bluuebunny/crossref_metadata_2025 huggingface dataset:
Optimization of machining parameters when machining beyond recommended cutting speed
Authors: Kaladhar M.
Published: August 2020

Purpose

Even though austenitic stainless steels have been extensively used in industries, owing to some of the characteristics of the material, its performance in machining is difficult to understand, in particular at high cutting speeds. There is no availability of dependable and in-depth studies pertinent to this matter. In this work, performance of AISI 304 austenitic stainless steel was studied in terms of surface roughness (Ra) and material removal rate (MRR) at high cutting speeds. Subsequently, parametric optimization and prediction for responses were carried out.

Design/methodology/approach

Turning operations were conducted using L9 orthogonal array and the outcomes were analyzed to attain optimal set of machining parameters for the responses using signal-to-noise (S/N) ratio and Pareto analysis of variance (ANOVA). In the present work, the cutting speed values were considered beyond the recommended range as designated by tool manufacturers. Finally, multiple regression models were developed to predict responses.

Findings

From the results, 350 m/min was found to be a significant speed. The investigation reveals that even though the speeds are taken beyond the recommended values, the results are favorable. The optimal machining parameters values for surface quality obtained were cutting speed of 350 m/min, feed of 0.15 mm/rev and depth of cut of 2.0 mm. In case of MRR, the optimal values were: cutting speed of 400 m/min, feed of 0.25 mm/rev and depth of cut of 2.0 mm. It was found out that there was an improvement in Ra and MRR (around 15 and 4%) due to optimization. The results indicate that Pareto ANOVA is easier than S/N ratio. This revealed that the feed rate and depth of cut were mostly affected parameters for Ra and MRR. The developed models are capable of predicting the responses accurately.

Practical implications

The outcome of the work reveals that even though the speeds were taken beyond the recommended value, the results are favorable for manufacturing industries when the tool cost is considered insignificant.

Originality/value

No work was reported on machining of the chosen material beyond the recommended cutting speed. Moreover, it was observed from the past works that cutting speeds were limited to 100–300 m/min.
Maladaptive migration behaviour in hybrids links to predator‐mediated ecological selection
Authors: Pärssinen Varpu , Hulthén Kaj , Brönmark Christer , Skov Christian , Brodersen Jakob , Baktoft Henrik , Chapman Ben B. , Hansson Lars‐Anders , Nilsson Per Anders
Published: August 2020

Different migratory species have evolved distinct migratory characteristics that improve fitness in their particular ecological niches. However, when such species hybridize, migratory traits from parental species can combine maladaptively and cause hybrids to fall between parental fitness peaks, with potential consequences for hybrid viability and species integrity.

Here, we take advantage of a natural cross‐breeding incident to study migratory behaviour in naturally occurring hybrids as well as in their parental species and explore links between migratory traits and predation risk.

To achieve this, we used electronic tags and passive telemetry to record detailed individual migration patterns (timing and number of migratory trips) in two common freshwater fish species, roach Rutilus rutilus, common bream Abramis brama as well as their hybrids. Next, we scanned for tags regurgitated by a key avian predator (great cormorant Phalacrocorax carbo) at nearby roosting sites, allowing us to directly link migratory behaviour to predation risk in the wild.

We found that hybrid individuals showed a higher number of short, multi‐trip movements between lake and stream habitats as compared to both parental species. The mean date of first lake departure differed between bream and roach by more than 10 days, while hybrids departed in two distinct peaks that overlapped with the parental species' averages. Moreover, the probability of cormorant predation increased with multi‐trip movement frequency across species and was higher for hybrids.

Our data provide novel insights into hybrid viability, with links to predator‐mediated ecological selection. Increased exposure to predators via maladaptive migratory behaviour reduces hybrid survival and can thereby reinforce species integrity.
Effects of spatial distances on the assemblage dissimilarity of macroinvertebrates with different dispersal pathways and abilities in southern Brazilian streams
Authors: Kotzian Carla Bender , Pires Mateus Marques , Hepp Luiz Ubiratan
Published: August 2020

The magnitude of distance–decay relationships (DDRs) in stream macroinvertebrates can vary with their preferential dispersal pathways (overland and watercourse) and abilities as well as with environmental dissimilarity. We assessed DDRs in the compositional dissimilarity of macroinvertebrate assemblages in southern Brazilian streams using overland and watercourse distances (WD) as explanatory variables. We conducted additional separate assessments for taxonomic groups and according to a classification that took into account differences in the dispersal abilities and main pathways among macroinvertebrates. Assessments were conducted separately for (a) strong‐flying insects with overland dispersal (Anisoptera), (b) weak‐flying insects dispersing preferably through riparian corridors (Chironomidae, Ephemeroptera, Plecoptera, Trichoptera and Zygoptera), and (c) watercourse dispersers (Mollusca, Psephenidae and Elmidae). The environmental dissimilarity associated with spatial extent was accounted for via partial Mantel tests. Overland and WD were positively correlated with the dissimilarity of the total macroinvertebrate assemblage, weak‐flying insects, watercourse dispersers, and most taxonomic groups. DDRs were stronger with overland than WD. However, no consistent pattern emerged after accounting for environmental dissimilarity. Strong‐ and weak‐flying insects were correlated with environment, while watercourse dispersers, with geographic distances. Additionally, taxonomic groups were differently related with environment and geographic distances. The distinct responses of each taxonomic group to the environmental specificities of the study area such as substrate composition and land use likely explain the observed results. Thus, our findings indicate that combining taxonomic and natural history information is an effective approach for comprehending the underlying mechanisms generating spatial structure in stream macroinvertebrate assemblages.
Species interaction: Revisiting its terminology and concept
Authors: Nakazawa Takefumi
Published: August 2020

Terminology can profoundly influence scientific research. Here, I discuss the term “species interaction,” which constitutes the core of ecology. The term has the merits of underlying many fundamental ecological ideas (e.g., competitive exclusion, trophic cascade and keystone predation) and making ecological research more interdisciplinary (e.g., biodiversity conservation and ecosystem management). Meanwhile, it has the demerits of causing problems of synonymy and polysemy, masking the fact that interactions occur at the individual level, and reinforcing the counterfactual view that an ecological community is a network of interactions between homogeneous species. This means that the facile use of the term may impede our understanding of community dynamics, which is a great concern considering recent evidence that individual heterogeneity is ubiquitous (e.g., due to ontogeny, sex and genotype) and crucial for community dynamics. To further extend the debate, I present some prospective scenarios in which future research trends may affect the importance of the terminological debate. For example, the term may obtain other definitions due to the establishment of new analytical techniques (e.g., DNA metabarcoding and causation analysis), or the debate may become obsolete if a consensus is reached that interactions occur between individuals (i.e., a paradigm shift). These arguments indicate that how we can use the term depends on how we view interactions between organisms. I suggest that multifaceted approaches that consider not only the terminology but also its associated concept and relevant research methodology are needed to overcome the issues of such ambiguous terminology and guide the future development of ecology.
Resistance to serine in Bacillus subtilis: identification of the serine transporter YbeC and of a metabolic network that links serine and threonine metabolism
Authors: Klewing Anika , Koo Byoung‐Mo , Krüger Larissa , Poehlein Anja , Reuß Daniel , Daniel Rolf , Gross Carol A. , Stülke Jörg
Published: August 2020

The Gram‐positive bacterium Bacillus subtilis uses serine not only as a building block for proteins but also as an important precursor in many anabolic reactions. Moreover, a lack of serine results in the initiation of biofilm formation. However, excess serine inhibits the growth of B. subtilis. To unravel the underlying mechanisms, we isolated suppressor mutants that can tolerate toxic serine concentrations by three targeted and non‐targeted genome‐wide screens. All screens as well as genetic complementation in Escherichia coli identified the so far uncharacterized permease YbeC as the major serine transporter of B. subtilis. In addition to YbeC, the threonine transporters BcaP and YbxG make minor contributions to serine uptake. A strain lacking these three transporters was able to tolerate 100 mM serine whereas the wild type strain was already inhibited by 1 mM of the amino acid. The screen for serine‐resistant mutants also identified mutations that result in increased serine degradation and in increased expression of threonine biosynthetic enzymes suggesting that serine toxicity results from interference with threonine biosynthesis.
Ricardo flies Ryanair: Strategic human resource management and competitive advantage in a Single European Aviation Market
Authors: Harvey Geraint , Turnbull Peter
Published: August 2020

How and why are some firms, such as Ryanair, able to consistently record industry‐leading profitability that sustains a competitive advantage over their rivals? Human resource management (HRM) plays a critical role in four widely recognised profit‐generating mechanisms, albeit not always in ways predicted by mainstream strategic HRM. Studies of HRM → performance grounded in the resource‐based view of the firm invariably focus on the human resources already controlled by the firm—specifically, resources that are rare, inimitable, non‐substitutable and can be exploited through organisation—rather than strategic factor markets where firms acquire their human resources. In doing so, these studies overlook the industrial relations and wider institutional context that might variously promote, permit or preclude particular HR policies and practices. It is only when different profit‐generating mechanisms, either in isolation or combination, are activated under the auspicious conditions of a particular time and place that HRM contributes to sustained competitive advantage.
A chromosome‐scale reference genome and genome‐wide genetic variations elucidate adaptation in yak
Authors: Ji Qiu‐mei , Xin Jin‐wei , Chai Zhi‐xin , Zhang Cheng‐fu , Dawa Yangla , Luo Sang , Zhang Qiang , Pingcuo Zhandui , Peng Min‐Sheng , Zhu Yong , Cao Han‐wen , Wang Hui , Han Jian‐lin , Zhong Jin‐cheng
Published: August 2020

Yak is an important livestock animal for the people indigenous to the harsh, oxygen‐limited Qinghai‐Tibetan Plateau and Hindu Kush ranges of the Himalayas. The yak genome was sequenced in 2012, but its assembly was fragmented because of the inherent limitations of the Illumina sequencing technology used to analyse it. An accurate and complete reference genome is essential for the study of genetic variations in this species. Long‐read sequences are more complete than their short‐read counterparts and have been successfully applied towards high‐quality genome assembly for various species. In this study, we present a high‐quality chromosome‐scale yak genome assembly (BosGru_PB_v1.0) constructed with long‐read sequencing and chromatin interaction technologies. Compared to an existing yak genome assembly (BosGru_v2.0), BosGru_PB_v1.0 shows substantially improved chromosome sequence continuity, reduced repetitive structure ambiguity, and gene model completeness. To characterize genetic variation in yak, we generated de novo genome assemblies based on Illumina short reads for seven recognized domestic yak breeds in Tibet and Sichuan and one wild yak from Hoh Xil. We compared these eight assemblies to the BosGru_PB_v1.0 genome, obtained a comprehensive map of yak genetic diversity at the whole‐genome level, and identified several protein‐coding genes absent from the BosGru_PB_v1.0 assembly. Despite the genetic bottleneck experienced by wild yak, their diversity was nonetheless higher than that of domestic yak. Here, we identified breed‐specific sequences and genes by whole‐genome alignment, which may facilitate yak breed identification.
Role of YES1 amplification in EGFR mutation‐positive non‐small cell lung cancer: Primary resistance to afatinib in a patient
Authors: Tao Junyan , Sun Dantong , Hou Helei
Published: August 2020

Epidermal growth factor receptor (EGFR) mutation‐positive non‐small cell lung cancer (NSCLC) patients benefit from EGFR tyrosine kinase inhibitors (TKIs), while some patients demonstrate a resistance to EGFR‐TKIs. In the case reported here, the NSCLC patient harboring an EGFR‐sensitive mutation and YES1 amplification was treated with afatinib as first‐line therapy, but was found to have progressive disease four weeks later. During subsequent chemotherapy, this patient's disease progressed rapidly. Mechanisms of primary resistance to EGFR‐TKIs remain unclear. This case suggested that YES1 amplification might be associated with primary resistance to EGFR‐TKIs and YES1 amplification might be a negative predictor of EGFR‐TKI treatment in NSCLC patients harboring EGFR sensitive mutations.
Mitochondrial DNA mutation exacerbates female reproductive aging via impairment of the NADH/NAD+ redox
Authors: Yang Liang , Lin Xiaobing , Tang Haite , Fan Yuting , Zeng Sheng , Jia Lei , Li Yukun , Shi Yanan , He Shujing , Wang Hao , Hu Zhijuan , Gong Xiao , Liang Xiaoyan , Yang Yi , Liu Xingguo
Published: August 2020

Mammals' aging is correlated with the accumulation of somatic heteroplasmic mitochondrial DNA (mtDNA) mutations. Whether and how aging accumulated mtDNA mutations modulate fertility remains unknown. Here, we analyzed oocyte quality of young (≤30 years old) and elder (≥38 years old) female patients and show the elder group had lower blastocyst formation rate and more mtDNA point mutations in oocytes. To test the causal role of mtDNA point mutations on infertility, we used polymerase gamma (POLG) mutator mice. We show that mtDNA mutation levels inversely correlate with fertility, interestingly mainly affecting not male but female fertility. mtDNA mutations decrease female mice's fertility by reducing ovarian primordial and mature follicles. Mechanistically, accumulation of mtDNA mutations decreases fertility by impairing oocyte's NADH/NAD+ redox state, which could be rescued by nicotinamide mononucleotide treatment. For the first time, we answer the fundamental question of the causal effect of age‐accumulated mtDNA mutations on fertility and its sex dependence, and show its distinct metabolic controlling mechanism.
Conservation translocations of Hawaiian monk seals: accounting for variability in body condition improves evaluation of translocation efficacy
Authors: Baker J. D. , Barbieri M. M. , Johanos T. C. , Littnan C. L. , Bohlander J. L. , Kaufman A. C. , Harting A. L. , Farry S. C. , Yoshinaga C. H.
Published: August 2020

To assess the efficacy of conservation translocations, survival of released individuals is typically compared to that of control groups. Such comparisons assume that treatment groups consist of otherwise equivalent individuals. When that assumption is unmet, incorporating physiological parameters may improve assessment of translocation programs. During 2012–2014, 19 weaned female Hawaiian monk seal pups were translocated to sites where survival prospects were expected to be more favorable than at their natal locations. We compared survival from weaning to age two years of translocated pups to two control groups; pups remaining at source sites and pups native to destination sites. To account for the known relationship between weaning girth and survival, we generated probability distributions of the number of survivors at source and destination sites given the weaning girths of translocated seals. Data were available to calculate girth‐adjusted survival probabilities for 13 of the translocated pups. Of these, we estimated that only one pup would have been expected to have survived had the translocated pups remained at their natal site. Seven of the 13 translocated seals survived, a value just below the median (eight) expected to have survived at the destination site. Thus, translocation substantially improved survival. Had we not accounted for weaning girth effects on survival, we would have erroneously concluded that the translocation program had yielded no survival benefit. Identifying and integrating correlates of survival into quantitative analyses associated with conservation translocations can reduce bias and lead to greater success.
Sex‐dependent pharmacological profiles of the synthetic cannabinoid MMB‐Fubinaca
Authors: Oliveira da Cruz José F. , Ioannidou Christina , Pagano Zottola Antonio C. , Muguruza Carolina , Gomez‐Sotres Paula , Fernandez Monica , Callado Luis F. , Marsicano Giovanni , Busquets‐Garcia Arnau
Published: August 2020

Synthetic cannabinoids have emerged as novel psychoactive substances with damaging consequences for public health. They exhibit high affinity at the cannabinoid type‐1 (CB1) receptor and produce similar and often more potent effects as other CB1 receptor agonists. However, we are still far from a complete pharmacological understanding of these compounds. In this study, by using behavioral, molecular, pharmacological, and electrophysiological approaches, we aimed at characterizing several in vitro and in vivo pharmacological effects of the synthetic cannabinoid MMB‐Fubinaca (also known as AMB‐Fubinaca or FUB‐AMB), a particular synthetic cannabinoid. MMB‐Fubinaca stimulates CB1 receptor‐mediated functional coupling to G‐proteins in mouse and human brain preparations in a similar manner as the CB1 receptor agonist WIN55,512‐2 but with a much greater potency. Both drugs similarly activate the CB1 receptor‐dependent extracellular signal‐regulated kinase (ERK) pathway. Notably, in vivo administration of MMB‐Fubinaca in mice induced greater behavioral and electrophysiological effects in male than in female mice in a CB1 receptor‐dependent manner. Overall, these data provide a solid pharmacological profiling of the effects of MMB‐Fubinaca and important information about the mechanisms of action underlying its harmful impact in humans. At the same time, they reinforce the significant sexual dimorphism of cannabinoid actions, which will have to be taken into account in future animal and clinical studies.
A cross‐sectional study exploring obesity and pregnancy planning among women attending an antenatal clinic in Suva, Fiji
Authors: Mudaliar Jyotishna , Nusair Pushpa , McCudden Lucy , Melville Peter , Rouse Ian , Black Kirsten
Published: August 2020

Background

Pregnancy planning enables maternal health optimisation which is particularly important for women who have obesity and are at increased risk of adverse perinatal outcomes.

Aims

The prevalence of pregnancy planning and its relationship to body mass index (BMI) was investigated in a cohort of women attending antenatal clinics in the main referral hospital in Suva, Fiji.

Materials and Methods

The questionnaire captured health and socio‐demographic data, anthropometry and asked about pregnancy planning.

Results

Two thousand, two hundred and three pregnant women presenting for their first booking at the antenatal clinic were enrolled; 721 (37.4%) out of 1926 women with complete data reported they did not plan their pregnancy. A third of women (n = 633, 32.8%) had overweight and 805 (41.7%) had obesity. In multivariable analyses parity, employment status, marital status, and BMI were significantly associated with pregnancy planning. Compared to women of a healthy weight or underweight, women who have obesity were less likely to plan their pregnancy (adjusted odds ratio 0.742; 95% CI 0.569–0.967).

Conclusion

Tackling the cycle of obesity will require attention to preconception care and optimising weight before pregnancy.
Why goal pursuers prefer to seek support from close friends: The roles of concerns for accessibility
Authors: Hui Chin Ming , Fung Jane Mang Yan , Hui Yiu Yuen , Ng Jacky C. K.
Published: August 2020

When selecting among potential supporters, goal pursuers prefer close over distant friends. Using the transactive goal dynamics perspective, we proposed that such preference is partially motivated by concerns for accessibility. Indeed, one correlational study (Study 1) showed that goal pursuers selected close friends partly because they were more accessible. Three additional experiments asked participants to seek support by calling either a close or a distant friend. In this setup, the close friend’s support was either as helpful as (Study 2) or less helpful than the distant friend’s (Studies 3a and 3b). In these situations, we still observed a general preference for close friends, but this preference was reduced (a) when the difficulty of reaching the close friend was elevated (Study 2) and (b) when they could resort to the nonchosen friend if necessary (Studies 3a and 3b). How concerns for accessibility influence the use of social networks will be discussed..
The zebrafish histamine H3 receptor modulates aggression, neural activity and forebrain functional connectivity
Authors: Reichmann Florian , Rimmer Neal , Tilley Ceinwen A. , Dalla Vecchia Elisa , Pinion Joseph , Al Oustah Amir , Carreño Gutiérrez Hector , Young Andrew M. J. , McDearmid Jonathan R. , Winter Matthew J. , Norton William H. J.
Published: August 2020

Aim

Aggression is a behavioural trait characterized by the intention to harm others for offensive or defensive purposes. Neurotransmitters such as serotonin and dopamine are important mediators of aggression. However, the physiological role of the histaminergic system during this behaviour is currently unclear. Here, we aimed to better understand histaminergic signalling during aggression by characterizing the involvement of the histamine H3 receptor (Hrh3).

Methods

We have generated a novel zebrafish Hrh3 null mutant line using CRISPR‐Cas9 genome engineering and investigated behavioural changes and alterations to neural activity using whole brain Ca2+ imaging in zebrafish larvae and ribosomal protein S6 (rpS6) immunohistochemistry in adults.

Results

We show that genetic inactivation of the histamine H3 receptor (Hrh3) reduces aggression in zebrafish, an effect that can be reproduced by pharmacological inhibition. In addition, hrh3−/− zebrafish show behavioural impairments consistent with heightened anxiety. Larval in vivo whole brain Ca2+ imaging reveals higher neuronal activity in the forebrain of mutants, but lower activity in specific hindbrain areas and changes in measures of functional connectivity between subregions. Adult hrh3−/− zebrafish display brain region‐specific neural activity changes in response to aggression of both key regions of the social decision‐making network, and the areas containing histaminergic neurons in the zebrafish brain.

Conclusion

These results highlight the importance of zebrafish Hrh3 signalling for aggression and anxiety and uncover the brain areas involved. Targeting this receptor might be a potential novel therapeutic route for human conditions characterized by heightened aggression.
A phase 2B randomised trial of hyperbaric oxygen therapy for ulcerative colitis patients hospitalised for moderate to severe flares
Authors: Dulai Parambir S. , Raffals Laura E. , Hudesman David , Chiorean Michael , Cross Raymond , Ahmed Tasneem , Winter Michael , Chang Shannon , Fudman David , Sadler Charlotte , Chiu Ernest L. , Ross Frank L. , Toups Gary , Murad M. Hassan , Sethuraman Kinjal , Holm James R. , Guilliod Renie , Levine Benjamin , Buckey Jay C. , Siegel Corey A.
Published: August 2020

Background

Hyperbaric oxygen has been reported to improve disease activity in hospitalised ulcerative colitis (UC) patients.

Aim

To evaluate dosing strategies with hyperbaric oxygen for hospitalised UC patients.

Methods

We enrolled UC patients hospitalised for acute flares (Mayo score 6‐12). Initially, all patients received 3 days of hyperbaric oxygen at 2.4 atmospheres (90 minutes with two air breaks) in addition to intravenous steroids. Day 3 responders (reduction of partial Mayo score ≥ 2 points and rectal bleeding score ≥ 1 point) were randomised to receive a total of 5 days vs 3 days of hyperbaric oxygen.

Results

We treated 20 patients with hyperbaric oxygen (75% prior biologic failure). Day 3 response was achieved in 55% (n = 11/20), with significant reductions in stool frequency, rectal bleeding and CRP (P < 0.01). A more significant reduction in disease activity was observed with 5 days vs 3 days of hyperbaric oxygen (P = 0.03). Infliximab or colectomy was required in only three patients (15%) despite a predicted probability of 80% for second‐line therapy. Day 3 hyperbaric oxygen responders were less likely to require re‐hospitalisation or colectomy by 3 months vs non‐responders (0% vs 66%, P = 0.002). No treatment‐related adverse events were observed.

Conclusion

Hyperbaric oxygen appears to be effective for optimising response to intravenous steroids in UC patients hospitalised for acute flares, with low rates of re‐hospitalisation or colectomy at 3 months. An optimal clinical response is achieved with 5 days of hyperbaric oxygen. Larger phase 3 trials are needed to confirm efficacy and obtain labelled approval.
SnakeMap: four years of experience with a national small animal snake envenomation registry
Authors: Boller M , Kelers K , Stevenson MA , Winkel KD , Hardjo S , Heller J , Judge PR , Ong HM , Padula AM , Reddrop C , Santos LCP , Sharp CR , Smart L , Swindells KL , Tabrett D , Wierenga JR
Published: August 2020

SnakeMap is a national cloud‐based, veterinary snakebite registry. It was designed to prospectively collect data of the clinical circumstances and temporospatial information on cases of snake envenomation in dogs and cats. We herein introduce the project and summarise the data from the first 4 years of SnakeMap. The registry is a veterinary community‐based online database allowing case entry from veterinary hospitals across Australia. Registry data comprise hospital characteristics, patient characteristics, envenoming snake type, treatment and outcome variables, including time and geolocation of the snake bite. We present summative information on select key variables from the SnakeMap registry (1 July 2015 to 30 June 2019). Twenty‐eight hospitals from 6 states/territories entered 624 cases into the registry, including 419 dogs (67%) and 205 cats (33%). Bite time was available in 216 animals of which 90 (42%) were reported to be bitten in the 3 hours between 03:00 pm and 05:59 pm; median bite to presentation interval was 60 (interquartile range [IQR] 30, 211) minutes in dogs and 95 (IQR 41, 238) minutes in cats. Bites occurred in the owner's yard in 356 dogs (85%) and 53 cats (26%). A snake venom detection kit was used in 172 cases (28%) and antivenom was administered in 523 cases (85%). Most animals (n = 534, 88%) survived to discharge (median hospitalisation of 25 [IQR 16, 62] hours). SnakeMap effectively collects relevant clinical data from dogs and cats with presumed snake bite and provides locally specific information on the epidemiology of snake envenomation in small animals.
Androgen derivatives improve blood counts and elongate telomere length in adult cryptic dyskeratosis congenita
Authors: Kirschner Martin , Vieri Margherita , Kricheldorf Kim , Ferreira Monica S. Ventura , Wlodarski Marcin W. , Schwarz Michaela , Balabanov Stefan , Rolles Benjamin , Isfort Susanne , Koschmieder Steffen , Höchsmann Britta , Panse Jens , Brümmendorf Tim H. , Beier Fabian
Published: August 2020

Dyskeratosis Congenita (DKC) is a systemic disorder caused by mutations resulting in impaired telomere maintenance. Clinical features include bone marrow failure and an increased risk of developing hematological malignancies. There are conflicting data whether androgen derivatives (AD) can elongate telomeres in vivo and whether AD treatment enhances the risk of gaining myelodysplastic syndrome‐related mutations. Seven TERC or TERT‐mutated DKC patients underwent AD treatment. All patients revealed hematological response. Telomere length of lymphocytes and granulocytes increased significantly and no MDS‐related mutations were detected. Pending longer follow‐up, treatment with AD seems to represent an efficient and safe therapy for DKC patients.
30,000 Minimum Wages: The Economic Effects of Collective Bargaining Extensions
Authors: Martins Pedro S.
Published: August 2020

Many governments extend the coverage of collective agreements to workers and employers that were not involved in their bargaining. These extensions may address co‐ordination issues but may also distort competition by imposing sector‐specific minimum wages and other work conditions that are not suitable for some firms and workers. In this article, we analyse the impact of such extensions along several economic margins. Drawing on the worker‐ and firm‐level monthly data for Portugal, a country where extensions have been widespread, and the scattered timing of the extensions, we find that, while continuing workers experience wage increases following an extension, formal employment in the relevant sectors falls, on average, by 2 per cent. These results increase by about 25 per cent across small firms and are driven by reduced hirings. In contrast, the employment and wage bills of independent contractors, who are not subject to labour law or collective bargaining, increase by over 1 per cent following an extension.
The role of the gravity forces on firms’ trade
Authors: Navas Antonio , Serti Francesco , Tomasi Chiara
Published: August 2020

Abstract.

This paper offers both a theoretical framework and empirical evidence on the role that the two gravity forces, namely market size and geographical distance, have indirectly through imports, on firms’ exports patterns. The model shows that sourcing from bigger and closer markets implies higher productivity gains that, in turn, increase firms’ ability to enter export market as well as their export value. Exploiting data on product‐ and destination‐level transactions of a large panel of Italian firms, the paper shows that, on average, the indirect effects of the gravity forces are about one third of their direct effects.

Résumé.

Rôle des forces de gravité sur le commerce des entreprises. Cet article offre à la fois un cadre théorique et des preuves empiriques sur le rôle que deux forces de gravité, à savoir la taille du marché et l’éloignement géographique, peuvent indirectement exercer sur les profils d’exportation des entreprise en fonction de leurs importations. Ce modèle montre que l’approvisionnement sur des marchés plus vastes et plus proches engendre de meilleurs gains de productivité, augmentant ainsi la capacité des entreprises à intégrer le marché d’exportation ainsi que la valeur de leurs exportations. En s’appuyant sur des données provenant d’un large panel d’entreprises italiennes et relatives aux transactions par type de produit et par destination, cet article montre qu’en moyenne, les effets indirects des forces de gravité représentent environ un tiers de leurs effets directs.
Novel peptidomimetic peptide deformylase (PDF) inhibitors of Mycobacterium tuberculosis
Authors: Gokhale Kunal M. , Telvekar Vikas N.
Published: August 2020

Emergence of MDR‐TB and XDR‐TB led to the failure of available anti‐tubercular drugs. In order to explore, identify and develop new anti‐tubercular drugs, novel peptidomimetic series of Mtb–peptide deformylase (PDF) inhibitors was designed and synthesized. In vitro antimycobacterial potential of compounds was established by screening of compounds against Mycobacterium tuberculosis H37Rv strain using MABA. Among them, ester series of compounds 4a, 4b, 4c, 4d, and 4e were found most active, with compound 4c being highly active and exhibiting minimum inhibitory concentration of 6.25 µg/ml against M. tb H37Rv strain. Additionally, the compounds were docked to determine the probable binding interactions and understand the mechanism of action of most active molecules on Mtb‐peptide deformylase (PDF), which is involved in the mycobacterium protein synthesis.
The new T3b category has clinical significance? SEER‐based study
Authors: Xiang Jingzhe , Wang Zhihong , Sun Wei , Zhang Hao
Published: August 2020

Objective

As per the eighth edition of the American Joint Committee on Cancer (AJCC) staging system for differentiated thyroid carcinoma (DTC), minimal extrathyroidal extension (mETE) has been removed. Instead, gross ETE (gETE) invading only strap muscles has been designated as a new T3b category. Our objective was to investigate the impact of the T3b category on survival in order to establish its prognostic value in DTC.

Design

In this retrospective study, we included patients who had undergone thyroidectomy between 2004 and 2012. Data from the Surveillance, Epidemiology and End Results (SEER) database were examined.

Methods

We used the Kaplan‐Meier method and log‐rank test to analyse overall survival (OS) and cancer‐specific survival (CSS). The effect of potential predictors associated with survival were estimated using the Cox regression model. To minimize selection bias, propensity‐score matching (PSM) was performed.

Results

A total of 63 315 patients were included in our study. During the average follow‐up duration of nearly 78 months, significant differences were observed in cancer‐specific survival among patients with no ETE, mETE, gETE invading only strap muscles (T3b) and gETE invading perithyroidal structures other than strap muscles (T4) (P < .05). In univariable and multivariate analysis, both mETE and T3b exhibited significant poorer CSS compared with no ETE. After adjusting for patient features with PSM, it was confirmed that T3b was associated with worse CSS compared with no ETE and mETE.

Conclusions

Both mETE and gETE are independent factors for DTC, implying that the new T3b category is worthy of reference for medical workers. Furthermore, mETE was significantly associated with poorer outcome. Our conclusion may provide support for the modification of the TNM staging system in the future.
Caregiver depression and child behaviour problems: A longitudinal mixed effects approach
Authors: Marçal Katherine
Published: August 2020

Caregiver mental health has a powerful influence on child well‐being. Both maternal depression and paternal depression predict behaviour problems in young children. However, little is known about the nature of this link over time. The present study leveraged a large sample of at‐risk families to examine the impact of maternal and paternal depression on trajectories of child behaviour from age 3 to 15. Data came from the At‐Home substudy of the Fragile Families and Child Well‐Being Study, which observed a cohort of children born 1998–2000 in 20 large American cities (N = 1,090). Multiple imputation by chained equations addressed missing data to maximize available information without biasing models. Linear mixed effects models tested the association between caregiver depression and child behaviour over 12 years; interaction models tested whether this association changed as children transitioned into adolescence. Results showed caregiver depression is related with increases in both child internalizing and externalizing problems, and these relationships strengthened over time. Findings inform risk trajectories of distinct behavioural problems, shedding light on the development of child psychopathology and highlighting opportunities for intervention.
Pulmonary embolism in obesity‐hypoventilation syndrome
Authors: Ekici Aydanur , Ekici Mehmet , İleri Şule , Çimen Asiye Büşra , Aslan Habibe
Published: August 2020

Introduction

Obesity‐hypoventilation syndrome occurs with alveolar hypoventilation during sleeping and daytime. Obesity may be a risk factor for venous thromboembolism. However, the venous thromboembolism in the obesity‐hypoventilation syndrome is not well characterized.

Objective

This case series aimed to investigate the presence and clinical features of venous thromboembolism in patients with the obesity‐hypoventilation syndrome.

Methods

Data of eight case reports were collected. Ages ranged from 36 to 73 years.

Results

All patients had mosaic perfusion and enlarged main pulmonary artery, two had signs of infarction and mostly segmental and subsegmental filling defects. On the basis of this information some conclusions can be drawn carefully.

Conclusion

Present cases indicate that pulmonary embolism are also very common in patients with obesity‐hypoventilation syndrome, anticoagulant therapy is at least as important as the treatment of the current disease. Clinicians will frequently be faced with patients with obesity‐hypoventilation syndrome suspected of PE.
The role of infrared dermal thermometry in the management of neuropathic diabetic foot ulcers
Authors: Ghosh A. , Ray S. , Garg M. K. , Chowdhury S. , Mukhopadhyay S.
Published: August 2020

Aim

This prospective observational study evaluated the role of infrared (IR) dermal thermometry in the management of diabetic foot ulcers.

Methods

Thirty participants with unilateral neuropathic diabetic foot ulcers of University of Texas grade 1 or 2 (stage A) were followed up monthly for 1 year. At each visit, skin temperatures were measured with an IR dermal thermometer at corresponding sites on both feet, using the contralateral feet without ulcers as controls.

Results

Average temperature and ulcer temperature in affected feet were significantly higher than in unaffected feet, with a mean difference of 1.2 °C [95% confidence interval (CI) 0.7 to 1.7] and 3.1 °C (95% CI 2.3 to 3.9), respectively. Although the gradient between average temperature of affected foot and that of unaffected foot normalized (mean difference 0.2 °C, 95% CI −0.2 to 0.7) at healing, the temperature gradient between the ulcer and a corresponding site on the unaffected foot decreased but did not normalize (mean difference 2.1 °C, 95% CI 1.2 to 3.1) even at healing, as documented by skin closure, and persisted for up to 1 month after skin closure. A gradient of ≥1 °C between average temperature of affected foot and that of unaffected foot at initial presentation or at any time during ulcer healing was found to predict impaired healing and should alert clinicians to ulcers requiring more attention. An incremental trend in temperature gradient (median difference 2.2 °C; range 0.1–6.3 °C) at a site on the foot was predictive of a recurrent ulcer involving the same site.

Conclusions

IR dermal thermometry may have a role in predicting diabetic foot ulcer healing, in determining the completeness of healing and in guiding the duration of offloading. Serial monitoring of the temperature gradient may predict the development of recurrent diabetic foot ulcers.
Pharmacokinetics, pharmacodynamics and tolerability of single and multiple doses of janagliflozin, a sodium‐glucose co‐transporter‐2 inhibitor, in Chinese people with type 2 diabetes mellitus
Authors: Li Xiaojiao , Zhu Xiaoxue , Liu Jingrui , Li Qianqian , Zhang Hong , Li Cuiyun , Wu Min , Gao Lei , Wen He , Li Xixi , Tang Xinran , Liu Li , Ding Yanhua
Published: August 2020

Aims

To evaluate the pharmacokinetic (PK) and pharmacodynamic (PD) characteristics, and tolerability of janagliflozin, a novel sodium‐glucose co‐transporter‐2 inhibitor, in Chinese people with type 2 diabetes mellitus (T2DM).

Materials and methods

In this study, 36 people with T2DM were randomly assigned in a 1:1:1:1 ratio to receive janagliflozin 25 mg, janagliflozin 50 mg, dapagliflozin 10 mg or placebo. Participants received a single dose on day 1, and were treated once daily from day 4 to day 17.

Results

Following oral administration, janagliflozin was rapidly absorbed, reaching Cmax at 2 hours. The mean half‐life (t1/2) at steady state was approximately 21 to 23 hours. There was no significant accumulation with multiple doses (accumulation factor < 2). In participants treated with janagliflozin 25 mg, janagliflozin 50 mg, dapagliflozin 10 mg or placebo, change in mean 24‐hour urinary glucose excretion from baseline was 92.35, 94.17, 87.61 and 6.26 g after multiple doses, and change in mean fasting plasma glucose level from baseline to day 17 was −2.18, −2.66, −2.79 and 1.70%, respectively. Most adverse events (AEs) were mild or moderate with no deaths, serious AEs, or discontinuations due to AEs.

Conclusions

Single and multiple oral administration (14 days) of janagliflozin 25 mg and 50 mg exhibited favourable PK, PD and tolerability profiles in Chinese people with T2DM, which were comparable to those of dapagliflozin 10 mg. Janagliflozin 25 mg and 50 mg are recommended for further clinical investigation.
Effects of glucagon‐like peptide‐1 receptor agonists liraglutide and semaglutide on cardiovascular and renal outcomes across body mass index categories in type 2 diabetes: Results of the LEADER and SUSTAIN 6 trials
Authors: Verma Subodh , McGuire Darren K. , Bain Stephen C. , Bhatt Deepak L. , Leiter Lawrence A. , Mazer C. David , Monk Fries Tea , Pratley Richard E. , Rasmussen Søren , Vrazic Hrvoje , Zinman Bernard , Buse John B.
Published: August 2020

Associations between body mass index (BMI) and the cardiovascular (CV) and kidney efficacy of glucagon‐like peptide‐1 receptor agonists (GLP‐1 RAs) in patients with type 2 diabetes (T2D) are uncertain; therefore, data analysed separately from the Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results (LEADER) trial and the Trial to Evaluate Cardiovascular and Other Long‐term Outcomes with Semaglutide in Subjects with Type 2 Diabetes (SUSTAIN 6) were examined. These international, randomized, placebo‐controlled trials investigated liraglutide and semaglutide (both subcutaneous) in patients with T2D and at high risk of CV events. In post hoc analyses, patients were categorized by baseline BMI (<25, ≥25‐<30, ≥30‐<35 and ≥35 kg/m2), and CV and kidney outcomes with GLP‐1 RA versus placebo were analysed. All baseline BMI data from LEADER (n = 9331) and SUSTAIN 6 (n = 3290) were included (91% and 92% of patients with overweight or obesity, respectively). In SUSTAIN 6, nominally significant heterogeneity of semaglutide efficacy by baseline BMI was observed for CV death/myocardial infarction/stroke (major adverse CV events, primary outcome of both; Pinteraction = .02); otherwise, there was no statistical heterogeneity for either GLP‐1 RA versus placebo across BMI categories for key CV and kidney outcomes. The lack of statistical heterogeneity from these cardiorenal outcomes implies that liraglutide and semaglutide may be beneficial for many patients and is probable not to depend on their baseline BMI, but further study is needed.
Assessing the cost‐effectiveness of sodium–glucose cotransporter‐2 inhibitors in type 2 diabetes mellitus: A comprehensive economic evaluation using clinical trial and real‐world evidence
Authors: McEwan Phil , Bennett Hayley , Khunti Kamlesh , Wilding John , Edmonds Christopher , Thuresson Marcus , Wittbrodt Eric , Fenici Peter , Kosiborod Mikhail
Published: August 2020

Aims

The economic burden of diabetes is driven by the management of vascular complications. Sodium–glucose cotransporter‐2 inhibitors (SGLT2i) have demonstrated reductions in cardiovascular and renal complications, including hospitalization for heart failure (HHF) and renal disease progression, in randomized clinical trials. The objective of this study was to evaluate the cost‐effectiveness of the SGLT2i class versus standard of care in type 2 diabetes mellitus (T2DM), using evidence from both clinical trial and real‐world studies.

Methods

An established T2DM model was adapted to use contemporary outcomes evidence from real‐world studies and randomized controlled trial evaluations of SGLT2i, and extrapolated over a lifetime for HHF, myocardial infarction, stroke, end‐stage renal disease and all‐cause mortality. The economic analysis considered adults with T2DM, with and without established cardiovascular disease, and was conducted over a lifetime from the perspective of the health care payer in the United Kingdom, United States and China, discounted at country‐specific rates.

Results

SGLT2i were consistently associated with increased treatment costs, reduced complication costs and gains in quality‐adjusted life years driven by differences in projected life expectancy, cardiovascular and microvascular morbidity and weight loss. SGLT2i were estimated to be cost‐saving or cost‐effective at relevant thresholds for the overall population in the United Kingdom, United States and China, with cost‐effectiveness being the greatest in higher risk subgroups.

Conclusions

The findings highlight the need to take into account cost savings from reducing common, morbid and preventable T2DM complications when considering the cost of diabetes medications.
Atlantic salmon living on the edge: Smolt behaviour and survival during seaward migration in River Minho
Authors: Flávio Hugo , Caballero Pablo , Jepsen Niels , Aarestrup Kim
Published: August 2020

The Atlantic salmon (Salmo salar) population of the River Minho represents the southern natural distribution edge of the species. In line with the general trend for Atlantic salmon, this population has been declining over the years and is now at a critically low level. With river connectivity compromised by a large dam just 80 km upstream the River Minho's outlet, and an expected deterioration of climatic conditions, it is urgent to increase our knowledge of this population and identify survival bottlenecks that can be addressed. In this study, we used radio and acoustic telemetry to track Atlantic salmon smolts during their migration towards the sea and record both survival rates and possible causes of mortality. The recorded survival for the tagged migrating Atlantic salmon remained below 55% in the three studied years, indicating that the in‐river loss of smolts is likely a strong constraint to this population. From the smolts to which a likely cause of mortality could be attributed (34%), most appear to have been removed from the river (25%), with two confirmed events of bird predation and one of mammal predation. Interestingly, eight tags were recorded moving back upstream, likely indicating predation by larger fish. Increasing predator populations (e.g. cormorants, Phalacrocorax carbo) and invasive predators (e.g. American mink, Neovison vison) lead to elevated predation pressure on this already strained Atlantic salmon population, and further studies quantifying their impact in more detail could prove crucial for future management considerations.