutive patients with stroke treated with IVT using standardised definitions of variables and outcomes, to assure accuracy and completeness of the data and to adapt their local databases to answer novel research questions.

Findings to date

Currently, TRISP comprises 18 centres and registers >10 000 IVT-treated patients. Prior TRISP projects provided evidence on the safety and functional outcome in relevant subgroups of patients who were excluded, under-represented or not specifically addressed in randomised controlled trials (ie, pre-existing disability, cervical artery dissections, stroke mimics, prior statin use), demonstrated deficits in organisation of acute stroke care (ie, IVT during non-working hours, effects of onset-to-door time on onset-to-needle time), evaluated the association between laboratory findings on outcome after IVT and served to develop risk estimation tools for prediction of haemorrhagic complications and functional outcome after IVT.

Future plans

Further TRISP projects to increase knowledge of the effect and safety of revascularisation therapies in acute stroke are ongoing. TRISP welcomes participation and project proposals of further centres fulfilling the outlined requirements. In the future, TRISP will be extended to include patients undergoing endovascular thrombectomy.
Future projection of the physician workforce and its geographical equity in Japan: a cohort-component model
Authors: Hara Koji , Kunisawa Susumu , Sasaki Noriko , Imanaka Yuichi
Published: September 2018

Introduction

The geographical inequity of physicians is a serious problem in Japan. However, there is little evidence of inequity in the future geographical distribution of physicians, even though the future physician supply at the national level has been estimated. In addition, possible changes in the age and sex distribution of future physicians are unclear. Thus, the purpose of this study is to project the future geographical distribution of physicians and their demographics.

Methods

We used a cohort-component model with the following assumptions: basic population, future mortality rate, future new registration rate, and future in-migration and out-migration rates. We examined changes in the number of physicians from 2005 to 2035 in secondary medical areas (SMAs) in Japan. To clarify the trends by regional characteristics, SMAs were divided into four groups based on urban or rural status and initial physician supply (lower/higher). The number of physicians was calculated separately by sex and age strata.

Results

From 2005 to 2035, the absolute number of physicians aged 25–64 will decline by 6.1% in rural areas with an initially lower physician supply, but it will increase by 37.0% in urban areas with an initially lower supply. The proportion of aged physicians will increase in all areas, especially in rural ones with an initially lower supply, where it will change from 14.4% to 31.3%. The inequity in the geographical distribution of physicians will expand despite an increase in the number of physicians in rural areas.

Conclusions

We found that the geographical disparity of physicians will worsen from 2005 to 2035. Furthermore, physicians aged 25–64 will be more concentrated in urban areas, and physicians will age more rapidly in rural places than urban ones. The regional disparity in the physician supply will worsen in the future if new and drastic measures are not taken.
Evaluating the effect of income support policies on social health inequalities (SHIs) at birth in Montreal and Brussels using a contextualised comparative approach and model family method: a study protocol
Authors: Sow Mouctar , De Spiegelaere Myriam , Raynault Marie-France
Published: September 2018

Introduction

Assessing the effects of social policies on social health inequalities (SHIs) is a complex issue. Variations in social policy between countries or regions provide natural experiments in policy implementation to perform comparative research. Comparisons are most enlightening when: the object of the evaluation is well defined (types of policies, population groups); the context of policy is analysed (history, implementation); the impact of policy on household poverty is outlined in detail; the influence of various factors (other than poverty) on SHI is taken into consideration.

Methods and analysis

This study aims to understand how income support policies (ISPs) in Brussels and Montreal influence the poverty level of households receiving social assistance, and how they are associated with SHI at birth. Two cases studies will be carried out from a comparative perspective. The analysis includes four stages : (1) The model family method will be used to compare ISPs and their impact on disposable income and poverty of households receiving social assistance in both regions. (2) Statistical analysis of administrative databases will enable the description and comparison of SHI in adverse pregnancy outcomes across the two regions. (3) Analysis of databases and documents will allow for description of various factors which are likely to interact with poverty and influence SHI at birth. (4) Based on the Diderichsen model, results from the previous stages will be used to formulate hypotheses about the mechanisms by which ISPs contribute to increasing or reducing SHI at birth in both regions.

Ethics and dissemination

This research was approved by the Human Research Ethics Committee for Health research of Université de Montréal. In Belgium, the access to linked databases was approved by the Commission for the Protection of Privacy. Databases de-identified according to Belgian and Canadian legislation will be used. Results will be disseminated in scientific publications and will be shared with policy makers and field actors through collaborations with local organisations in Brussels and Montreal.
Pain and the immune system: emerging concepts of IgG-mediated autoimmune pain and immunotherapies
Authors: Xu Min , Bennett David L H , Querol Luis Antonio , Wu Long-Jun , Irani Sarosh R , Watson James C , Pittock Sean J , Klein Christopher J
Published: September 2018

The immune system has long been recognised important in pain regulation through inflammatory cytokine modulation of peripheral nociceptive fibres. Recently, cytokine interactions in brain and spinal cord glia as well as dorsal root ganglia satellite glia have been identified important— in pain modulation. The result of these interactions is central and peripheral sensitisation of nociceptive processing. Additionally, new insights and the term ‘autoimmune pain’ have emerged through discovery of specific IgGs targeting the extracellular domains of antigens at nodal and synaptic structures, causing pain directly without inflammation by enhancing neuronal excitability. Other discovered IgGs heighten pain indirectly by T-cell-mediated inflammation or destruction of targets within the nociceptive pathways. Notable identified IgGs in pain include those against the components of channels and receptors involved in inhibitory or excitatory somatosensory synapses or their pathways: nodal and paranodal proteins (LGI1, CASPR1, CASPR2); glutamate detection (AMPA-R); GABA regulation and release (GAD65, amphiphysin); glycine receptors (GLY-R); water channels (AQP4). These disorders have other neurological manifestations of central/peripheral hyperexcitabability including seizures, encephalopathy, myoclonus, tremor and spasticity, with immunotherapy responsiveness. Other pain disorders, like complex regional pain disorder, have been associated with IgGs against β2-adrenergic receptor, muscarinic-2 receptors, AChR-nicotinic ganglionic α-3 receptors and calcium channels (N and P/Q types), but less consistently with immune treatment response. Here, we outline how the immune system contributes to development and regulation of pain, review specific IgG-mediated pain disorders and summarise recent development in therapy approaches. Biological agents to treat pain (anti-calcitonin gene-related peptide and anti-nerve growth factor) are also discussed.
Different neuroinflammatory profile in amyotrophic lateral sclerosis and frontotemporal dementia is linked to the clinical phase
Authors: Oeckl Patrick , Weydt Patrick , Steinacker Petra , Anderl-Straub Sarah , Nordin Frida , Volk Alexander E , Diehl-Schmid Janine , Andersen Peter M , Kornhuber Johannes , Danek Adrian , Fassbender Klaus , Fliessbach Klaus ,   German Consortium for Frontotemporal Lobar Degeneration, Jahn Holger , Lauer Martin , Müller Kathrin , Knehr Antje , Prudlo Johannes , Schneider Anja , Thal Dietmar R , Yilmazer-Hanke Deniz , Weishaupt Jochen H , Ludolph Albert C , Otto Markus
Published: September 2018

Objective

To investigate the role of neuroinflammation in asymptomatic and symptomatic amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) mutation carriers.

Methods

The neuroinflammatory markers chitotriosidase 1 (CHIT1), YKL-40 and glial fibrillary acidic protein (GFAP) were measured in cerebrospinal fluid (CSF) and blood samples from asymptomatic and symptomatic ALS/FTD mutation carriers, sporadic cases and controls by ELISA.

Results

CSF levels of CHIT1, YKL-40 and GFAP were unaffected in asymptomatic mutation carriers (n=16). CHIT1 and YKL-40 were increased in gALS (p<0.001, n=65) whereas GFAP was not affected. Patients with ALS carrying a CHIT1 polymorphism had lower CHIT1 concentrations in CSF (−80%) whereas this polymorphism had no influence on disease severity. In gFTD (n=23), increased YKL-40 and GFAP were observed (p<0.05), whereas CHIT1 was nearly not affected. The same profile as in gALS and gFTD was observed in sALS (n=64/70) and sFTD (n=20/26). CSF and blood concentrations correlated moderately (CHIT1, r=0.51) to weak (YKL-40, r=0.30, GFAP, r=0.39). Blood concentrations of these three markers were not significantly altered in any of the groups except CHIT1 in gALS of the Ulm cohort (p<0.05).

Conclusion

Our data indicate that neuroinflammation is linked to the symptomatic phase of ALS/FTD and shows a similar pattern in sporadic and genetic cases. ALS and FTD are characterised by a different neuroinflammatory profile, which might be one driver of the diverse presentations of the ALS/FTD syndrome.
Effects of myostatin on the mechanical properties of muscles during repeated active lengthening in the mouse
Authors: Satkunskiene Danguole , Ratkevicius Aivaras , Kamandulis Sigitas , Venckunas Tomas
Published: September 2018

The aim of the present study was to investigate how myostatin dysfunction affects fast and slow muscle stiffness and viscosity during severe repeated loading. Isolated extensor digitorum longus (EDL) and soleus muscles of young adult female mice of the BEH (dysfunctional myostatin) and BEH+/+ (functional myostatin) strains were subjected to 100 contraction–stretching loading cycles during which contractile and mechanical properties were assessed. BEH mice exhibited greater exercise-induced muscle damage, although the effect was muscle- and age-dependent and limited to the early phases of simulated exercise. The relative reduction of the EDL muscle isometric force recorded during the initial 10–30 loading cycles was greater in BEH mice than in BEH+/+ mice and exceeded that of the soleus muscle of either strain. The induced damage was associated with lower muscle stiffness. The effects of myostatin on the mechanical properties of muscles depend on muscle type and maturity.
Colored collapse models from the non-interferometric perspective
Authors: Carlesso Matteo , Ferialdi Luca , Bassi Angelo
Published: September 2018

Models of spontaneous wave function collapse describe the quantum-to-classical transition by assuming a progressive breakdown of the superposition principle when the mass of the system increases, providing a well-defined phenomenology in terms of a non-linearly and stochastically modified Schrödinger equation, which can be tested experimentally. The most popular of such models is the continuous spontaneous localization (CSL) model: in its original version, the collapse is driven by a white noise, and more recently, generalizations in terms of colored noises, which are more realistic, have been formulated. We will analyze how current non-interferometric tests bound the model, depending on the spectrum of the noise. We will find that low frequency purely mechanical experiments provide the most stable and strongest bounds.

Graphical abstract
A Stochastic Inventory Model for a Random Yield Supply Chain with Wholesale-Price and Shortage Penalty Contracts
Authors: Sato Kimitoshi , Yagi Kyoko , Shimazaki Masahito
Published: September 2018

This paper analyzes an infinite horizon, single-product, continuous-time inventory model with supply and demand risks to evaluate the impact of coordinating a production policy between a distributor and a supplier. We consider a wholesale-price contract and a shortage penalty contract as a coordination mechanisms in an inventory replenishment system. The demand process is described by a Brownian motion with drift, and this inventory model can be formulated as an impulse control problem with uncertain replenishment quantities. We show that under some assumptions, there exist optimal ordering and production policies. We also provide some numerical examples to investigate the effect of these coordination mechanisms on the expected costs and the optimal policies. The computational experiments reveal that (i) the production quantity in decentralized case is higher than that in the centralized case, (ii) the centralized approach strategy results in the lower joint total cost as compared with independent decision approaches, and (iii) the shortage penalty contract has a beneficial effect on the total cost to the entire supply chain in decentralized system.
CONVEX HULLS OF SIERPIŃSKI RELATIVES
Authors: TAYLOR T. D. , ROWLEY S.
Published: September 2018

This paper presents an investigation of the convex hulls of the Sierpiński relatives. These fractals all have the same fractal dimension but different topologies. We prove that the relatives have convex hulls with polygonal boundaries with at most 12 vertices. We provide a method for finding the convex hull of a relative using its scaling and symmetry properties and present examples. We also investigate the connectivity properties of certain classes of relatives with the same convex hulls.
FRACTAL ANALYSIS OF TEMPERATURE TIME SERIES FROM BATCH SUGARCANE CRYSTALLIZATION
Authors: CAMPOS-DOMINGUEZ ARMANDO , CEBALLOS-CEBALLOS YESSICA , VELAZQUEZ-CAMILO OSCAR , PUEBLA HÉCTOR , HERNANDEZ-MARTINEZ ELISEO
Published: September 2018

Batch crystallization is an important process in many industries, for example, fine chemicals, foods, and pharmaceuticals. Monitoring of the main process variables is essential for process understanding, diagnosis, and for product quality control. It is known that temperature has a critical effect on crystallization. Temperature measurements from crystallization systems display fluctuations with apparently random and complex behavior. Fractal analysis of complex time series has received significant attention in the last few years due to its capability for extraction of hidden useful information of the underlying phenomena behind the time-series complexity. In this work, the potential of fractal analysis of time series for diagnosis of industrial crystallization processes is investigated using temperature measurements from a typical batch sugarcane crystallization system. The crystallizer was operated at different cooling profiles, finding that fractal index is directly related to crystal mean diameter dynamics. Thus, we establish that fractal analysis is a simple and robust alternative for the characterization of batch crystallization.
Buckling of an Oscillating Rod Under Longitudinal Impact
Authors: Ilgamov Marat A.
Published: September 2018

The dynamics of a thin rod under the action of compressive force is considered. The compressive force increases abruptly and then remains constant. The compression of the rod is assumed to take place instantly throughout its length. The motion of the rod is studied, depending on the magnitude and time of action of the compressive force defined by the phase of the initial free oscillation of the rod. Only the initial stage of the process is investigated, for which the linear bending theory is valid. The friction forces are not taken into account. An essential relationship is shown to exist between the dynamics of the rod and the initial conditions determined by the phase of the bending oscillations at the instant of impact. Relatively weak impact leads to excitation of the bending oscillations. Rearrangement of harmonics develops with time under specified initial maximum deflection from a straight line and zero velocity. The fastest buckling takes place at some initial deflection with the velocity directed toward the increasing bend.
J+-Like invariants of periodic orbits of the second kind in the restricted three-body problem
Authors: Kim Joontae , Kim Seongchan
Published: September 2018

We determine three invariants: Arnold’s [Formula: see text]-invariant as well as [Formula: see text] and [Formula: see text] invariants, which were introduced by Cieliebak–Frauenfelder–van Koert, of periodic orbits of the second kind near the heavier primary in the restricted three-body problem, provided that the mass ratio is sufficiently small.
Windrose Planarity
Authors: Angelini Patrizio , Lozzo Giordano Da , Battista Giuseppe Di , Donato Valentino Di , Kindermann Philipp , Rote Günter , Rutter Ignaz
Published: September 2018

Given a planar graph
G
and a partition of the neighbors of each vertex
v
in four sets
v
↗
,
v
↖
,
v
↙
, and
v
↘
, the problem W
indrose
P
lanarity
asks to decide whether
G
admits a
windrose-planar drawing
, that is, a planar drawing in which (i) each neighbor
u
∈
v
↗
v
is above and to the right of
v
, (ii) each neighbor
u
∈
v
↖
is above and to the left of
v
, (iii) each neighbor
u
∈
v
↙
is below and to the left of
v
, (iv) each neighbor
u
∈
v
↘
is below and to the right of
v
, and (v) edges are represented by curves that are monotone with respect to each axis. By exploiting both the horizontal and the vertical relationship among vertices, windrose-planar drawings allow us to simultaneously visualize two partial orders defined by means of the edges of the graph.

Although the problem is
NP
-hard in the general case, we give a polynomial-time algorithm for testing whether there exists a windrose-planar drawing that respects a given combinatorial embedding. This algorithm is based on a characterization of the plane triangulations admitting a windrose-planar drawing. Furthermore, for any embedded graph with
n
vertices that has a windrose-planar drawing, we can construct one with at most one bend per edge and with at most 2
n
−5 bends in total, which lies on the 3
n
× 3
n
grid. The latter result contrasts with the fact that straight-line windrose-planar drawings may require exponential area.