bluuebunny/crossref_metadata_2025 huggingface dataset:
Pharmacist’s role in HIV care in France. Implication for clinical improvement of people living with HIV worldwide
Authors: Jacomet Christine , Langlois Julie , Secher Solene , Coban Dilek , Lambert Celine , Zucman David , Trout Herve , Maarek Rene , Billaud Eric , Certain Agnes
Published: September 2020

In France, antiretroviral (ARV) treatment can be dispensed by hospital and/or community pharmacies. Since January 2016, an online patient medication file can be used to optimize dispensing, but medication interviews have not yet been incorporated into this system. To understand both people living with HIV (PLHIV) and their pharmacists’ habits and expectations of patient medication file and interviews, two consecutive national surveys were organized. The first one, carried out in October 2016 in care centers, was an anonymous questionnaire for PLHIV. The second one was an online survey for community and hospital pharmacies conducted in February 2017. A total of 1137 PLHIV (68% men, of mean age 50.2 ± 11.5 years, CD4 count 671 ± 354, 90% with undetectable HIV viral load (VL) and 64.2% reporting comorbidities) and 246 pharmacies responded. While the existence of the online medication file is known by 58% of PLHIV, only 40% of pharmacists declare it to be systematically offered. It was offered to 120/694 (17%) PLHIV and 96 (80%) accepted it. Currently, 78 (7%) PLHIV feel well taken care of because they are offered medication interviews, 343/1078 (32%) would like to take advantage of this program, mainly those with a shorter ARV duration (OR ARV duration 0.97 [0.95‐0.99]), a VL less often undetectable (OR undetectable VL 0.55 [0.31‐0.98]), and those who feel anxious more often (OR anxious 2.38 [1.48‐3.84]). These results suggest that better implementation of medication files and interviews will strengthen current clinical pathways.
Pharmacological hypothesis: TPC2 antagonist tetrandrine as a potential therapeutic agent for COVID‐19
Authors: Heister Paula M. , Poston Robin N.
Published: September 2020

More than ten million patients worldwide have been diagnosed with coronavirus disease 19 (COVID‐19) to date (WHO situation report, 1st July 2020). There is no vaccine to prevent infection with the causative organism, severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), nor a cure. In the struggle to devise potentially useful therapeutics in record time, the repurposing of existing compounds is a key route of action. In this hypothesis paper, we argue that the bisbenzylisoquinoline and calcium channel blocker tetrandrine, originally extracted from the plant Stephania tetrandra and utilized in traditional Chinese medicine, may have potential in the treatment of COVID‐19 and should be further investigated. We collate and review evidence for tetrandrine's putative mechanism of action in viral infection, specifically its recently discovered antagonism of the two‐pore channel 2 (TPC2). While tetrandrine's particular history of use provides a very limited pharmacological dataset, there is a suggestion from the available evidence that it could be effective at doses used in clinical practice. We suggest that further research to investigate this possibility should be conducted.
GLM profile monitoring using robust estimators
Authors: Moheghi Hamid Reza , Noorossana Rassoul , Ahmadi Orod
Published: September 2020

It is well known that performance of control scheme in phase II of statistical process control depends on the estimators utilized in phase I. Sometimes, outliers may be present in the data, which could seriously impact the performance of the estimators. In some practical situations, generalized linear models (GLMs) are used to model a wide class of response variables. This study deals with the robust estimation and monitoring of parameters in GLM profiles in the presence of outliers. In this study, robust estimators are used to estimate the parameters of logistic and Poisson profiles. The results are compared with the maximum likelihood estimators (MLEs). In a numerical example, the profile parameters are estimated by the MLE and robust estimators and the resulting test statistics are monitored by a control scheme. The phase II control charts are determined based on these two types of estimators and compared for different out‐of‐control conditions. The simulation results confirm that robust estimators in most cases lead to better estimates in comparison with the MLE estimator in terms of average run length criterion.
Iterative learning control for one‐sided Lipschitz nonlinear singular conformable differential equations
Authors: Wang Xiaowen , Wang JinRong
Published: September 2020

This article contributes to a detailed convergence analysis of iterative learning control for singular conformable differential equations with one‐sided Lipschitz nonlinearity. In order to track the desired reference trajectory in a finite time interval, a closed‐loop D‐type learning update law is proposed for such nonlinear systems. Here, the strict convergence analysis is derived under the condition of identical initial state. A numerical example is provided to verify the effectiveness of the proposed controller.
Distributed proximal‐gradient algorithms for nonsmooth convex optimization of second‐order multiagent systems
Authors: Wang Qing , Chen Jie , Zeng Xianlin , Xin Bin
Published: September 2020

This article studies the distributed nonsmooth convex optimization problems for second‐order multiagent systems. The objective function is the summation of local cost functions which are convex but nonsmooth. Each agent only knows its local cost function, local constraint set, and neighbor information. By virtue of proximal operator and Lagrangian methods, novel continuous‐time distributed proximal‐gradient algorithms with derivative feedback are proposed to solve the nonsmooth convex optimization for the consensus and resource allocation of multiagent systems, respectively. With the proposed algorithms, both the consensus and resource allocation problems are solved. Moreover, the system can converge to the optimal solution. Finally, simulation examples are given to illustrate the effectiveness of the proposed algorithms.
Ground‐to‐GEO optical feeder links for very high throughput satellite networks: Accent on diversity techniques
Authors: Mengali Alberto , Kourogiorgas Charilaos I. , Lyras Nikolaos K. , Shankar Mysore Rama Rao Bhavani , Kayhan Farbod , Panagopoulos Athanasios D. , Bäumer Thomas , Liolis Konstantinos
Published: September 2020

This paper studies the use of optical feeder links in very high throughput satellites (VHTS) networks with emphasis on gateway diversity techniques to mitigate the inherent propagation losses in optical frequencies. Focusing on a GEO scenario, the paper considers a system‐wide approach investigating various challenges of optical feeder links. These include transmission schemes amenable for transparent on‐board processing, optical channel models taking into account blockage by clouds and fading caused by atmospheric turbulence in addition to complexity of on‐board and on‐ground processing. The channel models are then used to dimension the ground segment towards ensuring a given availability percentage (e.g., 99.9%). The channel model and payload complexity further influence the choice of link layer techniques used for counteracting fading due to atmospheric turbulence in the absence of blockage. An elaborate end‐to‐end simulator incorporating the proposed channel models capturing the nuances of various processing blocks like optical‐electrical conversion is developed. The system performance results provide interesting insights and a framework for assessing the feasibility and advantages of optical feeder links in VHTS systems.
Sodium Ion Microscale Electrochemical Energy Storage Device: Present Status and Future Perspective
Authors: Ma Jiaxin , Zheng Shuanghao , Das Pratteek , Lu Pengfei , Yu Yan , Wu Zhong-Shuai
Published: September 2020

The unprecedented development of flexible, wearable, and miniaturized electronics has envisaged a glorious future for mankind. However, at the same time, it has escalated the demand for microscale electrochemical energy storage devices (MEESDs). With abundant resources, low cost and properties similar to lithium, sodium ion MEESDs (NIMEESDs), e.g., sodium ion microcapacitors (NIMCs) and microbatteries (NIMBs), have emerged as high‐performance and competitive candidates for effectively powering microelectronics. Herein, the state‐of‐the‐art advances and recent developments in designing high‐performance NIMEESDs are reviewed. The study begins by introducing NIMEESDs, focusing on distinct device configurations, including stacked, interdigital, fiber‐shaped, and 3D geometries. Subsequently, the recent achievements of various well‐designed microelectrodes in Na ion storage covering intercalation, conversion, and alloying‐type reaction mechanisms are systematically discussed. Based on the device architecture, the status of high‐power and high‐energy NIMCs and NIMBs is presented. More attention is paid to the exceptional flexibility, aesthetic versatility, shape diversity, and tailored integration of NIMEESDs. Finally, future challenges associated with NIMEESDs and corresponding prospects are discussed from the viewpoint of electrochemical active materials, electrode structure, microfabrication process, and self‐powered integrated microsystems.
Incorporating Harvesters’ Knowledge into an Index of Abundance for Atlantic Halibut in the Northwest Atlantic
Authors: Hansell Alexander C. , DeCelles Gregory R. , Kersula Michael E. , Cadrin Steven X.
Published: September 2020

Recent stock assessments of Atlantic Halibut Hippoglossus hippoglossus in the United States have been unable to determine stock status. Although there are several fishery‐independent surveys available in the region, few Atlantic Halibut are typically encountered, the survey indices are highly variable, and a reliable index of abundance is not available for this stock. In the absence of reliable fishery‐independent surveys, standardized CPUE time series from the fishery can be used as an index of abundance. Incorporating harvesters’ knowledge into the CPUE standardization process can be beneficial because harvesters are knowledgeable about their fishery and target species and can provide valuable information on factors affecting catch rates and patterns in catch rates. In this study, we interviewed Atlantic Halibut harvesters in Maine to determine which covariates influence catch rates and we incorporated those covariates as predictor variables in the CPUE standardization of logbook data (2002–2017) from Maine’s state Atlantic Halibut fishery. Harvesters identified covariates (fishing location and an interaction of depth and month) that significantly influenced Atlantic Halibut catchability. The standardized time series showed a stable or slightly increasing trend in Atlantic Halibut catch rates, which was consistent with most harvesters’ perspectives. The results from this study highlight the value of collaborative research and provide information for management as a relatively empirical indicator of abundance.
Recent Advances in Synthesis of Chiral Thioethers
Authors: Chen Hongyi , Jiang Wenlong , Zeng Qingle
Published: September 2020

Chiral thioethers is an important class of organosulfur molecules with extensive applications, especially in the field of medicine and organic synthesis. This review discusses the recent progress of synthesis of enantioenriched chiral thioethers and hopes to be helpful for related research in the future. It is summarized from organosulfur compounds‐participating organic reaction types, including nucleophilic substitution, cross coupling, sulfa‐Michael addition, sulfenylation, asymmetric allylic reaction, asymmetric Doyle‐Kirmse reaction, Pummerer‐type rearrangement, Smiles rearrangement,[2,3] Stevens and Sommelet‐Hauser rearrangement.
Gallic acid: A promising genoprotective and hepatoprotective bioactive compound against cyclophosphamide induced toxicity in mice
Authors: Shruthi S , Shenoy K. Bhasker
Published: September 2020

Cyclophosphamide (CP) is a potent chemotherapeutic agent and is also known to interact with specific biological molecules and produce numerous side effects such as genotoxicity, neurotoxicity, reproductive toxicity and nephrotoxicity. CP induces genotoxicity by generating oxygen/nitrogen derived free radicals during chemotherapy and causes DNA damage. Hence, to overcome such side effects of chemotherapeutic agents antioxidants are recommended. Gallic acid (GA) a phenolic compound is commonly exists in variety of fruits and in many plants. In the present study, genoprotecive effects of GA against CP induced genotoxicity in Swiss albino mice were evaluated by using comet assay, bone marrow, and peripheral micronucleus (MN) assays. CP produced oxidative stress induced hepatic damage was assessed by estimating the activity of liver superoxide dismutase (SOD), reduced glutathione content (GSH), and also by examining the histological alterations induced by CP in hepatic tissue of mice. It was noticed that, GA pretreatment significantly reduced the frequency of MN and DNA strand breaks induced by CP. GA also protected the hepatic tissue against CP induced reactive oxygen species (ROS) mediated damage and was evident by increased levels of liver SOD and GSH. GA ameliorated the histological changes induced by CP in hepatic tissue. These findings suggest that, GA is a versatile antioxidant with promising protection against CP induced genotoxicity and hepatic damage in Swiss albino mice.
Sorafenib reduces steatosis‐induced fibrogenesis in a human 3D co‐culture model of non‐alcoholic fatty liver disease
Authors: Romualdo Guilherme Ribeiro , Da Silva Tereza Cristina , de Albuquerque Landi Marina Frota , Morais Juliana Ávila , Barbisan Luis Fernando , Vinken Mathieu , Oliveira Cláudia Pinto , Cogliati Bruno
Published: September 2020

Non‐alcoholic fatty liver disease (NAFLD) affects around 25% of the worldwide population. Non‐alcoholic steatohepatitis (NASH), the more progressive variant of NAFLD, is characterized by steatosis, cellular ballooning, lobular inflammation, and may culminate on hepatic stellate cell (HSC) activation, thus increasing the risk for fibrosis, cirrhosis, and HCC development. Conversely, the antifibrotic effects of sorafenib, an FDA‐approved drug for HCC treatment, have been demonstrated in 2D cell cultures and animal models, but its mechanisms in a NAFLD‐related microenvironment in vitro requires further investigation. Thus, a human 3D co‐culture model of fatty hepatocytes and HSC was established by culturing hepatoma C3A cells, pre‐treated with 1.32 mM oleic acid, with HSC LX‐2 cells. The fatty C3A/LX‐2 spheroids showed morphological and molecular hallmarks of altered lipid metabolism and steatosis‐induced fibrogenesis, similarly to the human disease. Sorafenib (15 μM) for 72 hours reduced fatty spheroid viability, and upregulated the expression of lipid oxidation‐ and hydrolysis‐related genes, CPT1 and LIPC, respectively. Sorafenib also inhibited steatosis‐induced fibrogenesis by downregulating COL1A1, TGFB1, PDGF, and TIMP1 and by decreasing protein levels of IL‐6, TGF‐β1, and TNF‐α in fatty spheroids. The demonstration of the antifibrotic properties of sorafenib on steatosis‐induced fibrogenesis in a 3D in vitro model of NAFLD supports its clinical use as a therapeutic agent for the treatment of NAFLD/NASH patients.
Data analysis onnonstandardspaces
Authors: Huckemann Stephan F. , Eltzner Benjamin
Published: September 2020

The task to write ondata analysis on nonstandard spacesis quite substantial, with a huge body of literature to cover, from parametric to nonparametrics, from shape spaces to Wasserstein spaces. In this survey we convey simple (e.g., Fréchet means) and more complicated ideas (e.g., empirical process theory), common to many approaches with focus on their interaction with one‐another. Indeed, this field is fast growing and it is imperative to develop a mathematical view point, drawing power, and diversity from a higher level of abstraction, for example, by introducing generalized Fréchet means. While many problems have found ingenious solutions (e.g., Procrustes analysis for principal component analysis [PCA] extensions on shape spaces and diffusion on the frame bundle to mimic anisotropic Gaussians), more problems emerge, often more difficult (e.g., topology and geometry influencing limiting rates and defining generic intrinsic PCA extensions). Along this survey, we point out some open problems, that will, as it seems, keep mathematicians, statisticians, computer and data scientists busy for a while.

This article is categorized under:

Statistical and Graphical Methods of Data Analysis > Analysis of High Dimensional Data
Location Data as Contractual Counter-Performance: A Consumer Perspective on Recent EU Legislation
Authors: Efroni Zohar
Published: September 2020

This chapter analyses recent developments in the area of digital consumer law in the EU while focusing on the ‘data as counter-performance’ quandary and its application to location data. The immense technological and economic significance of location data in smart urban spaces renders them a relevant subject for inquiry in the context of ongoing legal efforts to protect consumers who grant permission to use their location data in exchange for digital goods and services.
Supplemental cerclage wiring in angle stable plate fixation of distal tibial spiral fractures enables immediate post-operative full weight-bearing: a biomechanical analysis
Authors: Sandriesser Sabrina , Förch Stefan , Mayr Edgar , Schrödl Falk , von Rüden Christian , Augat Peter
Published: September 2020

Purpose

Distal tibial fractures generally require post-operative weight-bearing restrictions. Especially geriatric patients are unable to follow these recommendations. To increase post-operative implant stability and enable early weight-bearing, augmentation of the primary osteosynthesis by cerclage is desirable. The purpose of this study was to identify the stabilizing effects of a supplemental cable cerclage following plate fixation of distal tibial spiral fractures compared to solitary plate osteosynthesis.

Methods

In eight synthetic tibiae, a reproducible spiral fracture (AO/OTA 42-A1.1c) was stabilized by angle stable plate fixation. Each specimen was statically loaded under combined axial and torsional loads to simulate partial (200 N, 2 Nm) and full (750 N, 7 Nm) weight-bearing. Tests were repeated with supplemental cable cerclage looped around the fracture zone. In a subsequent stepwise increased dynamic load scenario, construct stiffness and interfragmentary movements were analyzed.

Results

With supplemental cable cerclage, construct stiffness almost tripled compared to solitary plate osteosynthesis (2882 ± 739 N/mm vs. 983 ± 355 N/mm;p < 0.001). Under full weight-bearing static loads, a supplemental cerclage revealed reduced axial (− 55%;p = 0.001) and shear movement (− 83%;p < 0.001), and also lowered shear movement (− 42%;p = 0.001) compared to a solitary plate under partial weight-bearing. Under dynamic loads supplemental cerclage significantly reduced axial (p = 0.005) as well as shear movements (p < 0.001).

Conclusion

Supplemental cable cerclage significantly increases fixation stiffness and reduces shear movement in distal tibial spiral fractures. This stabilizing effect enables from a biomechanical point of view immediate mobilization without any weight-bearing restrictions, which may improve the quality of care of orthopedic patients and may trigger a change towards early weight-bearing regimes, especially geriatric patients would benefit from.
Acute-on-chronic subdural hematoma: a new entity for prophylactic anti-epileptic treatment?
Authors: Won Sae-Yeon , Dubinski Daniel , Freiman Thomas , Seifert Volker , Gessler Florian , Strzelczyk Adam , Konczalla Juergen
Published: September 2020

Purpose

Acute-on-chronic subdural hematoma (acSDH) describes acute bleeding into a chronic subdural hematoma (SDH), after surgery or second trauma. Because seizures are a well-known complication of SDH, associated with substantial morbidity and mortality, we aimed to analyze the incidence of acute symptomatic seizures (ASz), including status epilepticus, and determine the functional outcomes in this specific cohort of patients.

Methods

A retrospective analysis was performed, including patients with acSDH who were admitted to our department between 2010 and 2019. The incidence and timely onset of ASz and status epilepticus were evaluated. Functional outcomes at discharge and at 3–6 month follow-up were analyzed based on the modified Rankin scale.

Results

Of 506 patients with chronic SDH, 29 patients (5.7%) were diagnosed with acSDH. The overall incidence of ASz and status epilepticus were 72.4% and 10.3%, respectively. Favorable outcomes were identified in 11 patients (52.4%) in the ASz group compared with 6 patients (75%) in the non-ASz group. The mortality rate was higher in the ASz group compared with that in the control group (29% vs 0%). At follow-up, favorable outcomes were similar to those observed at discharge (52.4% in the ASz group and 71.4% in the control group). The mortality rate was still higher in the ASz group, at 32% compared with 14% for the control group.

Conclusion

AcSDH has a high risk for ASz, including status epilepticus, and is associated with unfavorable outcomes and high mortality. Thus, prophylactic treatment with antiepileptic drugs should be considered among this specific cohort of patients.
Patientenaufkommen, Diagnosen und Verletzungsmechanismen eines überregionalen Traumazentrums mit Beginn der COVID-19-Pandemie im Vergleich zum Mittelwert der 3 Vorjahre
Authors: Graulich T. , Gerhardy J. , Gräff P. , Örgel M. , Omar Pacha T. , Krettek C. , Macke C. , Liodakis E.
Published: September 2020

Hintergrund

Im Rahmen der COVID-19-Pandemie wurden zur Reduktion der Infektionszahlen politische Entscheidungen getroffen, die die soziale Interaktion reduzieren sollen. Ziel hierbei war das Schaffen von Kapazitäten zur innerhospitalen Versorgung der erkrankten Patienten.

Ziel der Arbeit

Ob seit Beginn der getroffenen Maßnahmen auch eine Reduktion des unfallchirurgischen Patientenaufkommens im Vergleich zum Mittelwert der 3 Vorjahre zu beobachten ist, sollte geprüft werden.

Material und Methoden

Es wurden retrospektiv alle Patienten, die sich in unserer unfallchirurgischen Notaufnahme im Zeitraum vom 01.03.2020 bis 15.04.2020 vorgestellt haben, mit dem Mittelwert der Patienten der 3 Vorjahre 2017–2019 verglichen. Es wurden Alter der Patienten, Vorstellungszeitpunkt, Diagnosen, Verbleib der Patienten, stationär oder ambulant, Anzahl und Dauer der operativen Versorgung und benötigte Kapazität auf Normal- und Intensivstation erhoben. Der Verletzungsmechanismus wurde ebenfalls untersucht.

Ergebnisse

Es wurden insgesamt 4967 Patienten im Beobachtungszeitraum vom 01.03.–15.04. eingeschlossen. Im Schnitt der 3 Vorjahre wurden insgesamt 1348 Patienten, d. h. pro Tag 29,3 Patienten vorstellig. Im Jahr 2020 wurden insgesamt 923, d. h. pro Tag 20 Patienten vorstellig (p < 0,01).

Im Schnitt der Vorjahre wurden 227 (24,6 %) im Vergleich zu 2020 311,5 (23,1 %) stationär aufgenommen. Im Schnitt der Vorjahre resultierten 143 im Vergleich zu 2020 mit 136 Operationen hieraus. Die stationären Tage waren von 2442 im Schnitt der Vorjahre, im Jahr 2020, mit 1172 Tagen um 52,1 % reduziert. Die Anzahl der Tage auf der ICU betrug im Mittel der Vorjahre 450 Tage und im Jahr 2020 303 Tage (−32,7 %).

Diskussion

Das Patientenaufkommen in der unfallchirurgischen Notaufnahme war im Beobachtungszeitraum im Jahr 2020 im Vergleich zum Mittelwert der 3 Vorjahre deutlich reduziert. Hierdurch sind direkt Ressourcen für die Betreuung von COVID-19-Patienten frei geworden.
Cryogenic orthogonal turning of Ti-6Al-4V
Authors: Stampfer Benedict , Golda Philipp , Schießl Robert , Maas Ulrich , Schulze Volker
Published: September 2020

Cooling of machining operations by liquid nitrogen is a promising approach for reducing cutting temperatures, increasing tool life and improving the workpiece surface integrity. Unfortunately, the cooling fluid tends to evaporate within the supply channel. This induces process variations and hinders the use of nitrogen cooling in commercial applications. In this work, the coolant is applied via the tool’s rake face during orthogonal turning of Ti-6Al-4V. The effect of a nitrogen supply pressure adjustment and a subcooler usage—proposed here for the first time for machining—is analyzed in terms of process forces, tool temperatures and wear patterns, taken dry cutting as a reference. Thereby, reliable cooling strategies are identified for cryogenic cutting.
Adding a Preoperative Dose of LMWH may Decrease VTE Following Bariatric Surgery
Authors: Abdelsalam Ahmed Mohammed , ElAnsary Ahmed Mohammed Salah Eldeen , Salman Mohammed Abdallah , Nassef Sahar Abdelrahman , Elfergany Hala Mostafa , Aisha Hesham Ahmed Abou
Published: September 2020

Background

Bariatric procedures are the most effective management for obesity. There is no standard venous thromboembolism (VTE) prophylaxis for both dosing and duration of anticoagulation following laparoscopic sleeve gastrectomy. Our purpose was to assess the optimum regimen for VTE prophylaxis in bariatric procedures and to reduce the incidence of perioperative bleeding.

Methods and materials

This is a prospective randomized study which involved 100 morbidly obese patients, subdivided into two groups; group A received postoperative low molecular weight heparin (LMWH) prophylaxis alone starting from day 1 to day 15 in dose 1 mg/kg/day in a maximum dose 120 mg/day, and group B received both pre‐ and postoperative LMWH; at night of surgery 12 h preoperatively and postoperative starting from day 1 to day 15 with the same dose. All patients underwent mesenteric and bilateral lower limbs duplex 15 days postoperative using Philips iU machine and linear (L9‐3), convex (C5‐1) and sector (S5‐1) probes.

Results

Regarding postoperative VTE, we found statistically significant increase in postoperative VTE in patients of group A (four cases) without any case complicated with VTE in patients of group B (P value = 0.041). Regarding postoperative bleeding, we found statistically insignificant percent of cases complicated with postoperative bleeding in group B compared to group A (P value 0.315).

Conclusion

Preoperative as well as a postoperative prophylactic anticoagulant as LMWH is recommended to prevent perioperative VTE. There was an insignificant increase in postoperative bleeding in patients who received preoperative prophylactic anticoagulants.
Modal reconstruction of transverse mode-locked laser beams
Authors: Schepers Florian , Hellwig Tim , Fallnich Carsten
Published: September 2020

Transverse mode-locking in an end-pumped solid state laser by amplitude modulation with an acousto-optic modulator was investigated. Using the stochastic parallel gradient descent algorithm the modal power coefficients and the modal phases of the transverse mode-locked (TML) laser beam were reconstructed from the measured spatial and spatio-temporal intensity distributions, respectively. The distribution of the reconstructed modal power coefficients revealed that the average mode order of the transverse mode-locking process could be increased by a factor of about 8 compared to previous works, corresponding to an increase in the normalized oscillation amplitude by a factor of about 3. Furthermore, we found that besides a non-Poissonian modal power distribution, strong aberrations of the modal phases occurred in the experiment, resulting in a deformation of the oscillating spot. Additionally, we demonstrated the generation of up to four spots oscillating simultaneously on parallel traces by operating the TML laser on a higher mode order in the orthogonal direction to the transverse mode-locking process. TML lasers are of interest, e.g., for beam scanning purposes, as they have the potential to enable spot resolving rates in the multi-GHz regime.
Association between cannabinoid 1 receptor availability and glutamate levels in healthy controls and drug-free patients with first episode psychosis: a multi-modal PET and 1H-MRS study
Authors: Borgan Faith , Veronese Mattia , Reis Marques Tiago , Lythgoe David J. , Howes Oliver
Published: September 2020

Cannabinoid 1 receptor and glutamatergic dysfunction have both been implicated in the pathophysiology of schizophrenia. However, it remains unclear if cannabinoid 1 receptor alterations shown in drug-naïve/free patients with first episode psychosis may be linked to glutamatergic alterations in the illness. We aimed to investigate glutamate levels and cannabinoid 1 receptor levels in the same region in patients with first episode psychosis. Forty volunteers (20 healthy volunteers, 20 drug-naïve/free patients with first episode psychosis diagnosed with schizophrenia/schizoaffective disorder) were included in the study. Glutamate levels were measured using proton magnetic resonance spectroscopy. CB1R availability was indexed using the distribution volume (VT (ml/cm3)) of [11C]MePPEP using arterial blood sampling. There were no significant associations between ACC CB1R levels and ACC glutamate levels in controls (R = − 0.24, p = 0.32) or patients (R = − 0.10, p = 0.25). However, ACC glutamate levels were negatively associated with CB1R availability in the striatum (R = − 0.50, p = 0.02) and hippocampus (R = − 0.50, p = 0.042) in controls, but these associations were not observed in patients (p > 0.05). Our findings extend our previous work in an overlapping sample to show, for the first time as far as we’re aware, that cannabinoid 1 receptor alterations in the anterior cingulate cortex are shown in the absence of glutamatergic dysfunction in the same region, and indicate potential interactions between glutamatergic signalling in the anterior cingulate cortex and the endocannabinoid system in the striatum and hippocampus.
Treatment of rheumatic immune-related adverse events due to cancer immunotherapy with immune checkpoint inhibitors—is it time for a paradigm shift?
Authors: Chatzidionysiou Katerina , Liapi Matina , Tsakonas Georgios , Gunnarsson Iva , Catrina Anca
Published: September 2020

Immunotherapy has revolutionized cancer treatment during the last years. Several monoclonal antibodies that are specific for regulatory checkpoint molecules, that is, immune checkpoint inhibitors (ICIs), have been approved and are currently in use for various types of cancer in different lines of treatment. Cancer immunotherapy aims for enhancing the immune response against cancer cells. Despite their high efficacy, ICIs are associated to a new spectrum of adverse events of autoimmune origin, often referred to as immune-related adverse events (irAEs), which limit the utility of these drugs. These irAEs are quite common and can affect almost every organ. The grade of toxicity varies from very mild to life-threatening. The pathophysiological mechanisms behind these events are not fully understood. In this review, we will summarize current evidence specifically regarding the rheumatic irAEs and we will focus on current and future treatment strategies. Treatment guidelines largely support the use of glucocorticoids as first-line therapy, when symptomatic therapy is not efficient, and for more persistent and/or moderate/severe degree of inflammation. Targeted therapies are higher up in the treatment pyramid, after inadequate response to glucocorticoids and conventional, broad immunosuppressive agents, and for severe forms of irAEs. However, preclinical data provide evidence that raise concerns regarding the potential risk of impaired antitumoral effect. This potential risk of glucocorticoids, together with the high efficacy and potential synergistic effect of newer, targeted immunomodulation, such as tumor necrosis factor and interleukin-6 blockade, could support a paradigm shift, where more targeted treatments are considered earlier in the treatment sequence.
Higher education and sustainable development goal 16 in fragile and conflict-affected contexts
Authors: Milton Sansom
Published: September 2020

Sustainable Development Goal 16 commits to ‘promote peaceful and inclusive societies for sustainable development, provide access to justice for all and build effective, accountable and inclusive institutions at all levels’. While the concerns of SDG16 with violence reduction, rule of law, and governance are relevant to all societies, this paper focuses on fragile and conflict-affected countries, many of which have the hardest task in achieving SDG16. It analyses how higher education can contribute towards—or detract from—SDG16 through teaching, research, governance, and external leadership. It then analyses four dynamics influencing the agency of universities in fragile and conflict-affected contexts in engaging with SDG16: resource mobilisation and the public good; securitisation; academic freedom, insecurity, and politicisation; and tensions between demands for localisation and the universalising logics of liberal peacebuilding models and the SDGs.
The inter-relationship between no harm, equitable and reasonable utilisation and cooperation under international water law
Authors: Tanzi Attila M.
Published: September 2020

The chapter addresses the no-harm principle as a core pillar of the international water law regime, and its inter-relationship with the principles of equitable and reasonable utilisation and cooperation. No harm will be described in its harmonised relation to the latter two principles under the “community interest” approach to transboundary watercourses, as enunciated by the Permanent Court of International Justice and later corroborated by the International Court of Justice. Such a harmonised construction of the three-pronged body of international water law will be illustrated as one disproving any alleged priority or, conversely, subservience of either principle with respect to the others. It will also be shown how the same construction emphasises the integration and inter-relationship between the legal principles at hand.
Habitat suitability and connectivity modeling reveal priority areas for Indiana bat (Myotis sodalis) conservation in a complex habitat mosaic
Authors: Cable Ashleigh B. , O’Keefe Joy M. , Deppe Jill L. , Hohoff Tara C. , Taylor Steven J. , Davis Mark A.
Published: September 2020

Context

Conservation for the Indiana bat (Myotis sodalis), a federally endangered species in the United States of America, is typically focused on local maternity sites; however, the species is a regional migrant, interacting with the environment at multiple spatial scales. Hierarchical levels of management may be necessary, but we have limited knowledge of landscape-level ecology, distribution, and connectivity of suitable areas in complex landscapes.

Objectives

We sought to (1) identify factors influencingM. sodalismaternity colony distribution in a mosaic landscape, (2) map suitable maternity habitat, and (3) quantify connectivity importance of patches to direct conservation action.

Methods

Using 3 decades of occurrence data, we testeda priori, hypothesis-driven habitat suitability models. We mapped suitable areas and quantified connectivity importance of habitat patches with probabilistic habitat availability metrics.

Results

Factors improving landscape-scale suitability included limited agriculture, more forest cover, forest edge, proximity to medium-sized water bodies, lower elevations, and limited urban development. Areas closer to hibernacula and rivers were suitable. Binary maps showed that 30% of the study area was suitable forM. sodalisand 29% was important for connectivity. Most suitable patches were important for intra-patch connectivity and far fewer contributed to inter-patch connectivity.

Conclusions

While simple models may be effective for small, homogenous landscapes, complex models are needed to explain habitat suitability in large, mixed landscapes. Suitability modeling identified factors that made sites attractive as maternity areas. Connectivity analysis improved our understanding of important areas for bats and prioritized areas to target for restoration.
The incentives account of feasibility
Authors: Stemplowska Zofia
Published: September 2020

In Utopophobia Estlund offers a prominent version of a conditional account of feasibility. I think the account is too permissive. I defend an alternative incentives account of feasibility (of action). The incentives account preserves the spirit of the conditional account but qualifies fewer actions as feasible. Simplified, the account holds that an action is feasible if there is an incentive such that, given the incentive, the agent is likely to perform the action successfully. If we accept that ought implies feasible, then we should reject some normative requirements on agents that Estlund would accept in light of his more permissive conditional account. But we can still recognise normative requirements on individual and collective agents that, if complied with, would result in a world that is radically better than our own.
Value of the surgeon’s sightline on hologram registration and targeting in mixed reality
Authors: Luzon Javier A. , Stimec Bojan V. , Bakka Arne O. , Edwin Bjørn , Ignjatovic Dejan
Published: September 2020

Purpose

Mixed reality (MR) is being evaluated as a visual tool for surgical navigation. Current literature presents unclear results on intraoperative accuracy using the Microsoft HoloLens 1®. This study aims to assess the impact of the surgeon’s sightline in an inside-out marker-based MR navigation system for open surgery.

Methods

Surgeons at Akershus University Hospital tested this system. A custom-made phantom was used, containing 18 wire target crosses within its inner walls. A CT scan was obtained in order to segment all wire targets into a single 3D-model (hologram). An in-house software application (CTrue), developed for the Microsoft HoloLens 1, uploaded 3D-models and automatically registered the 3D-model with the phantom. Based on the surgeon’s sightline while registering and targeting (free sightline /F/or a strictly perpendicular sightline /P/), 4 scenarios were developed (FF-PF-FP-PP). Target error distance (TED) was obtained in three different working axes-(XYZ).

Results

Six surgeons (5 males, age 29–62) were enrolled. A total of 864 measurements were collected in 4 scenarios, twice. Scenario PP showed the smallest TED in XYZ-axes mean = 2.98 mm ± SD 1.33; 2.28 mm ± SD 1.45; 2.78 mm ± SD 1.91, respectively. Scenario FF showed the largest TED in XYZ-axes with mean = 10.03 mm ± SD 3.19; 6.36 mm ± SD 3.36; 16.11 mm ± SD 8.91, respectively. Multiple comparison tests, grouped in scenarios and axes, showed that the majority of scenario comparisons had significantly different TED values (p < 0.05). Y-axis always presented the smallest TED regardless of scenario tested.

Conclusion

A strictly perpendicular working sightline in relation to the 3D-model achieves the best accuracy results. Shortcomings in this technology, as an intraoperative visual cue, can be overcome by sightline correction. Incidentally, this is the preferred working angle for open surgery.
FRAX: re-adjust or re-think
Authors: El Miedany Yasser
Published: September 2020

Since its development in 2008, FRAX has booked its place in the standard day to day management of osteoporosis. The FRAX tool has been appreciated for its simplicity and applicability for use in primary care, but criticised for the same reason, as it does not take into account exposure response. To address some of these limitations, relatively simple arithmetic procedures have been proposed to be applied to the conventional FRAX estimates of hip and major fracture probabilities aiming at adjustment of the probability assessment. However, as the list of these adjustments got longer, this has reflected on its implementation in the standard practice and gave FRAX a patchy look. Consequently, raises the need to re-think of the current FRAX and whether a second generation of the tool is required to address the perceived limitations of the original FRAX. This article will discuss both point of views of re-adjustment and re-thinking.
Experimental trauma rapidly modifies functional connectivity
Authors: Gvozdanovic Geraldine , Seifritz Erich , Stämpfli Philipp , Canna Antonietta , Rasch Björn , Esposito Fabrizio
Published: September 2020

Traumatic events can produce emotional, cognitive and autonomous physical responses. This may ultimately lead to post-traumatic stress disorder (PTSD), a psychiatric syndrome which requires comprehensive treatment. Trauma exposure alters functional connectivity; however, onset and nature of these changes are unknown. Here, we explore functional connectivity changes at rest directly after experimental trauma exposure. Seventy-three healthy subjects watched either a trauma or a control film. Resting state functional magnetic resonance imaging measurements were conducted before and directly after the film. Seed-based analyses revealed trauma-related changes in functional connectivity, specifically including decreases of connectivity between amygdala and middle temporal gyrus and increases between hippocampus and precuneus. These central effects were accompanied by trauma-related increases in heart rate. Moreover, connectivity between the amygdala and middle temporal gyrus predicted subsequent trauma-related valence. Our results demonstrate rapid functional connectivity changes in memory-related brain regions at rest after experimental trauma, selectively relating to changes in emotions evoked by the trauma manipulation. Results could represent an early predictive biomarker for the development of trauma-related PTSD and thus provide an indication for the need of early targeted preventive interventions.
Pegvisomant in combination or pegvisomant alone after failure of somatostatin analogs in acromegaly patients: an observational French ACROSTUDY cohort study
Authors: Kuhn Emmanuelle , Caron Philippe , Delemer Brigitte , Raingeard Isabelle , Lefebvre Hervé , Raverot Gérald , Cortet-Rudelli Christine , Desailloud Rachel , Geffroy Clementine , Henocque Robin , Brault Yves , Brue Thierry , Chanson Philippe
Published: September 2020

Objective

After surgery, when somatostatin analogs (SAs) do not normalise IGF-I, pegvisomant (PEG) is indicated. Our aim was to define the medical reasons for the treatment of patients with PEG as monotherapy (M) or combined with SA, either as primary bitherapy, PB (PEG is secondarily introduced after SA) or as secondary bitherapy, SB (SAs secondarily introduced after PEG).

Methods

We retrospectively analysed French data from ACROSTUDY.

Results

167, 88 and 57 patients were treated with M, PB or SB, respectively, during a median time of 80, 42 and 70 months. The median PEG dose was respectively 15, 10 and 20 mg. Before PEG, the mean IGF-I level did not differ between M and PB but the proportion of patients with suprasellar tumour extension was higher in PB group (67.5% vs. 44.4%, P = 0.022). SB regimen was used preferentially in patients with tumour increase and IGF-I level difficult to normalise under PEG. In both secondary regimens, the decrease of the frequency of PEG’s injections, compared to monotherapy was confirmed. However, the mean weekly dose of PEG between M and PB remained the same.

Conclusions

The medical rationale for continuing SAs rather than switching to PEG alone in patients who do not normalise IGF-I under SAs was a tumour concern with suprasellar extension and tumour shrinkage under SA. A potential explanation for introducing SA in association with PEG appears to be a tumour enlargement and difficulties to normalise IGF-I levels under PEG given alone. In both regimens, the prospect of lowering PEG injection frequency favoured the choice.
Narrative Devices: Neurotechnologies, Information, and Self-Constitution
Authors: Postan Emily
Published: September 2020

This article provides a conceptual and normative framework through which we may understand the potentially ethically significant roles that information generated by neurotechnologies about our brains and minds may play in our construction of our identities. Neuroethics debates currently focus disproportionately on the ways that third parties may (ab)use these kinds of information. These debates occlude interests we may have in whether and how we ourselves encounter information about our own brains and minds. This gap is not yet adequately addressed by most allusions in the literature to potential identity impacts. These lack the requisite conceptual or normative foundations to explain why we should be concerned about such effects or how they might be addressed. This article seeks to fill this gap by presenting a normative account of identity as constituted by embodied self-narratives. It proposes that information generated by neurotechnologies can play significant content-supplying and interpretive roles in our construction of our self-narratives. It argues, to the extent that these roles support and detract from the coherence and inhabitability of these narratives, access to information about our brains and minds engages non-trivial identity-related interests. These claims are illustrated using examples drawn from empirical literature reporting reactions to information generated by implantable predictive BCIs and psychiatric neuroimaging. The article concludes by highlighting ways in which information generated by neurotechnologies might be governed so as to protect information subjects’ interests in developing and inhabiting their own identities.
Sozialraumorientierte Schulsozialarbeit an Sekundarschulen in Baden-Württemberg
Authors: Zipperle Mirjana , Maier Katharina , Gschwind Andreas Karl
Published: September 2020

Das Forschungsprojekt „Sozialraumorientierte Schulsozialarbeit an Sekundarschulen in Baden-Württemberg“ (SOSSA_SEK) untersucht im Auftrag des Kommunalverbands für Jugend und Soziales Baden-Württemberg Praxen, Rahmenbedingungen und Nutzen sozialraumorientierter Schulsozialarbeit an Sekundarschulen. Mit Hilfe eines multiperspektivischen Forschungsdesigns wird das professionelle Handeln von Schulsozialarbeitsfachkräften und deren Bezüge zu den Sozialräumen der Jugendlichen analysiert. Ausgangspunkt des Projekts ist die Annahme, dass eine (sozial-)räumliche Orientierung von Schulsozialarbeitsfachkräften auf das unmittelbare Umfeld der Schule nicht ausreicht, um die Aneignungsräume von Jugendlichen zu erfassen und als Teil lebensweltorientierter Arbeit in die sozialarbeiterische Praxis zu integrieren. Das Projekt zielt auf Erkenntnisse zu den Möglichkeiten und Bedingungen einer über die Schule hinausreichenden Schulsozialarbeit und deren Bezüge zu außerschulischen Akteuren entsprechend den Sozialräumen der Jugendlichen.