bluuebunny/crossref_metadata_2025 huggingface dataset:
Phase II study of FOLFIRI + ramucirumab with recurrent colorectal cancer refractory to adjuvant chemotherapy with oxaliplatin / fluoropyrimidine (RAINCLOUD).
Authors: Sugimoto Naotoshi , Matsuda Chu , Hata Taishi , Satoh Taroh , Ikenaga Masakazu , Mizushima Tsunekazu , Murata Kohei , Ohue Masayuki , Doki Yuichiro , Mori Masaki
Published: January 2019

TPS882

Background: The RAISE study demonstrated the superiority of FOLFIRI + ramucirumab (Ram) to FOLFIRI in second-line metastatic colorectal cancer patients progressed after oxaliplatin, fluoropyrimidine with bevacizumab. But no prospective data is existed that the efficacy and toxicity of FOLFIRI + Ram pretreated oxaliplatin, fluoropyrimidine without an anti-angiogenesis therapy. Methods: RAINCLOUD study is a multicenter single-arm phase II trial. Key eligibility criteria is as follows: histologically or cytologically confirmed colorectal cancer, confirmed recurrent colorectal cancer, refractory to fluoropyrimidine, refractory or intolerant of oxaliplatin without pretreated anti-angiogenesis therapy, has measureable or non-measurable lesion, PS = 0 or 1, has adequate coagulation function, 20 years or older. Primary endpoint of this study is progression-free survival. Secondary endpoints are overall survival, time to treatment failure, response rate, disease control rate and safety. Patients receive FOLFIRI (irinotecan: 180 mg/m2, l-levofolinate: 200 mg/m2, bolus fluorouracil: 400mg/m2, and continuous fluorouracil: 2400 mg/m2) plus Ram (8 mg/kg) every two weeks until progression or the development of unacceptable toxicity. We hypothesized that threshold of PFS in FOLFIRI + Ram is 3.9 months and expected PFS is 6.9 months and designed to have an 80% power to detect clinically meaningful improvement in PFS at the one-sided significance level of 0.05, minimal patient registration number is 44 in order that power 1-β outperforms 0.8. Taking a few ineligibility patients and dropout patients into consideration, number of target patients is set to be 48. Study recruitment started on September 2017. The association of exploratory biomarker study will be planned. Clinical trial information: UMIN000028677.
The nationwide screening project on plasma angiogenesis-related mediators for treatment selection of optimal antiangiogenic inhibitors in metastatic colorectal cancer: GI-SCREEN CRC-Ukit.
Authors: Yuki Satoshi , Yamazaki Kentaro , Taniguchi Hiroya , Sunakawa Yu , Kawazoe Akihito , Kagawa Yoshinori , Kato Ken , Hara Hiroki , Denda Tadamichi , Oki Eiji , Moriwaki Toshikazu , Shiozawa Manabu , Satoh Taroh , Kawakami HIsato , Esaki Taito , Furuse Junji , Abe Yukiko , Nomura Shogo , Ohtsu Atsushi , Yoshino Takayuki
Published: January 2019

TPS885

Background: Antiangiogenic treatments are a proven useful tool to improve clinical outcomes in patients (pts) with metastatic colorectal cancer (mCRC). Recently, higher levels of vascular endothelial growth factor-D (VEGF-D) are a potential predictive biomarker for ramucirumab efficacy on overall and progression-free survival in mCRC (Tabernero J, et al. ESMO 2017). However, there are limited data on mCRC associating the efficacy of antiangiogenic therapy with angiogenesis-related mediators, such as VEGF family members and their receptors, and with dynamic transition among these mediators during clinical courses. In addition, immune-related factors such as interferon gamma (IFNγ) and transforming growth factor β1 (TGFβ1) may be associated with the regulation of angiogenesis. Methods: This prospective longitudinal study aims to investigate the association between plasma angiogenesis-related mediators and clinical outcomes in mCRC. The key eligibility criteria include pts with mCRC who will receive one of the following regimens: first-line chemotherapy plus bevacizumab, first-line chemotherapy plus anti-EGFR antibody (either cetuximab or panitumumab), second-line FOLFIRI plus ramucirumab, second-line FOLFIRI plus aflibercept, or second-line chemotherapy plus bevacizumab. Plasma is collected twice in pairs from all pts pre- and post-treatment. Comprehensive measurements of plasma angiogenesis-related mediators, such as placental growth factor (PlGF), hepatocyte growth factor (HGF), IL-6, IL-8, angiopoietin-2, neuropillin-1, tissue inhibitor of metalloproteinase-1 (TIMP-1), soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), thrombospondin-2 (TSP-2), osteopontin (OPN), sVEGFR-1, sVEGFR-2, sVEGFR-3, VEGF-A, VEGF-D, as well as key targets associated with immunotherapy such as IFNγ and TGFβ1 are analyzed in parallel by the multiplex assay with Luminex® technology. The target sample size is 1,000. This study was initiated in September 2017. Clinical trial information: UMIN000028616.
Glucose starvation triggers filamentous septin assemblies in an S. pombe septin-2 deletion mutant
Authors: Liu Minghua , Heimlicher Maria B. , Bächler Mirjam , Ibeneche-Nnewihe Chieze C. , Florin Ernst-Ludwig , Brunner Damian , Hoenger Andreas
Published: January 2019

Using correlative light and electron microscopy (CLEM), we studied the intracellular organization by of glucose-starved fission yeast cells (Schizosaccharomyces pombe) with regards to the localization of septin proteins throughout the cytoplasm. Thereby, we found that for cells carrying a deletion of the gene encoding septin-2 (spn2Δ), starvation causes a GFP-tagged version of septin-3 (spn3-GFP) and family members, to assemble into a single, prominent filamentous structure. It was previously shown that during exponential growth, spn2Δ cells form septin-3 polymers. However, the polymers we observed during exponential growth are different from the spn3p-GFP structure we observed in starved cells. Using CLEM, in combination with anti-GFP immunolabeling on plastic-sections, we could assign spn3p-GFP to the filaments we have found in EM pictures. Besides septin-3, these filamentous assemblies most likely also contain septin-1 as an RFP-tagged version of this protein forms a very similar structure in starved spn2Δ cells. Our data correlate phase-contrast and fluorescence microscopy with electron micrographs of plastic-embedded cells, and further on with detailed views of tomographic 3D reconstructions. Cryo-electron microscopy of spn2Δ cells in vitrified sections revealed a very distinct overall morphology of the spn3p-GFP assembly. The fine-structured, regular density pattern suggests the presence of assembled septin-3 filaments that are clearly different from F-actin bundles. Furthermore, we found that starvation causes substantial mitochondria fission, together with massive decoration of their outer membrane by ribosomes.
Development and validation of RdRp Screen, a crystallization screen for viral RNA-dependent RNA polymerases
Authors: Riccio Federica , Talapatra Sandeep K. , Oxenford Sally , Angell Richard , Mazzon Michela , Kozielski Frank
Published: January 2019

Members of the Flaviviridae family constitute a severe risk to human health. Whilst effective drugs have been developed against the hepacivirus HCV, no antiviral therapy is currently available for any other viruses, including the flaviviruses dengue (DENV), West Nile and Zika viruses. The RNA-dependent RNA polymerase (RdRp) is responsible for viral replication and represents an excellent therapeutic target with no homologue found in mammals. The identification of compounds targeting the RdRp of other flaviviruses is an active area of research. One of the main factors hampering further developments in the field is the difficulty in obtaining high-quality crystal information that could aid a structure-based drug discovery approach. To address this, we have developed a convenient and economical 96-well screening platform. We validated the screen by successfully obtaining crystals of both native DENV serotype 2 and 3 RdRps under several conditions included in the screen. In addition, we have obtained crystal structures of RdRp3 in complex with a previously identified fragment using both soaking and co-crystallization techniques. This work will streamline and accelerate the generation of crystal structures of viral RdRps and provide the community with a valuable tool to aid the development of structure-based antiviral design.
Transgenic and physiological mouse models give insights into different aspects of amyotrophic lateral sclerosis
Authors: De Giorgio Francesca , Maduro Cheryl , Fisher Elizabeth M. C. , Acevedo-Arozena Abraham
Published: January 2019

A wide range of genetic mouse models is available to help researchers dissect human disease mechanisms. Each type of model has its own distinctive characteristics arising from the nature of the introduced mutation, as well as from the specific changes to the gene of interest. Here, we review the current range of mouse models with mutations in genes causative for the human neurodegenerative disease amyotrophic lateral sclerosis. We focus on the two main types of available mutants: transgenic mice and those that express mutant genes at physiological levels from gene targeting or from chemical mutagenesis. We compare the phenotypes for genes in which the two classes of model exist, to illustrate what they can teach us about different aspects of the disease, noting that informative models may not necessarily mimic the full trajectory of the human condition. Transgenic models can greatly overexpress mutant or wild-type proteins, giving us insight into protein deposition mechanisms, whereas models expressing mutant genes at physiological levels may develop slowly progressing phenotypes but illustrate early-stage disease processes. Although no mouse models fully recapitulate the human condition, almost all help researchers to understand normal and abnormal biological processes, providing that the individual characteristics of each model type, and how these may affect the interpretation of the data generated from each model, are considered and appreciated.
The cell biology behind the oncogenic PIP3 lipids
Authors: Carrera Ana C. , Anderson Richard
Published: January 2019

The different mechanisms of phosphoinositide 3-kinase (PI3K) activation in cancer as well as the events that result in PI3K pathway reactivation after patient treatment with PI3K inhibitors was discussed on October 15–17th, 2018, in the medieval town of Baeza (Universidad Internacional de Andalucía, Spain) at the workshop entitled ‘The cell biology behind the oncogenic PIP3 lipids’. These topics and the data presented regarding cellular functions altered by PI3K deregulation, the cooperation of PI3K/PTEN mutations with other tumor drivers, and the lessons learned for PI3K-targeted therapy, are discussed below.
Lost in translation
Authors: Nachev Parashkev , Rees Geraint , Frackowiak Richard
Published: January 2019

Translation in cognitive neuroscience remains beyond the horizon, brought no closer by supposed major advances in our understanding of the brain. Unless our explanatory models descend to the individual level—a cardinal requirement for any intervention—their real-world applications will always be limited. Drawing on an analysis of the informational properties of the brain, here we argue that adequate individualisation needs models of far greater dimensionality than has been usual in the field. This necessity arises from the widely distributed causality of neural systems, a consequence of the fundamentally adaptive nature of their developmental and physiological mechanisms. We discuss how recent advances in high-performance computing, combined with collections of large-scale data, enable the high-dimensional modelling we argue is critical to successful translation, and urge its adoption if the ultimate goal of impact on the lives of patients is to be achieved.
Tissue and host species-specific transcriptional changes in models of experimental visceral leishmaniasis
Authors: Ashwin Helen , Seifert Karin , Forrester Sarah , Brown Najmeeyah , MacDonald Sandy , James Sally , Lagos Dimitris , Timmis Jon , Mottram Jeremy C , Croft Simon L. , Kaye Paul M.
Published: January 2019

Background: Human visceral leishmaniasis, caused by infection with Leishmania donovani or L. infantum, is a potentially fatal disease affecting 50,000-90,000 people yearly in 75 disease endemic countries, with more than 20,000 deaths reported. Experimental models of infection play a major role in understanding parasite biology, host-pathogen interaction, disease pathogenesis, and parasite transmission. In addition, they have an essential role in the identification and pre-clinical evaluation of new drugs and vaccines. However, our understanding of these models remains fragmentary. Although the immune response to Leishmania donovani infection in mice has been extensively characterized, transcriptomic analysis capturing the tissue-specific evolution of disease has yet to be reported.

Methods: We provide an analysis of the transcriptome of spleen, liver and peripheral blood of BALB/c mice infected with L. donovani. Where possible, we compare our data in murine experimental visceral leishmaniasis with transcriptomic data in the public domain obtained from the study of L. donovani-infected hamsters and patients with human visceral leishmaniasis. Digitised whole slide images showing the histopathology in spleen and liver are made available via a dedicated website, www.leishpathnet.org.

Results: Our analysis confirms marked tissue-specific alterations in the transcriptome of infected mice over time and identifies previously unrecognized parallels and differences between murine, hamster and human responses to infection. We show commonality of interferon-regulated genes whilst confirming a greater activation of type 2 immune pathways in infected hamsters compared to mice. Cytokine genes and genes encoding immune checkpoints were markedly tissue specific and dynamic in their expression, and pathways focused on non-immune cells reflected tissue specific immunopathology. Our data also addresses the value of measuring peripheral blood transcriptomics as a potential window into underlying systemic disease. 

Conclusions: Our transcriptomic data, coupled with histopathologic analysis of the tissue response, provide an additional resource to underpin future mechanistic studies and to guide clinical research.
Matrix transformations related to I-convergent sequences
Authors: Kolk Enno
Published: January 2019

Characterized are matrix transformations related to certain subsets of the space of ideal convergent sequences. Obtained here results are connected with the previous investigations of the author on some transformations defined by infinite matrices of bounded linear operators.
Boundedness of the L-index in a direction of entire solutions of second order partial differential equation
Authors: Bandura Andriy , Skaskiv Oleh
Published: January 2019

See PDF
On concircular curvature tensor in a Lorentzian α-Sasakian manifold with respect to the quarter-symmetric non-metric connection
Authors: Haseeb Abdul , Prasad Rajendra
Published: January 2019

In the present paper, some properties of concircular curvature tensor in a Lorentzian α-Sasakian manifold with respect to the quarter-symmetric non-metric connection have been studied.
Pedagogical technologies in modern higher education: possibility and necessity
Authors: Горач Николай , Gorach Nikolay , Карлина Ольга , Carlina Olga
Published: January 2019

In the article, from the standpoint of the system analysis of the issue, the characteristics of the main modern pedagogical technologies used in higher educational institutions of Russia are given, the features, principles, forms, methods and means of educational activity are derived. Ideally, new developments should take place gradually and naturally, excluding the crisis breaking of existing educational theories.
An assessment of early functional rehabilitation and hospital discharge in conventional versus robotic-arm assisted unicompartmental knee arthroplasty
Authors: Kayani B. , Konan S. , Tahmassebi J. , Rowan F. E. , Haddad F. S.
Published: January 2019

Aims

The objectives of this study were to compare postoperative pain, analgesia requirements, inpatient functional rehabilitation, time to hospital discharge, and complications in patients undergoing conventional jig-based unicompartmental knee arthroplasty (UKA) versus robotic-arm assisted UKA.

Patients and Methods

This prospective cohort study included 146 patients with symptomatic medial compartment knee osteoarthritis undergoing primary UKA performed by a single surgeon. This included 73 consecutive patients undergoing conventional jig-based mobile bearing UKA, followed by 73 consecutive patients receiving robotic-arm assisted fixed bearing UKA. All surgical procedures were performed using the standard medial parapatellar approach for UKA, and all patients underwent the same postoperative rehabilitation programme. Postoperative pain scores on the numerical rating scale and opiate analgesia consumption were recorded until discharge. Time to attainment of predefined functional rehabilitation outcomes, hospital discharge, and postoperative complications were recorded by independent observers.

Results

Robotic-arm assisted UKA was associated with reduced postoperative pain (p < 0.001), decreased opiate analgesia requirements (p < 0.001), shorter time to straight leg raise (p < 0.001), decreased number of physiotherapy sessions (p < 0.001), and increased maximum knee flexion at discharge (p < 0.001) compared with conventional jig-based UKA. Mean time to hospital discharge was reduced in robotic UKA compared with conventional UKA (42.5 hours (sd 5.9) vs 71.1 hours (sd 14.6), respectively; p < 0.001). There was no difference in postoperative complications between the two groups within 90 days’ follow-up.

Conclusion

Robotic-arm assisted UKA was associated with decreased postoperative pain, reduced opiate analgesia requirements, improved early functional rehabilitation, and shorter time to hospital discharge compared with conventional jig-based UKA.
Higher 30-day mortality associated with the use of intramedullary nails compared with sliding hip screws for the treatment of trochanteric hip fractures
Authors: Whitehouse M. R. , Berstock J. R. , Kelly M. B. , Gregson C. L. , Judge A. , Sayers A. , Chesser T. J.
Published: January 2019

Aims

The aim of this study was to investigate the association between the type of operation used to treat a trochanteric fracture of the hip and 30-day mortality.

Patients and Methods

Data on 82 990 patients from the National Hip Fracture Database were analyzed using generalized linear models with incremental case-mix adjustment for patient, non-surgical and surgical characteristics, and socioeconomic factors.

Results

The use of short and long intramedullary nails was associated with an increase in 30-day mortality (adjusted odds ratio (OR) 1.125, 95% confidence interval (CI) 1.040 to 1.218; p = 0.004) compared with the use of sliding hip screws (12.5% increase). If this were causative, it would represent 98 excess deaths over the four-year period of the study and one excess death would be caused by treating 112 patients with an intramedullary nail rather than a sliding hip screw.

Conclusion

There is a 12.5% increase in the risk of 30-day mortality associated with the use of an intramedullary nail compared with a sliding hip screw in the treatment of a trochanteric fractures of the hip.
Survivorship and long-term outcome of a consecutive series of 200 Scandinavian Total Ankle Replacement (STAR) implants
Authors: Clough T. , Bodo K. , Majeed H. , Davenport J. , Karski M.
Published: January 2019

Aims

We report the long-term clinical and radiological outcomes of a consecutive series of 200 total ankle arthroplasties (TAAs, 184 patients) at a single centre using the Scandinavian Total Ankle Replacement (STAR) implants.

Patients and Methods

Between November 1993 and February 2000, 200 consecutive STAR prostheses were implanted in 184 patients by a single surgeon. Demographic and clinical data were collected prospectively and the last available status was recorded for further survival analysis. All surviving patients underwent regular clinical and radiological review. Pain and function were assessed using the American Orthopaedic Foot and Ankle Society (AOFAS) hindfoot scoring system. The principal endpoint of the study was failure of the implant requiring revision of one or all of the components. Kaplan–Meier survival curves were generated with 95% confidence intervals and the rate of failure calculated for each year.

Results

A total of 84 patients (87 ankles) were alive by the end of this study. Of the surviving 84 patients (87 ankles; rheumatoid arthritis (RA), n = 40; OA, n = 47), 45 were women and 39 were men, with a mean age of 54 years (18 to 72 years) at the time of surgery. A total of 32 implants failed (16%), requiring revision surgery. The mean time to revision was 80 months (2 to 257). The implant survival at 15.8 years, using revision as an endpoint, was 76.16% (95% confidence interval (CI) 64.41 to 87.91). We found a steady but low decrease in survival over the study period. The mean AOFAS score improved from 28 (10 to 52) preoperatively to 61 (20 to 90) at long-term follow-up.

Conclusion

STAR prostheses in the United Kingdom have now been largely superseded by newer design TAAs, potentially with improved characteristics and surgical techniques. The long-term survivorship for the STAR prosthesis can provide a benchmark for these later designs of ankle arthroplasty.
Does having a rotator cuff repair prior to reverse total shoulder arthroplasty influence the outcome?
Authors: Erickson B. J. , Ling D. , Wong A. , Eno J. J. , Dines J. S. , Dines D. M. , Gulotta L. V.
Published: January 2019

Aims

The number of rotator cuff repairs that are undertaken is increasing. Reverse shoulder arthroplasty (RSA) is the procedure of choice for patients with rotator cuff arthropathy. We sought to determine whether patients who underwent rotator cuff repair and subsequent RSA had different outcomes compared with a matched control group who underwent RSA without a previous rotator cuff repair.

Patients and Methods

All patients with a history of rotator cuff repair who underwent RSA between 2000 and 2015 with a minimum follow-up of two years were eligible for inclusion as the study group. Outcomes, including the American Shoulder and Elbow Surgeons (ASES) scores, were compared with a matched control group of patients who underwent RSA without having previously undergone rotator cuff repair.

Results

The study group included 45 patients. Their mean age was 69 years (sd 8.6) and 27 patients (60%) were women. The mean ASES score improved from 43.1 to 76.6 two years postoperatively, and to 66.9 five years postoperatively. There was no significant difference between the outcomes at two years in the two groups (all p ≥ 0.05), although there was significantly more improvement in ASES scores in the control group (44.5 vs 33.4; p = 0.01). However, there was no significant difference between ASES scores at two and five years when baseline ASES scores were matched in the two groups (p = 0.42 at two years; p = 0.35 at five years).

Conclusion

Significant improvements in ASES scores were seen following RSA in patients who had previously undergone rotator cuff repair. They had higher baseline ASES scores than those who had not previously undergone this surgery. However, there was no significant difference in outcomes between the two groups, two years postoperatively. Previous rotator cuff repair does not appear to affect the early outcome after RSA adversely.
The critical size of a defect in the glenoid causing anterior instability of the shoulder after a Bankart repair, under physiological joint loading
Authors: Klemt C. , Toderita D. , Nolte D. , Di Federico E. , Reilly P. , Bull A. M. J.
Published: January 2019

Aims

Patients with recurrent anterior dislocation of the shoulder commonly have an anterior osseous defect of the glenoid. Once the defect reaches a critical size, stability may be restored by bone grafting. The critical size of this defect under non-physiological loading conditions has previously been identified as 20% of the length of the glenoid. As the stability of the shoulder is load-dependent, with higher joint forces leading to a loss of stability, the aim of this study was to determine the critical size of an osseous defect that leads to further anterior instability of the shoulder under physiological loading despite a Bankart repair.

Patients and Methods

Two finite element (FE) models were used to determine the risk of dislocation of the shoulder during 30 activities of daily living (ADLs) for the intact glenoid and after creating anterior osseous defects of increasing magnitudes. A Bankart repair was simulated for each size of defect, and the shoulder was tested under loading conditions that replicate in vivo forces during these ADLs. The critical size of a defect was defined as the smallest osseous defect that leads to dislocation.

Results

The FE models showed a high risk of dislocation during ADLs after a Bankart repair for anterior defects corresponding to 16% of the length of the glenoid.

Conclusion

This computational study suggests that bone grafting should be undertaken for an anterior osseous defect in the glenoid of more than 16% of its length rather than a solely soft-tissue procedure, in order to optimize stability by restoring the concavity of the glenoid.
Impact of Paternal Age at Conception on Human Health
Authors: Simard Mathieu , Laprise Catherine , Girard Simon L
Published: January 2019

BACKGROUND

The effect of maternal age at conception on various aspects of offspring health is well documented and often discussed. We seldom hear about the paternal age effect on offspring health, although the link is now almost as solid as with maternal age. The causes behind this, however, are drastically different between males and females.

CONTENT

In this review article, we will first examine documented physiological changes linked to paternal age effect. We will start with all morphological aspects of the testis that have been shown to be altered with aging. We will then move on to all the parameters of spermatogenesis that are linked with paternal age at conception. The biggest part of this review will focus on genetic changes associated with paternal age effects. Several studies that have established a strong link between paternal age at conception and the rate of de novo mutations will be reviewed. We will next discuss paternal age effects associated with telomere length and try to better understand the seemingly contradictory results. Finally, severe diseases that affect brain functions and normal development have been associated with older paternal age at conception. In this context, we will discuss the cases of autism spectrum disorder and schizophrenia, as well as several childhood cancers.

In many Western civilizations, the age at which parents have their first child has increased substantially in recent decades. It is important to summarize major health issues associated with an increased paternal age at conception to better model public health systems.
Male Contraceptive Development: Update on Novel Hormonal and Nonhormonal Methods
Authors: Long Jill E , Lee Min S , Blithe Diana L
Published: January 2019

BACKGROUND

Development of new methods of male contraception would address an unmet need for men to control their fertility and could increase contraceptive options for women. Pharmaceutical research and development for male contraception was active in the 1990s but has been virtually abandoned. The Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) has supported a contraceptive development program since 1969 and supports the majority of hormonal male contraceptive development. Nonhormonal methods are also in development but are at earlier stages.

CONTENT

Several hormonal male contraceptive agents have entered clinical trials. Single-agent products being evaluated include dimethandrolone undecanoate, 11β-methyl-nortestosterone dodecyl carbonate, and 7α-methyl-19-nortestosterone. A contraceptive efficacy trial of Nestorone® gel and testosterone gel in a single application will begin in 2018. Potential nonhormonal methods are at preclinical stages of development. Many nonhormonal male contraceptive targets that affect either sperm production or sperm function have been identified. Targeted pathways include the retinoic acid pathway, bromodomain and extraterminal proteins, and pathways for Sertoli cell–germ cell adhesion or sperm motility. Druggable targets include CatSper, the sperm Na+/K+-exchanger, TSSK, HIPK4, EPPIN, and ADAMs family proteins. Development of a procedure to reversibly block the vas deferens (initially developed in India in the 1980s) is undergoing early stage research in the US under the trade name Vasalgel™.

NICHD has supported the development of reversible male contraceptive agents. Other organizations such as the World Health Organization and the Population Council are pursuing male contraceptive development, but industry involvement remains dormant.
Osteoprotegerin is Higher in Sepsis Than in Noninfectious SIRS and Predicts 30-Day Mortality of SIRS Patients in the Intensive Care
Authors: Kemperman Hans , Schrijver Irene T , Roest Mark , Kesecioglu Jozef , van Solinge Wouter W , de Lange Dylan W
Published: January 2019

Background

Systemic inflammatory response syndrome (SIRS) is a complex disease involving multiple pathways and organs. Biomarkers reflecting these pathways and organ function could correlate with the severity of the disease. Osteoprotegerin (OPG), mainly known for its role in bone metabolism, is also involved in the immune and vascular system and is therefore an interesting biomarker to study in SIRS patients. In this prospective observational study, we investigated the correlation of plasma OPG concentrations, sepsis, and 30-day mortality of SIRS patients in the intensive care unit (ICU).

Methods

This observational, single-center, cohort study included 313 consecutive patients admitted to the ICU, with an anticipated stay of more than 48 h and SIRS on admission. Data from included patients were collected daily until discharge or death for a maximum of 10 days. Thirty-day mortality was retrospectively assessed. OPG concentrations were measured in the first 48 h after admission. The relation of OPG with no sepsis, sepsis, and septic shock was assessed with the Kruskal–Wallis test and the Mann–Whitney U-test. Cox proportional hazards regression was used to study OPG concentrations and 30-day mortality.

Results

OPG concentrations were higher in patients with sepsis and septic shock than in patients without sepsis. Furthermore, patients with OPG concentrations in the highest tertile at admission in the ICU have an increased risk of mortality within 30 days when compared to patients with OPG concentrations in the lowest and middle tertiles, independent of acute physiologic and chronic health evaluation (APACHE) and sequential organ failure assessment (SOFA) scores.

Conclusions

We show that OPG is a biomarker that correlates with sepsis and predicts mortality of SIRS patients in the ICU.
PENGARUH UMUR MASAK POLONG TERHADAP VIABILITAS DAN VIGOR BENIH BEBERAPA AKSESI BENGKUANG (Pachyrhizus erosus)
Authors: Krisnawati Ayda , Adie M Muchlish
Published: January 2019

Seed germination uniformity and simultaneity of yam bean was related to pod maturity. A total of ten accessions of yam bean was planted at Kendalpayak Research Station, Malang (Indonesia) from May to October 2016. Yam bean pods of each accession were harvested at three developmental stages, i.e. full-size green pods, yellow pods, and brown/black pods. The experiment was conducted using a completely randomized factorial design with three replications. The first factor was pod maturity and the second factor was yam bean accessions. Significant interactions between pod maturities with accessions were found on characters of epicotyl length, leaf length, leaf width, root dry weight, maximum growth potential, and germination rate at the 10th days of observation. The pod maturity at yellow stage gave the highest maximum growth potential and germination rate. The average germination rate of yellow pods was 8.15% per day which was, higher than those of green pods (3.83% per day) as well as black pods (3.73% per day). These yellow pods have optimal germination growth of compared to those of green as well as black pods. The practical implication of this research is the use of yellow pods as recommended seed source for yam bean cultivation.
KAJIAN POTENSI PRODUKSI AKAR ADVENTIF PAKIS POHON Cyathea contaminans (CYATHEACEAE) DI JAWA BARAT DAN SUMATERA UTARA
Authors: Wardani Wita
Published: January 2019

Study on production potential of adventitious root of the scaly tree fern Cyathea contaminans was conducted in six locations in West Java and North Sumatra using 20 m x 50 m sampling plot. Data recorded in the study consisted of population density, individual heights and diameter, volume of adventitious roots and environmental factors. The highest population density was found in a population that consisted of saplings with the height of less than 2 m tall. While population with adult plants has the density of 26–36 individual/100 m2. The wighest average volume of adventitious root per individuals was found in a population that dominated by adult stands and lies on a gentle slope at 108,760.70 cm3/individuals, while the lowest was in a population that consisted of saplings. The result statistical analysis showed that production of adventitious root were significantly different in different habitat. Moreover, there was positive correlation between trunk diameter and individual height with the volume of adventitious root, and between the diameter with individual height.
KEANEKARAGAMAN PALEM DI PULAU MENDANAU, BELITUNG
Authors: Andayani Deri , Nurtjahya Eddy , Rustiami Himmah
Published: January 2019

The study of palm in the Mendanau Island, Belitung was conducted in March 2017. There were 11 palm genera consisting of 14 species: Areca catechu, Calamus densiflorus, C. erinaceus, C. scipionum, Calamus sp., Caryota mitis, Daemonorops melanochaetes, Eleiodoxa conferta, Metroxylon sagu, Oncosperma tigillarium, Orania sylvicola, Pinanga malaiana, Plectocomia elongata, and Plectocomiopsis geminiflora. Based on the study of specimens deposited at Herbarium Bogoriense (BO), there were only four species recorded from Belitung Island, namely: Calamus erinaceus, C. scipionum, Eleiodoxa conferta, and Plectocomiopsis geminiflora. One species Calamus densiflorus is a new specimen collection for BO.
KESADARAN KELUARGA PETANI TERHADAP PENTINGNYA PENDIDIKAN FORMAL
Authors: _777 Syaefudin
Published: January 2019

Abstract. This study aims to: First, find out how the community awareness of farm families in the village of Pogungrejo to formal education. Secondly, to know what factors influence the awareness of the farmer's family in Pogungrejo Village towards formal education. This type of research is qualitative. Using the sociological approach of education. Data collection is obtained directly from informants through interviews, observation, and documentation. Data analysis techniques used are with data reduction, data display, data verification and affirmation of conclusions. Result of analysis from this research; First, the awareness of Pogungrejo village farmers is in a state of naive consciousness. They tend to be static in terms of awareness for highly educated. Education is still viewed as a diploma printing machine for eligibility in job search. They have not understood the full meaning of life as a whole person. Secondly, the factors that influence the awareness of Pogungrejo Village Farmer's family towards the importance of formal education are: Economic factors, awareness factor on education, Parents attention factor, Environmental factors, Facility education facilities, Religious factors, Factors of urbanization temptation.
AVALIAÇÃO IN VITRO DO FATOR DE PROTEÇÃO SOLAR (FPS) DE COSMÉTICOS FOTOPROTETORES MANIPULADOS
Authors: Secco Gabriela Gislaine , Beltrame Betina Montanari , Schwanz Melissa
Published: January 2019

Visando reduzir os efeitos nocivos causados na pele pela radiação solar, a utilização de fotoprotetores é uma realidade. Com base na importância do tema, o objetivo dessa pesquisa foi determinar experimentalmente, por espectrofotometria na região do ultravioleta, o fator de proteção solar (FPS) e, ainda, avaliar características macroscópicas e físico-químicas de fotoprotetores manipulados rotulados FPS 30, além de evidenciar a possibilidade de determinação do FPS pela técnica in vitro para controle da qualidade em as farmácias magistrais. Os resultados mostraram que as formulações se apresentaram visivelmente homogêneas, de coloração normal, odor característico e toque agradável. O pH manteve-se na faixa de 6,30 a 7,66. No teste de estabilidade por centrifugação uma das amostras apresentou leve evidência de falta de homogeneidade e as demais não apresentaram qualquer alteração em relação ao seu aspecto original. Quanto ao FPS in vitro, uma das formulações em estudo obteve valor acima do rotulado e as demais obtiveram FPS inferiores aos declarados nos rótulos. A avaliação in vitro utilizada no trabalho pode contribuir para a determinação e controle de produtos manipulados, por ser uma técnica confiável e de fácil execução.
Spending Behavior of Thai Tourists in Dan Sai District, Loei province, Thailand: Seemingly Unrelated Regression Estimation Analysis
Authors: NONTHAPOT Sakkarin , WATTANAKUL Thanet , WANGKEEREE Kitiya
Published: January 2019

The purpose of this study is to investigate the spending behavior of Thai tourists in Dan Sai District, Loei province, Thailand by applying the Almost Ideal Demand System (AIDS) model. The analysis was conducted by employing Seemingly Unrelated Regression Estimation (SURE). A questionnaire was used to collect data and 400 samples were collected. The results revealed that the price factor influences the cost of accommodation on other expenses, food and beverage expenses on other expenses and travel expenses on other expenses while the revenue factor influences travel costs on other expenses and the cost of souvenirs on other expenses. The results of the study show that there should be measures to stimulate tourist spending using price strategy to encourage tourists to spend more, and marketing strategies should be used to encourage high-income tourists to spend in Dan Sai District.
Analysis of Community Based Tourism Development to Increase SME Performance and Welfare Level. Case Study in West Sumatra
Authors: SUPRIYADI Edy , IHA Haryani Hatta , DJAMIL Achmad , DHARMA Putra
Published: January 2019

This study evaluates the perception of developing community-based tourism (CBT) as a strategy of developing community-based tourist destination in West Sumatra located in solok and Pesisir Selatan district. This study aims to examine the relationship between independent variables such as Infrastructure, Social Capital Potential, Commitment, government policy with dependent variable Development of MSME and Public Welfare with intermediary variables consisting of Collaboration, CBT tourism destination. Population is all tourists in West Sumatra province and samples taken in several the owner of SME areas using multistage cluster purposive sampling method. Statistical analysis using SEM Structural Equation Modelling analysis with PLS software. The results are obtained that Infrastructure, commitment, Social Networking, the role of government have a positive and significant influence on collaboration. There is sufficient mediation to play a role of the collaboration component that links between Infrastructure, Commitment, Social Networking, the role of governments with CBT. The development of CBT has an effect on creating job opportunities and developing SMEs.
Detailization of the Facial Conditions for Sedimentation of the 〖Yu〗_1^2 Productive Layer with the Purpose of Specificating Features of the Geological Structure
Authors: ALEKSANDROV SorinVadim M. , MOROZOV Alexander V. , POPOV Ivan P. , LEBEDEVA Rushania G. , BULGAKOVA Irina A.
Published: January 2019

The detailed characterization of the environmental conditions of sedimentation of the  productive formation makes it possible to refine the features of the geological structure. The authors carried out a detailed lithologic-facial analysis of the deposits of the Yu12 productive formation at one of the deposits located in the southeastern part of the West Siberian oil and gas basin. Detailed lithologic-facial schemes were constructed that reflect the spatial distribution of the main permeable bodies, considering the forecast of the distribution of promising reservoir rocks in zones not covered by drilling. The well test results confirm the adopted model of sedimentary facies distribution over the area of the deposit. The proposed conceptual model was used to construct a three-dimensional facial model of the deposit. Thus, a detailed lithologic-facial analysis of the core and forms of the GIS curves showed that deposits of the  stack accumulated in coastal-marine sedimentation environments – "marshes" and "watts", repeatedly replacing each other vertically.
Perfecting the Cluster Development in the Regional Dairy Products Subcomplex of the Russian Agro-Industrial Complex
Authors: ZAVOROTIN E. F. , YURKOVA M. S. , SERDOBINTSEV D. V. , LIKHOVTSOVA E. A. , VOLOSHCHUK L. A.
Published: January 2019

A considerable increase in prices for raw milk in Russia in 2013-2015 and the support for beginner farmers had an impact on improving the intensity of production in the dairy cattle breeding. However, due to the high share of the population’s households in the structure of milk production (about 45%) and its low marketability (about 34%), there is a deficit and dependence on import. At the same time, the tempos of the growth of prices for raw milk cannot provide producers with development due to the delay of cost increase, reduction of the consumer demand and high price competition with exporters from Belarus. All this is a consequence of the lack of an efficient system of re-allocating the created value between sectors of the dairy products subcomplex of the agro-industrial complex of the Russian Federation, the servicing area, and trade. The creation of agro-industrial clusters in regions will solve such problems as the non-participation of the state in regulating the price formation on the milk and dairy products market, the lack of a transparent mechanism to stipulate the retail price for dairy products, infrastructure problems, innovative and investment development, etc. The research allowed us to substantiate the possibility of creating a dairy products cluster in the Saratov Region. Forming a logistic model and comparing algorithms of commodity circulation, it was determined that functioning of the cluster would exclude duplication of production and marketing functions and reduce the total costs by more than 40% on average. Prerequisites will be made to increase production volumes, to develop the infrastructure of the region and rural areas, and to increase the population’s employment, which will make up a huge social and economic effect at the minimal cost.
Measuring Dairy Farm Efficiency in the Republic of Kazakhstan
Authors: BALKIBAYEVA Aida , AIDYNOV Zein , ORAZBAYEVA Ayagoz , SHEIKO Yuliya , AIKUPESHEVA Dina
Published: January 2019

Study was conducted in the area of comparative dairy efficiency and finding the most effective farms that can be used by less effective farms and new dairy farms to increase their outputs and use inputs in more productive ways. We used the data of dairy farms for 2015 provided by National Committee on Statistics of Kazakhstan upon our request to perform this research and applied Data Envelope Analysis (DEA).  The closest to the efficiency boundary was the dairy farm with a value of 0.66 (milk production 3 573 tons per year with the following top expenses: feed $400K; depreciation $200K and salary $142.424). Based on super-efficiency factors farm No 3 which produced 762,1 tons of milk  per year with the cost closest to min mean was found as the most effective one among others. The least efficient was farm No 1 produced the most amounts of milk but with higher than average expenses.

Based on the literature-based review the concept of dairy efficiency was developed, showing the linkage between inputs such as feed, salary, depreciation, energy and others.

Further analysis can show the geographic and climatic similarity or the identity of the management system of reference, distribution of feed and tied inefficient pre-regions. Proceeding from this, it is possible to develop and make management decisions that allow inefficient enterprises to become effective companies
Formation of Resource Potential of Agrarian Enterprises on the Principles of Ecological and Economic Security
Authors: KHROMUSHYNA Lyudmyla , KONIEVA Iryna , SKRYPNYK Yuriy , SHALYHINA Iryna
Published: January 2019

In this article the authors have substantiated the formation of the resource potential of agrarian enterprises on the basis of compliance with the requirements of ecological and economic security. The authors define the concept of "resource potential of an agrarian enterprise" and considered the constituent structure of resource potential. The definition of "ecological and economic security of activity of agrarian enterprises" was given. It is determined that the establishment of ecological and economic security in the activities of agrarian enterprises will promote the production of organic products, will create conditions for increasing the competitiveness of enterprises. The study of the connection and interaction of elements of the resource potential of agrarian enterprises with the constituent elements of ecological and economic security was carried out. As a result of the study, the scheme of formation of resource potential of agrarian enterprises based on the requirements of ecological and economic security was proposed and grounded. The main problems, which hinder the formation of ecologically safe economic development of agrarian enterprises, and, accordingly, have a negative influence on the formation of their resource potential. The methodological basis of the study was the dialectic method of cognition and the systematic approach to the study of the problem of the formation of resource potential. In carrying out the research were applied general scientific methods: abstract-logical, monographic, generalization.
Diversity of Mangrove Plant for Support Ecotourism Activities in Nature Conservation Forum Putri Menjangan, Pejarakan Buleleng-Bali
Authors: GINANTRA I Ketut , SUASKARA Ida Bagus Made , JONI Martin
Published: January 2019

This study aims to identify the species of mangrove constituents and determine the zonation of the growing community of mangrove plants from the seaward to the landward zone, of the Nature Conservation Forum (NCF) Putri Menjangan coastal Pejarakan village Buleleng from July to October 2017. Identification of mangrove plant species based on the following characteristics: habitus, root type, fruit shape, inflorescence, leaf shape and leaf arangement. Zoning of mangrove grown is determined from vegetation analysis conducted in 3 zones (front zone, middle zone and back zone) with quadrat method, the area of each square is 20 m x 20 m. Parameters specified in each kwadrat are the density, dominance and frequency of presence of each species. Zoning of mangrove community is determined based on the important value of mangrove plant species. The diversity of the mangrove community is calculated by the Shanon-Wiener Diversity Index. The results of the study identified 13 species of true mangrove plants (mangrove) and 14 mangrove mangrove associates. The dominant species are Sonneratia alba (important value / iv is 98.19), Lumnitzera racemosa (iv. is 40.75), Rhizophora apiculata (iv.is 35.53), Rhizophora mucronata (iv. 33.02), Ceriops decandra (iv.23.61) and Avicennia marina (iv. 22.22). The diversity index of mangrove species (H) is 2.07, then it is considered good. The pattern of growing mangrove plants in coastal Pejarakan Buleleng, in general follow the natural pattern of mangrove zonation. Typical characteristics and patterns of growing mangrove zonation become interesting attractions and reference for mangrove area managers in ecotourism development and efforts to conserve mangrove forests.