bluuebunny/crossref_metadata_2025 huggingface dataset:
The ZP Framework and Effective Leadership Behaviour in Problematic, Non-Problematic and Issue-Ridden Situations
Authors: Khandekar Rajendra
Published: September 2019

A review of leadership literature reveals three patterns. First, all leadership theories address problematic situations. Second, leadership theories address problems at increasingly complex levels of social systems from individual to relationships to groups to organizations and finally societies. Third, leadership theories imply that an effective leader identifies, flexibly prioritizes and acts accordingly on task and emotional problems confronting the social system to achieve goals. This paper reframes the concept of ‘situation’ using the Zeroth P (ZP) framework to integrate the above three patterns. The ZP framework provides a way to sort situations into four different types of problematic and non-problematic situations. It is proposed that each type of situation requires different types of leader behaviours. The proposed appropriate combinations are: Celebratory behaviour in a non-problematic situation when what is happening is what should be happening; Boundary-clarifying behaviour, in a non-problematic situation where nothing is happening that should not be happening; Rebellious behaviour when what is happening should not be happening; and Visionary/Innovative behaviour when the leader envisions a better world or situation that does not yet exist, but should exist. Application of the framework is illustrated at the individual and group levels, and research avenues are pointed out.
Leveraging Multiple Machine-Learning Techniques to Predict Major Life Outcomes from a Small Set of Psychological and Socioeconomic Variables: A Combined Bottom-up/Top-down Approach
Authors: Altschul Drew M.
Published: September 2019

Predicting longitudinal outcomes from thousands of variables across multiple waves provides impressive opportunities to identify variables of importance, but what is the most efficient way to carry out such analyses on hundreds or thousands of variables? As part of the Fragile Families Challenge, a series of analyses were conducted that aimed at identifying a few reliable, important variables, primarily with machine-learning approaches given minimal oversight. Using generalized boosted models, random forests, and elastic net regression models, these analyses identified a consistent set of psychological and socioeconomic factors that yielded strong prediction scores in generalized linear models. These results demonstrate that relatively simple models fitted to the Fragile Families data can generate predictions that perform close to state-of-the-art predictive models.
Data-Specific Functions: A Comment on Kindel et al.
Authors: Fisher Jacob C.
Published: September 2019

In this issue, Kindel et al. describe a new approach to managing survey data in service of the Fragile Families Challenge, which they call “treating metadata as data.” Although the approach they present is a good first step, a more ambitious proposal could improve survey data analysis even more substantially. The author recommends that data collection efforts distribute an open-source set of tools for working with a particular data set the author calls data-specific functions. The goal of these functions is to codify best practices for working with the data in a set of functions for commonly used statistical software. These functions would be jointly developed by the users and distributers of the data. Building such functions would both shorten the learning curve for new users and improve the quality of the data, by making tacit knowledge about problems with the data explicit and easy to act on.
Branch Retinal Artery Occlusion Following Intravitreal Injection of Methotrexate for the Treatment of Primary Vitreoretinal Lymphoma
Authors: Venkat Arthi G. , Karthik Naveen , Lowe Ashley , Sharma Sumit
Published: September 2019

Purpose:

This paper reports a case of an older white woman presenting with recalcitrant bilateral vitreoretinal inflammation that was ultimately proven to be primary vitreoretinal lymphoma by vitreous biopsy who subsequently developed a branch retinal artery occlusion (BRAO) following an intravitreal injection of methotrexate.

Methods:

Case summary.

Results:

The patient was treated with serial intravitreal methotrexate injections and subsequently developed a BRAO immediately following her seventh injection.

Conclusions:

A full systemic evaluation to rule out other causes of the BRAO was negative and given the timing of her symptoms after the injection it was determined that the BRAO was most likely realted to the intravitreal methotrexate injection.
Distinct immune composition in lymph node and peripheral blood of CLL patients is reshaped during venetoclax treatment
Authors: de Weerdt Iris , Hofland Tom , de Boer Renate , Dobber Johan A. , Dubois Julie , van Nieuwenhuize Denise , Mobasher Mehrdad , de Boer Fransien , Hoogendoorn Mels , Velders Gerjo A. , van der Klift Marjolein , Remmerswaal Ester B. M. , Bemelman Frederike J. , Niemann Carsten U. , Kersting Sabina , Levin Mark-David , Eldering Eric , Tonino Sanne H. , Kater Arnon P.
Published: September 2019

Morbidity and mortality due to immunosuppression remain among the foremost clinical challenges in chronic lymphocytic leukemia (CLL). Although immunosuppression is considered to originate within the lymph node (LN) microenvironment, alterations in T and natural killer (NK) cells have almost exclusively been studied in peripheral blood (PB). Whereas chemoimmunotherapy further deteriorates immune function, novel targeted agents like the B-cell lymphoma 2 inhibitor venetoclax potentially spare nonmalignant lymphocytes; however, the effects of venetoclax on nonleukemic cells have not been explored. We address these unresolved issues using a comprehensive analysis of nonmalignant lymphocytes in paired LN and PB samples from untreated CLL patients, and by analyzing the effects of venetoclax-based treatment regimens on the immune system in PB samples from previously untreated and relapsed/refractory patients. CLL-derived LNs contained twice the amount of suppressive regulatory T cells (Tregs) and CLL supportive follicular T helper (Tfh) cells compared with PB. This was accompanied by a low frequency of cytotoxic lymphocytes. The expression of PD-1 by CD8+ T cells was significantly higher in LN compared with PB. Venetoclax-based treatment led to deep responses in the majority of patients, but also to decreased absolute numbers of B, T, and NK cells. Tfh cell, Treg, and PD-1+ CD8+ T cell numbers were reduced more than fivefold after venetoclax-based therapy, and overproduction of inflammatory cytokines was reduced. Furthermore, we observed restoration of NK cell function. These data support the notion that the immunosuppressive state in CLL is more prominent within the LN. Venetoclax-based regimens reduced the immunosuppressive footprint of CLL, suggesting immune recovery after the elimination of leukemic cells.
Decoding the role of SOD2 in sickle cell disease
Authors: Dosunmu-Ogunbi Atinuke M. , Wood Katherine C. , Novelli Enrico M. , Straub Adam C.
Published: September 2019

Sickle cell disease (SCD) is an inherited hemoglobinopathy caused by a single point mutation in the β-globin gene. As a consequence, deoxygenated hemoglobin polymerizes triggering red blood cell sickling and hemolysis, vaso-occlusion, and ischemia/reperfusion. Allied to these pathologies is the overproduction of reactive oxygen species driven by hemoglobin Fenton chemistry and peroxidase reactions as well as by secondary activation of vascular oxidases, including NAD(P)H oxidase and xanthine oxidase. In addition, hypoxia, produced by sickle red blood cell occlusion, disrupts mitochondrial metabolism and generates excess superoxide through electron leak from the mitochondrial respiratory chain. Superoxide dismutase 2 (SOD2) is a mitochondrial-specific antioxidant enzyme that dismutates superoxide to hydrogen peroxide, which is then converted to water by catalase and glutathione peroxidase. In SCD, the antioxidant defense system is significantly diminished through decreased expression and activity levels of antioxidant enzymes, including superoxide dismutase, catalase, and glutathione peroxidase. From a translational perspective, genetic variants including a missense variant in SOD2 (valine to alanine at position 16) are present in 45% of people with African ancestry and are associated with increased sickle complications. While it is known that there is an imbalance between oxidative species and antioxidant defenses in SCD, much more investigation is warranted. This review summarizes our current understanding of antioxidant defense systems in SCD, particularly focused on SOD2, and provides insight into challenges and opportunities as the field moves forward.
Reticulocyte and red blood cell deformation triggers specific phosphorylation events
Authors: Moura Pedro L. , Lizarralde Iragorri Maria A. , Français Olivier , Le Pioufle Bruno , Dobbe Johannes G. G. , Streekstra Geert J. , El Nemer Wassim , Toye Ashley M. , Satchwell Timothy J.
Published: September 2019

The capacity to undergo substantial deformation is a defining characteristic of the red blood cell (RBC), facilitating transit through the splenic interendothelial slits and microvasculature. Establishment of this remarkable property occurs during a process of reticulocyte maturation that begins with egress through micron-wide pores in the bone marrow and is completed within the circulation. The requirement to undertake repeated cycles of deformation necessitates that both reticulocytes and erythrocytes regulate membrane-cytoskeletal protein interactions in order to maintain cellular stability. In the absence of transcriptional activity, modulation of these interactions in RBCs is likely to be achieved primarily through specific protein posttranslational modifications, which at present remain undefined. In this study, we use high-throughput methods to define the processes that underlie the response to deformation and shear stress in both reticulocytes and erythrocytes. Through combination of a bead-based microsphiltration assay with phosphoproteomics we describe posttranslational modification of RBC proteins associated with deformation. Using microsphiltration and microfluidic biochip-based assays, we explore the effect of inhibiting kinases identified using this dataset. We demonstrate roles for GSK3 and Lyn in capillary transit and maintenance of membrane stability following deformation and show that combined inhibition of these kinases significantly decreases reticulocyte capacity to undergo repeated deformation. Finally, we derive a comprehensive and integrative phosphoproteomic dataset that provides a valuable resource for further mechanistic dissection of the molecular pathways that underlie the RBC’s response to mechanical stimuli and for the study of reticulocyte maturation.
Using wearables and self-management apps in patients with COPD: a qualitative study
Authors: Wu Robert C. , Ginsburg Shiphra , Son Tatiana , Gershon Andrea S.
Published: September 2019

Background

Technology such as wearable technology and self-management applications could improve the care of patients with chronic obstructive pulmonary disease (COPD) by real-time continuous monitoring, early detection of COPD and improved self-management. However, patients have not been willing to use technology when it is too difficult to use, interferes with their daily lives or threatens their identity, independence and self-care.

Methods

We conducted a qualitative study to determine what patients with COPD would like to see in a wearable device and a mobile application to help manage their condition. Semi-structured interviews were conducted, recorded and transcribed. Thematic analysis was used to identify themes and concepts.

Results

We interviewed 14 people with COPD with an average age of 69 years. Participants perceived that the technology could improve their ability to manage their condition both in daily life and during exacerbations by connecting how they feel and by knowing their oxygen saturation, heart rate and activity. The technology may help them address feelings of fear and panic associated with exacerbations and may provide reassurance and connectedness. Some people with COPD wanted their healthcare providers to have access to their data, while others were concerned about inundating them with too much information. Of note, people wanted to maintain control of the information; to make connections with the data, but also in order to be alerted when a possible exacerbation occurs.

Conclusion

Patients perceived significant potential for wearables and apps to help manage their condition.
Comparison of intrapleural use of urokinase and tissue plasminogen activator/DNAse in pleural infection
Authors: Bédat Benoît , Plojoux Jérôme , Noel Jade , Morel Anna , Worley Jonathan , Triponez Frédéric , Karenovics Wolfram
Published: September 2019

Fibrinolysis can be used to improve fluid drainage in pleural infection. Treatment with either urokinase or tissue plasminogen activator (t-PA) in association with DNAseviaa chest tube has been effective at reducing the need for surgery. This study is the first to compare the efficacy of these two treatments.

We performed a single-centre, controlled, prospective cohort study. All individuals with pleural infection admitted to our hospital between January 2014 and December 2017 who were treated with antibiotics, a chest tube and fibrinolysis were included in this study. The rate of additional procedure requirements (additional chest tube or surgery) after initial fibrinolysis, complications, costs, and radiological and biological outcomes were analysed.

Among the 93 patients included in this study, 34% required additional procedures after an initial fibrinolysis, including 21% who received an additional chest tube and 13% who underwent thoracoscopy. The need for additional procedures arose due to presence of multiple pleural collections (p=0.01) and was associated with the use of large-bore drain (p=0.01). The success rate of fibrinolysis was not significantly different between urokinase and t-PA/DNAse (p=0.35). The differences in drainage duration and in length of hospital stay were not significant either (p=0.05 and p=0.12, respectively). Treatment with t-PA/DNAse was cheaper (p=0.04) but was associated with a higher rate of haemothorax (p=0.002).

In conclusion, treatment with urokinase is safer and equally effective when compared with treatment with t-PA/DNAse.
Development and validation of the comprehensive assessment scale for chemotherapy–induced peripheral neuropathy in survivors of cancer
Authors: Kanda K. , Fujimoto K. , Mochizuki R. , Ishida K. , Lee B.
Published: September 2019

Background

Appropriate assessment is essential for the management of chemotherapy-induced peripheral neuropathy (CIPN), an intractable symptom that cannot yet be palliated, which is high on the list of causes of distress for cancer patients. However, objective assessment by medical staff makes it easy to underestimate the symptoms and effects of CIPN in cancer survivors. As a result, divergence from subjective evaluation of cancer survivors is a significant problem. Therefore, there is an urgent need to develop a subjective scale with high accuracy and applicability that reflects the experiences of cancer patients. We developed a comprehensive assessment scale for CIPN in cancer survivors, named the Comprehensive Assessment Scale for Chemotherapy-Induced Peripheral Neuropathy in Survivors of Cancer (CAS-CIPN), and demonstrated its reliability and validity.

Methods

We developed a questionnaire based on qualitative studies of peripheral neuropathy in Japanese cancer patients and literature review. Twelve cancer experts confirmed the content validity of the questionnaire. A draft version comprising 40 items was finalized by a pilot test on 100 subjects. The participants in the present study were 327 Japanese cancer survivors. Construct validity was determined by factor analysis, and internal validity by confirmation factor analysis and Cronbach’s α.

Results

Factor analysis showed that the structure consisted of 15 items in four dimensions: “Threatened interference in daily life by negative feelings”, “Impaired hand fine motor skills”, “Confidence in choice of treatment/management,” and “Dysesthesia of the palms and soles.” The CAS-CIPN internal consistency reliability was 0.826, and the reliability coefficient calculated using the Spearman-Brown formula [q = 2r/(1 + r)] was 0.713, confirming high internal consistency and stability. Scores on this scale were strongly correlated with Gynecologic Oncology Group-Neurotoxicity scores (r = 0.714, p < 0.01), confirming its criterion-related validity.

Conclusions

The CAS-CIPN is an assessment tool with high reliability and validity for the comprehensive evaluation of CIPN in cancer survivors. The CAS-CIPN is simple to use, and can be used by medical professionals for appropriate situational assessment and intervention.
Hospitalization at the end of life among nursing home residents with dementia: a systematic review
Authors: Hoffmann Falk , Strautmann Anke , Allers Katharina
Published: September 2019

Background

Half of nursing home residents (NHR) suffer from dementia. End-of-life hospitalizations are often burdensome in residents with dementia. A systematic review was conducted to study the occurrence of hospitalizations at the end of life in NHR with dementia and to compare these figures to NHR without dementia.

Methods

A systematic literature search in MEDLINE, CINAHL and Scopus was conducted in May 2018. Studies were included if they reported proportions of in-hospital deaths or hospitalizations of NHR with dementia in the last month of life. Two authors independently selected studies, extracted data, and assessed quality of studies.

Results

Nine hundred forty-five citations were retrieved; 13 studies were included. Overall, 7 studies reported data on in-hospital death with proportions ranging between 0% in Canada and 53.3% in the UK. Studies reporting on the last 30 days of life (n = 8) varied between 8.0% in the Netherlands and 51.3% in Germany. Two studies each assessed the influence of age and sex. There seem to be fewer end-of-life hospitalizations in older age groups. The influence of sex is inconclusive. All but one study found that at the end of life residents with dementia were hospitalized less often than those without (n = 6).

Conclusions

We found large variations in end-of-life hospitalizations of NHR with dementia, probably being explained by differences between countries. The influence of sex and age might differ when compared to residents without dementia. More studies should compare NHR with dementia to those without and assess the influence of sex and age.

Trial registration

PROSPERO registration number CRD42018104263.
Characterizing an engineered carotenoid-producing yeast as an anti-stress chassis for building cell factories
Authors: Liu Hsien-Lin , Chang Jui-Jen , Thia Caroline , Lin Yu-Ju , Lo Shou-Chen , Huang Chieh-Chen , Li Wen-Hsiung
Published: September 2019

Background

A microorganism engineered for non-native tasks may suffer stresses it never met before. Therefore, we examined whether a Kluyveromyces marxianus strain engineered with a carotenoid biosynthesis pathway can serve as an anti-stress chassis for building cell factories.

Results

Carotenoids, a family of antioxidants, are valuable natural products with high commercial potential. We showed that the free radical removal ability of carotenoids can confer the engineered host with a higher tolerance to ethanol, so that it can produce more bio-ethanol than the wild type. Moreover, we found that this engineered strain has improved tolerance to other toxic effects including furfurals, heavy metals such as arsenate (biomass contaminant) and isobutanol (end product). Furthermore, the enhanced ethanol tolerance of the host can be applied to bioconversion of a natural medicine that needs to use ethanol as the delivery solvent of hydrophobic precursors. The result suggested that the engineered yeast showed enhanced tolerance to ethanol-dissolved hydrophobic 10-deacetylbaccatin III, which is considered a sustainable precursor for paclitaxel (taxol) bioconversion.

Conclusions

The stress tolerances of the engineered yeast strain showed tolerance to several toxins, so it may serve as a chassis for cell factories to produce target products, and the co-production of carotenoids may make the biorefinary more cost-effective.
A systematic approach to study the pH-dependent release, productivity and product specificity of dextransucrases
Authors: Schmid Jonas , Bechtner Julia , Vogel Rudi F. , Jakob Frank
Published: September 2019

Background

Dextransucrases are extracellular enzymes, which catalyze the formation of α-1→6-linked glucose polymers from sucrose. These enzymes are exclusively expressed by lactic acid bacteria, which commonly acidify the extracellular environment due to their physiology. Dextransucrases are thus confronted with steadily changing reaction conditions in regards to the environmental pH, which can further affect the amount of released dextransucrases. In this work, we studied the effect of the environmental pH on the release, the productivity and the product specificity of the dextransucrase expressed byLactobacillus(L.)hordeiTMW 1.1822. Dextransucrases were recovered as crude extracts at pH 3.5–pH 6.5 and then again used to produce dextrans at these pH values. The respectively produced dextran amounts and sizes were determined and the obtained results finally systematically correlated.

Results

Maximum dextran amounts were produced at pH 4.0 and pH 4.5, while the productivity of the dextransucrases significantly decreased at pH 3.5 and pH 6.5. The distribution of dextran amounts produced at different pH most likely reflects the pH dependent activity of the dextransucrases released byL. hordei, since different transglycosylation rates were determined at different pH using the same dextransucrase amounts. Moreover, similar hydrolysis activities were detected at all tested conditions despite significant losses of transglycosylation activities indicating initial hydrolysis prior to transglycosylation reactions. The molar masses and rms radii of dextrans increased up to pH 5.5 independently of the stability of the enzyme. The gelling properties of dextrans produced at pH 4.0 and pH 5.5 were different.

Conclusions

The presented methodological approach allows the controlled production of dextrans with varying properties and could be transferred and adapted to other microbes for systematic studies on the release and functionality of native sucrases or other extracellular enzymes.
Head and neck cancer survivors’ preferences for and evaluations of a post-treatment dietary intervention
Authors: Crowder Sylvia L. , Douglas Katherine G. , Frugé Andrew D. , Carroll William R. , Spencer Sharon A. , Locher Julie L. , Demark-Wahnefried Wendy , Rogers Laura Q. , Arthur Anna E.
Published: September 2019

Background

Dietary preferences vary depending on cancer type. The purpose of this study was to report dietary intervention preferences and a study program evaluation from post-treatment head and neck cancer survivors participating in a dietary intervention.

Methods

Between January 2015 and August 2016, 24 head and neck cancer survivors participated in a 12-week randomized clinical dietary intervention trial that promoted weekly consumption of 2.5 cups of cruciferous vegetables and 3.5 cups of green leafy vegetables. At study completion, survivors completed a preferences survey and a study program evaluation to probe interests and improvement aspects for planning future dietary intervention trials. Descriptive statistics (means and frequencies) were generated for multiple choice question responses. Responses to open-ended questions were recorded and grouped based on themes, and verified by quality assurance checks by a second study team member.

Results

Twenty-three survivors completed the preferences and evaluation surveys (response rate 96%). Overall, most participants reported a preference for one-on-one telephone counseling from a registered dietitian nutritionist before beginning treatment. Ninety-six percent of participants ranked the overall study program as “very good” to “excellent,” and all agreed the objectives of the study were clear, the study staff was helpful and easy to contact, and the registered dietitian nutritionist was knowledgeable.

Conclusions

Future research and dietary intervention planning for head and neck cancer survivors should focus on strategies to promote one-on-one telephone or other distance-based counseling combined with face-to-face visits, according to survivor preference.
Fibroblast-derived CXCL12 regulates PTEN expression and is associated with the proliferation and invasion of colon cancer cells via PI3k/Akt signaling
Authors: Ma Jiachi , Sun Xiaowen , Wang Yimin , Chen Bangling , Qian Liyu , Wang Yaguo
Published: September 2019

Background

Stromal-derived CXCL12 play an important role which influence the proliferation and invasiveness of colon cancer in microenvironment. The present study aimed to analyze the underlying mechanism by which CXCL12 and tumour suppressor protein phosphatase and tensin homologue deleted on chromosome 10 (PTEN) influences the metastatic potential of colon cancer and internal relation of colon cancer and stromal cells.

Methods

RT-PCR and western blot were detected the expression of CXCL12, CXCR4 and PTEN in colon cancer cells and stromal cells. The co-operative effects of CXCL12 and PTEN on proliferation and invasion of colon cancer cells were evaluated by real-time PCR, proliferation and invasion assays using an in vitro system consisting of co-cultured cancer cells and stromal cells. We eventually investigated activation of PI3K/Akt signaling by CXCL12 regulate PTEN and involved in the metastatic process of colon cancer. In addition, we also examine how the knockdown of PTEN influences proliferation and invasion and correlate with CXCL12/CXCR4/PI3K/Akt, determination of PTEN up-down-stream targets that preferentially contribute to tumorigenesis.

Results

Blockage of PTEN phosphorylation led to a stronger enhancement of cell proliferation and invasion upon stimulation with CXCL12 via its activation of the PI3K/Akt signaling pathway. Furthermore, knockdown of PTEN by siRNA transfection was also found to enhance the activation of the PI3K/Akt pathway, thereby promoting cell invasion and proliferation. CXCL12 induced transcriptional down-regulation of activated PTEN and this signaling pathway promotes cell survival. CXCL12/CXCR4/PI3K/Akt cascade may be critical for colon cancer cells to metastasize.

Conclusions

Based on our results, we suggest that the modification of CXCR4, PTEN, or PI3K function might be promising new therapeutic approaches to inhibit the aggressive spread of colon cancer.
Childhood mortality, intra-household bargaining power and fertility preferences among women in Ghana
Authors: Novignon Jacob , Djossou Nadege Gbetoton , Enemark Ulrika
Published: September 2019

Background

Continuing population growth could be detrimental for social and economic wellbeing. Understanding the factors that influence family planning decisions will be important for policy. This paper examines the effect of childhood mortality and women’s bargaining power on family planning decisions.

Methods

Data was from the 2014 Ghana Demographic and Health Survey (DHS). A sample of 3313 women in their reproductive age were included in this study. We created variables on women’s exposure to and experience of child mortality risks. Three different indicators of women’s bargaining power in the household were also used. Probit models were estimated in accordance with the nature of the dependent variable.

Results

Results from the probit models suggest that child mortality has a positive association with higher fertility preference. Also, child mortality risks and woman’s bargaining power play important roles in a woman’s fertility choices in Ghana. Women with higher bargaining power were likely to prefer fewer children in the face of child mortality risks, compared to women with lower bargaining power.

Conclusion

In addition to public sensitization campaigns on the dangers of high fertility and use of contraceptives, the findings of this study emphasize the need to focus on reducing child mortality and improving women bargaining power in developing countries.
Differential contractile response of critically ill patients to neuromuscular electrical stimulation
Authors: Grunow Julius J. , Goll Moritz , Carbon Niklas M. , Liebl Max E. , Weber-Carstens Steffen , Wollersheim Tobias
Published: September 2019

Background

Neuromuscular electrical stimulation (NMES) has been investigated as a preventative measure for intensive care unit-acquired weakness. Trial results remain contradictory and therefore inconclusive. As it has been shown that NMES does not necessarily lead to a contractile response, our aim was to characterise the response of critically ill patients to NMES and investigate potential outcome benefits of an adequate contractile response.

Methods

This is a sub-analysis of a randomised controlled trial investigating early muscle activating measures together with protocol-based physiotherapy in patients with a SOFA score ≥ 9 within the first 72 h after admission. Included patients received protocol-based physiotherapy twice daily for 20 min and NMES once daily for 20 min, bilaterally on eight muscle groups. Electrical current was increased up to 70 mA or until a contraction was detected visually or on palpation. Muscle strength was measured by a blinded assessor at the first adequate awakening and ICU discharge.

Results

One thousand eight hundred twenty-four neuromuscular electrical stimulations in 21 patients starting on day 3.0 (2.0/6.0) after ICU admission were included in this sub-analysis. Contractile response decreased from 64.4% on day 1 to 25.0% on day 7 with a significantly lower response rate in the lower extremities and proximal muscle groups. The electrical current required to elicit a contraction did not change over time (day 1, 50.2 [31.3/58.8] mA; day 7, 45.3 [38.0/57.5] mA). The electrical current necessary for a contractile response was higher in the lower extremities. At the first awakening, patients presented with significant weakness (3.2 [2.5/3.8] MRC score). When dividing the cohort into responders and non-responders (> 50% vs. ≤ 50% contractile response), we observed a significantly higher SOFA score in non-responders. The electrical current necessary for a muscle contraction in responders was significantly lower (38.0 [32.8/42.9] vs. 54.7 [51.3/56.0] mA,p < 0.001). Muscle strength showed higher values in the upper extremities of responders at ICU discharge (4.4 [4.1/4.6] vs. 3.3 [2.8/3.8] MRC score,p = 0.036).

Conclusion

Patients show a differential contractile response to NMES, which appears to be dependent on the severity of illness and also relevant for potential outcome benefits.

Trial registration

ISRCTNISRCTN19392591, registered 17 February 2011
Perioperative antibiotic prescribing in surgery departments of two private sector hospitals in Madhya Pradesh, India
Authors: Machowska Anna , Sparrentoft Jonatan , Dhakaita Shyam Kumar , StålsbyLundborg Cecilia , Sharma Megha
Published: September 2019

Background

Single-dose perioperative antibiotic prophylaxis (PAP) is recommended for clean, non-infectious surgeries to prevent surgical site infections. However, the common practice of unindicated use and prolonged use of antibiotics contributes to the development and spread of antibiotic resistance (ABR). The present study explores the perioperative use of antibiotics among inpatients with surgical indications at surgery departments of a teaching (TH) and a non-teaching (NTH) tertiary care hospital in Madhya Pradesh, India.

Methods

Data was collected manually for all inpatients for 3 years (April 2008–August 2011). Patients with non-infectious surgical indications were selected for detailed analysis at the diagnosis group level.

Results

Out of 12,434 enrolled inpatients (TH 6171 and NTH 6263), the majority (> 85%) received antibiotics. None of the inpatients received the recommended single-dose PAP. The average duration of antibiotic treatment was significantly longer at the TH compared to the NTH (9.5 vs 4.4 days, p < 0.001). Based on the study aim, 5984 patients were classified in four diagnosis groups: upper or lower urinary tract surgery indications (UUTSI and LUTSI), and routine or emergency abdominal surgery indications (RASI and EASI). In both hospitals, quinolones were the most prescribed antibiotics for UUTSI (TH 70%, NTH 37%) and LUTSI (TH 70%, NTH 61%) antibiotic. In the TH, aminoglycosides (TH 32%) were commonly prescribed for RASI and imidazole derivatives (75%) for EASI. In the NTH, cephalosporins (39%) and imidazole derivatives (56%) were the most prescribed in RASI and EASI, respectively.

Conclusions and recommendations

High prescribing of antibiotics in all four selected diagnoses groups was observed at both hospitals. In spite of the recommended single-dose PAP, antibiotics were mainly prescribed for longer durations. The unrecommended use of antibiotics is a risk factor for the development of AMR. Improving the quality of antibiotic prescribing by a stewardship program focusing on the development and implementation of local prescribing guidelines is needed.
Extent of predation bias present in migration survival and timing of Atlantic salmon smolt (Salmo salar) as suggested by a novel acoustic tag
Authors: Daniels Jason , Sutton Stephen , Webber Dale , Carr Jonathan
Published: September 2019

Background

Acoustic telemetry is increasingly being used as a tool to measure survival, migration timing and behaviour of fish. Tagged fish may fall prey to other animals with the tag continuing to be detected whilst it remains in the gastrointestinal tract of the predator. Failure to identify post-predation detections introduces “predation bias” into the data. We employed a new predator tag technology in the first known field trial to understand the extent these tags could reduce predation bias in Atlantic salmon (Salmo salar L.) smolt migration through a 65-km zone beginning in freshwater and extending through an estuary. These tags signal predation by detecting a pH change in the predators’ gut during digestion of a tagged prey. We quantified survival and timing bias by comparing measurements from non- and post-predated detections of tagged individuals’ to only those detections where predation was not signalled.

Results

Of the 50 fish tagged, 41 were detected with 24 of these signalling as predated. Predation bias was greatest in the upper estuary and decreased towards the bay. Survival bias peaked at 11.6% at river km 54. Minimum and maximum migration time were both biased long and were 16% and 4% greater than bias corrected timing at river km 66 and 54, respectively. After correcting for bias, the apparent survival from release through freshwater and estuary was 19% and minimum and maximum migration timing was 6.6 and 7.0 days, respectively.

Conclusions

Using this tag, we identified a high proportion of predation events that may have otherwise gone unnoticed using conventional acoustic tags. Estimated survival presented the greatest predation bias in the upper estuary which gradually declined to nearly no apparent bias in the lower estuary as predated tags failed through time to be detected. This is most likely due to tag expulsion from the predator between or upstream of receiver arrays. Whilst we have demonstrated that predation can bias telemetry results, it appears to be rather short-lived given the apparent retention times of these tags within the predators introducing the bias.
Regulatory framework in Pakistan: situation analysis of medicine quality and future recommendations
Authors: Rasheed Huma , Hoellein Ludwig , Bukhari Khalid Saeed , Holzgrabe Ulrike
Published: September 2019

Background

Quality issues in pharmaceuticals are identified as a huge global and public health problem, especially with reference to low- and middle-income countries like Pakistan. The 2011 “Fake Drug Crisis” acted as a driving force to reform the regulatory structures of the country and for establishing the autonomous “Drug Regulatory Authority of Pakistan”. Despite the fact that Pakistan possesses a huge pharmaceutical industry, there is a severe dearth of published literature and scientific evidence for the country regarding medicine quality and the prevalence of counterfeit and low-quality products, respectively.

Aims and objectives

This narrative review covers relevant features of the regulatory framework for pharmaceuticals in Pakistan, its national pharmaceutical industry, as well as a compilation and analysis of published literature for documentation of the country’s situation regarding the overall quality of medicines.

Methods

Available data including scientific publications on the quality of pharmaceuticals in peer reviewed journals, research reports, notifications, and alerts issued by the World Health Organization and other agencies were accessed and compiled. Post graduate dissertations were used to represent unpublished research data and drug safety alerts issued from the local Pakistan authority were analysed to assess the type and number of quality failures reported for pharmaceuticals.

Results

It could be clearly shown that there is negligible scientific data available on the issue of medicine quality in Pakistan. The anticipated number of 40–50% of poor-quality drugs in Pakistan cannot be defended by data available from the literature. Accessible technologies and strategies used in recent years at global level, especially in developing countries, were also reviewed and recommendations are devised for Pakistan to combat the fight against poor-quality medicines.

Conclusion

The case reports, investigations, and general data listed for Pakistan suggest the need of strengthening regulatory systems for premises and GMP inspections, analytical laboratories, as well as an overall capacity building in the field of unravelling and controlling substandard and falsified medicines. It is proposed that well-planned and properly funded studies need to be carried out for collecting critical statistics regarding the prevalence of substandard and falsified medicines in Pakistan.
Similarity assessment of quality attributes of biological medicines: the calculation of operating characteristics to compare different statistical approaches
Authors: Stangler Thomas , Schiestl Martin
Published: September 2019

The comparison of quality attributes is a key element in the evaluation of both biosimilars and manufacturing process changes for biological medicines. Different statistical approaches are proposed to facilitate such evaluations. However, there is no regulatory consensus on a quantitative and scientifically justified definition and an underlying hypothesis of a statistically equivalent quality. The latter is essential to calculate operating characteristics of different approaches. This article proposes a hypothesis for establishing statistically equivalent quality which is concordant with current regulations. It also describes a tool which allows comparisons of different statistical approaches or tests by calculating the operating characteristics for false acceptance and false rejection rates of a claim for statistically equivalent quality. These error rates should be as low as possible to allow a meaningful application of a statistical approach in regulatory decision making. The described tool can be used to compare different statistical approaches for their suitability and may also facilitate the discussion and development of statistical approaches for comparing quality attributes in similarity assessments in general.
A possible role for sarcosine in the management of schizophrenia
Authors: Curtis David
Published: September 2019

Sarcosine, which is freely sold as a dietary supplement, has pharmacological activity to boost functioning of the glutamatergic N-methyl-d-aspartate receptor (NMDAR) and hence it is a biologically rational treatment for schizophrenia. The small number of studies carried out to date provide some evidence for its efficacy and psychiatrists could consider suggesting its use to their patients.
Persistent vs transient alteration of folliculogenesis and estrous cycle after neonatal vs adult exposure to Bisphenol A
Authors: López-Rodríguez David , Franssen Delphine , Sevrin Elena , Gérard Arlette , Balsat Cédric , Blacher Silvia , Noël Agnès , Parent Anne-Simone
Published: September 2019

Exposure to Bisphenol A (BPA), a ubiquitous endocrine disrupting chemical (EDC) is known to produce variable effects on female puberty and ovulation. This variability of effects is possibly due to differences in dose and period of exposure. Little is known about the effects of adult exposure to environmentally relevant doses of this EDC and the differences in effect after neonatal exposure. This study aims at comparing the effects of neonatal versus adult exposure to a very low or a high dose of BPA for two weeks on ovulation and folliculogenesis and exploring the hypothalamic mechanisms involved in such disruption by BPA. One day-old and 90 day-old female rats received daily subcutaneous injections of corn oil (vehicle) or BPA (25 ng/kg/d or 5 mg/kg/d) for 15 days. Neonatal exposure to both BPA doses significantly disrupted the estrous cycle and induced a decrease in primordial follicles. Effects on estrous cyclicity and folliculogenesis persisted into adulthood, consistent with a disruption of organizational mechanisms. During adult exposure, both doses caused a reversible decrease in antral follicles and corpora lutea. A reversible disruption of the estrous cycle associated with a delay and a decrease in the amplitude of the LH surge was also observed. Alterations of the hypothalamic expression of the clock gene Per1 and the novel reproductive peptide Phoenixin indicated a disruption of the hypothalamic control of the preovulatory LH surge by BPA.
Nature and Critique of Modernity in Shen Congwen
Authors: Wang Ban
Published: September 2019

Contemporary environmental crises have their origin in the anthropocentric view of humans as separable from and superior to the natural world. Anthropocentrism also marks the realist author of modern Chinese fiction. Departing from that human-centered view, Shen Congwen's work evinces a biological perspective and affirms an ecological understanding of life in which the writing self must trace its roots to and reciprocate with other organisms and all-encompassing nature. The animistic language of Shen's writing delves into the ecological and bodily foundation of beauty and arts. Shen's notion of the longue durée of biology and evolution debunks the transient zeitgeist of modern transformation and accelerations, propelled by the human domination of nature and alienation of the human body. Shen's portrayal of sexuality reasserts the reciprocity and entwinement of inner nature with outer nature.
Molecular Field Analysis Using Intermediates in Enantio-Determining Steps Can Extract Information for Data-Driven Molecular Design in Asymmetric Catalysis
Authors: Yamaguchi Shigeru , Sodeoka Mikiko
Published: September 2019

We report that a regression technique, molecular field analysis (MFA), is useful to design molecules in asymmetric catalysis. We found that MFA using intermediate structures in an enantio-determining step enabled extraction and visualization of important 3D-structural information for improving enantioselectivity. Based on the visualized structural information, we designed a catalyst and substrate. DFT calculations indicated that enantioselectivities of the reactions using the compounds would improve significantly. We confirmed experimentally that the designed substrate exhibited higher enantioselectivity than those in the training set.
Bizcool: o caso de uma aceleradora de ideias
Authors: Valadares Gustavo Clemente , Lamboglia Galo Andrés Suasnavas , Sugano Joel Yutaka , Silva João Paulo Nascimento da
Published: September 2019

Esse Caso de Ensino visa estimular a discussão e tomada de decisão acerca de Modelo de Negócios, notadamente, mediante o entendimento do modelo da Bizcool, uma aceleradora de startups inovadora, que utiliza a metodologia de compartilhamento do conhecimento para ampliar e acelerar os negócios das empresas clientes. Este estudo se configura como forma de um caso e apresenta os nove blocos do Canvas da empresa e, com isso, propõe o radar de inovação da Bizcool, apresentando o alinhamento dos cursos para desenvolvimento das ideias dos clientes e a criação de laços entre empreendedores.
Factors associated with poor physical performance in older adults of 11 Peruvian high Andean communities
Authors: Urrunaga-Pastor Diego , Runzer-Colmenares Fernando M. , Arones Tania M. , Meza-Cordero Rosario , Taipe-Guizado Silvana , Guralnik Jack M. , Parodi Jose F.
Published: September 2019

Background: Physical performance in the older adult has been extensively studied. However, only a few studies have evaluated physical performance among older adults of high Andean populations and none have studied the factors associated with it. The objective of this study was to evaluate factors associated with poor physical performance by using the Short Physical Performance Battery (SPPB) in older adults living in 11 Peruvian high Andean communities.

Methods: An analytical cross-sectional study was carried out in inhabitants aged 60 or over from 11 high-altitude Andean communities of Peru during 2013-2017. Participants were categorized in two groups according to their SPPB score: poor physical performance (0-6 points) and medium/good physical performance (7-12 points). Additionally, we collected socio-demographic, medical, functional and cognitive assessment information. Poisson regression models were constructed to identify factors associated with poor physical performance. Prevalence ratio (PR) with 95% confidence intervals (95 CI%) are presented.

Results: A total of 407 older adults were studied. The average age was 73.0 ± 6.9 years (range: 60-94 years) and 181 (44.5%) participants had poor physical performance (0-6 points). In the adjusted Poisson regression analysis, the factors associated with poor physical performance were: female gender (PR=1.29; 95%CI: 1.03-1.61), lack of social support (PR=2.10; 95%CI: 1.17-3.76), number of drugs used (PR=1.09; 95%CI: 1.01-1.17), urinary incontinence (PR=1.45; 95%CI: 1.16-1.82), exhaustion (PR=1.35; 95%CI: 1.03-1.75) and cognitive impairment (PR=1.89; 95%CI: 1.40-2.55).

Conclusions: Almost half of the population evaluated had poor physical performance based on the SPPB. Factors that would increase the possibility of suffering from poor physical performance were: female gender, lack of social support, number of drugs used, urinary incontinence, exhaustion and cognitive impairment. Future studies with a larger sample and longitudinal follow-up are needed to design beneficial interventions for the high Andean population.
Optimal price-based control of heterogeneous thermostatically controlled loads under uncertainty using LSTM networks and genetic algorithms
Authors: Nakabi Taha Abdelhalim , Toivanen Pekka
Published: September 2019

In this paper, we consider the problem of thermostatically controlled load (TCL) control through dynamic electricity prices, under partial observability of the environment and uncertainty of the control response. The problem is formulated as a Markov decision process where an agent must find a near-optimal pricing scheme using partial observations of the state and action. We propose a long-short-term memory (LSTM) network to learn the individual behaviors of TCL units. We use the aggregated information to predict the response of the TCL cluster to a pricing policy. We use this prediction model in a genetic algorithm to find the best prices in terms of profit maximization in an energy arbitrage operation. The simulation results show that the proposed method offers a profit equal to 96% of the theoretical optimal solution.