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More than just a generational shift, the arrival of 5G creates a whole new range of opportunities for every sector of the economy. It signifies a significant change in the function that mobile technology serves in society. As 5G becomes a reality, it will have a huge impact on us, particularly at work. This paper's goal is to conduct a thorough literature review, investigate how intelligent automation might be enabled or streamlined by 5G, and discuss why 5G development and deployment are critical in the future years. This article emphasizes the significance of 5G revolutionary networks, evaluates its essential enabling technologies, looks at its trends and issues with adaptation, looks at its applications in various industries, including Industry 4.0 and digital marketing, and emphasizes its function.

© 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 licenseBackground: Traumatic brain injury (TBI) is increasingly recognised as being responsible for a substantial proportion of the global burden of disease. Neurosurgical interventions are an important aspect of care for patients with TBI, but there is little epidemiological data available on this patient population. We aimed to characterise differences in casemix, management, and mortality of patients receiving emergency neurosurgery for TBI across different levels of human development. Methods: We did a prospective observational cohort study of consecutive patients with TBI undergoing emergency neurosurgery, in a convenience sample of hospitals identified by open invitation, through international and regional scientific societies and meetings, individual contacts, and social media. Patients receiving emergency neurosurgery for TBI in each hospital's 30-day study period were all eligible for inclusion, with the exception of patients undergoing insertion of an intracranial pressure monitor only, ventriculostomy placement only, or a procedure for drainage of a chronic subdural haematoma. The primary outcome was mortality at 14 days postoperatively (or last point of observation if the patient was discharged before this time point). Countries were stratified according to their Human Development Index (HDI)—a composite of life expectancy, education, and income measures—into very high HDI, high HDI, medium HDI, and low HDI tiers. Mixed effects logistic regression was used to examine the effect of HDI on mortality while accounting for and quantifying between-hospital and between-country variation. Findings: Our study included 1635 records from 159 hospitals in 57 countries, collected between Nov 1, 2018, and Jan 31, 2020. 328 (20%) records were from countries in the very high HDI tier, 539 (33%) from countries in the high HDI tier, 614 (38%) from countries in the medium HDI tier, and 154 (9%) from countries in the low HDI tier. The median age was 35 years (IQR 24–51), with the oldest patients in the very high HDI tier (median 54 years, IQR 34–69) and the youngest in the low HDI tier (median 28 years, IQR 20–38). The most common procedures were elevation of a depressed skull fracture in the low HDI tier (69 [45%]), evacuation of a supratentorial extradural haematoma in the medium HDI tier (189 [31%]) and high HDI tier (173 [32%]), and evacuation of a supratentorial acute subdural haematoma in the very high HDI tier (155 [47%]). Median time from injury to surgery was 13 h (IQR 6–32). Overall mortality was 18% (299 of 1635). After adjustment for casemix, the odds of mortality were greater in the medium HDI tier (odds ratio [OR] 2·84, 95% CI 1·55–5·2) and high HDI tier (2·26, 1·23–4·15), but not the low HDI tier (1·66, 0·61–4·46), relative to the very high HDI tier. There was significant between-hospital variation in mortality (median OR 2·04, 95% CI 1·17–2·49). Interpretation: Patients receiving emergency neurosurgery for TBI differed considerably in their admission characteristics and management across human development settings. Level of human development was associated with mortality. Substantial opportunities to improve care globally were identified, including reducing delays to surgery. Between-hospital variation in mortality suggests changes at an institutional level could influence outcome and comparative effectiveness research could identify best practices. Funding: National Institute for Health Research Global Health Research Group.

Entrepreneurial and established firms form collaborative relationships to commercialize products. Through such ties, entrepreneurs seek (1) development help to hone ideas into marketable products a...

Mobile Adhoc NETworks (MANETs) usually present challenges such as a highly dynamic topology due to node mobility, route rediscovery process, and packet loss. This leads to low throughput, a lot of energy consumption, delay and low packet delivery ratio. In order to ensure that the route is not rediscovered over and over, multipath routing protocols such as Adhoc Multipath Distance Vector (AOMDV) is used in order to utilize the alternate routes. However, nodes that have low residual energy can die and add to the problem of disconnection of network and route rediscovery. This paper proposes a multipath routing algorithm based on AOMDV and genetic mutation. It takes into account residual energy, hop count, congestion and received signal strength for primary route selection. For secondary path selection it uses residual energy, hop count, congestion and received signal strength together with mutation. The simulation results show that the proposed algorithm gives better performance results compared to AOMDV by 11% for residual energy, 45% throughput, 3% packet delivery ratio, and 63% less delay.

This article examines how women construct their gameplay identities in relation to the hegemonic “gamer” discourse. The article is based on semi-structured in-depth interviews with women who occupy central roles in the Finnish gaming industry. We deploy Judith Butler’s theorization of performative identity construction to examine how the women negotiate their identity in relation to the hegemonic gamer discourse, focusing on how they both embrace and resist the hegemonic, masculine constructions of gameplay. The study shows the dynamics surrounding the gamer identity. While women submit to the hegemonic gamer discourse, reproducing the masculine gamer notions to gain recognition as a viable member of the gameplay community, the study also identifies how subversive opportunities arise as the women deploy new, alternative versions of gamer identity. The hegemonic discourse is subverted through the identity position of tech-savvy, which departs from the masculine connotations.

How a firm views its competitors affects its performance. We extend the networks literature to examine how a firm’s positioning in competition networks—networks of perceived competitive relations between firms—relates to a significant organizational outcome, namely, product innovation. We find that when firms position themselves in ways that allow them to see differently than rivals, new product ideas emerge. Simply put, firms with an unusual view of competition are more innovative. We situate our analysis in the U.S. enterprise infrastructure software industry, examining the relationship between the firm’s position in competition networks and its innovation over the period of 1995–2012. Using both archival and in-depth field data, we find that two factors—the focal firm’s spanning of structural holes in the network and the perception of peripheral firms as competitors—are positively associated with its product innovation. At the same time, turnover in firms perceived as competitors has an unexpected negative association with innovation. Overall, the findings suggest that firms benefit when they see the competitive landscape differently than their competitors. The findings also show that what we know about innovation-enhancing positioning in collaboration networks does not necessarily hold in competition networks.

Interpersonal touch is crucial for establishing interpersonal bonds. Drawing on the framework of haptic sociality, this study explores the interactional emergence of embodied relationships among second-grade schoolboys as part of ongoing classroom activity. Focussing on forms of body-to-body behaviour that occur during classroom activities, we describe four different types of touch occurring between the boys – supporting, nudging, wrestling and grooming – and how they are collaboratively accomplished, how they change from one type to another, and how they are deployed as embodied negotiation withing a continuously unfolding embodied relationship. Complementing previous studies on embodied relationships among schoolgirls, our study focuses on the haptic social life of schoolboys.

This review essay assesses two new books which will be of particular interest to human rights and peacebuilding practitioners working in post-conflict settings: Ann Petrila and Hasan Hasanović’s Voices from Srebrenica: Survivor Narratives of the Bosnian Genocide and Healing and Peacebuilding after War: Transforming Trauma in Bosnia and Herzegovina, edited by Julianne Funk, Nancy Good, and Marie E. Berry.

This article examines Raoul Peck’s portrayal of post-genocide justice in Rwanda in his film Sometimes in April (2005). The film, which depicts the 1994 genocide against the Tutsi and its aftermath a decade later, resonates with the ICTR case Prosecutor v. Nahimana et al. with its focus on hate speech as genocide. The shared questions connect the two distinct narrative forms that are part of the global social discourse on Rwanda, allowing them to be analysed side by side. Building upon close readings, this article asks: Who is guilty and what counts as a crime? What kind of impact do justice mechanisms have? Whose interests does the ICTR serve? Extending interdisciplinary research on Rwanda across law and cultural studies, I argue that analysing Sometimes in April helps unearth ambiguities within and surrounding the ICTR. Peck’s film and the legal case together communicate a rounded understanding of post-genocide justice to outside audiences, as it is experienced or perceived from local and international perspectives.

Moving their bodies in knowledgeable and professional ways in order to handle and connect affectively with infants entails a large part of child health care nurses' work. We deploy a phenomenological approach to videoanalysis of interaction to analyze an episode of a 1-month-old infant visiting the child health care clinic with their caregiver to have their body assessed for a neonatal stepping. Focusing on the co-movement of the baby and the nurse, we ask: how do various ways of moving as a co-embodied entity allow and corporeally prompt the baby's age-appropriate bodily ability to emerge? We develop the notion of professional interkinesthesia to indicate specific forms of body work of nurses which in this case entails moving together with the baby to make her successfully perform a specific health care task—the stepping. Building on Charles Goodwin's concept of professional vision, we uncover how the nurse moves and touches the infant's body in ways relevant to the institutional task. The study shows that accomplishing “normally” developed neonatal stepping is not work accomplished by the baby alone but requires that the bodies of the baby and the professional move in unison. While neonatal stepping is but one specific type of health care task, we propose that nurses' work entails numerous forms of professional touch and interkinesthesia that make it possible to successfully perform different types of health care operations.

Investments in enabling technologies—including the fifth-generation technology standard for broadband cellular networks (5G), artificial intelligence (AI), and light detection and ranging (LIDAR) technology—are important strategic decisions for firms. This paper asks how inventions that private firms developed with (versus without) public-sector partners differ in their enabling technology trajectory. Using a novel method of machine learning matching, we compare patented technologies generated from more than 30,000 public–private relationships with comparable technologies invented by private firms alone during a 21-year period. To measure the enabling potential of a technology, we introduce a new enabling technology index. The findings show that private-firm relationships with the public sector—in particular cooperative agreements and grants with mission agencies (National Aeronautics and Space Administration and Department of Defense)—are likely starting points for enabling technology trajectories. We thus put a spotlight on organizational arrangements that combine the breadth of exploration (agreements, grants) with deep exploitation in a particular domain (mission agency). A key contribution is a better understanding of the types of private-firm efforts that are associated with enabling technologies. We also challenge the common assumption that enabling technologies have their origins only in public-sector projects and show how private firms are involved. Our significant contribution is to show how private firms can change evolution of ecosystems through technology development.

PurposeGenetic studies of multiple sclerosis (MS) susceptibility and severity have focused on populations of European ancestry. Studying MS genetics in other ancestral groups is necessary to determine the generalisability of these findings. The genetic Association study in individuals from Diverse Ancestral backgrounds with Multiple Sclerosis (ADAMS) project aims to gather genetic and phenotypic data on a large cohort of ancestrally-diverse individuals with MS living in the UK.ParticipantsAdults with self-reported MS from diverse ancestral backgrounds. Recruitment is via clinical sites, online (https://app.mantal.co.uk/adams) or the UK MS Register. We are collecting demographic and phenotypic data using a baseline questionnaire and subsequent healthcare record linkage. We are collecting DNA from participants using saliva kits (Oragene-600) and genotyping using the Illumina Global Screening Array V.3.Findings to dateAs of 3 January 2023, we have recruited 682 participants (n=446 online, n=55 via sites, n=181 via the UK MS Register). Of this initial cohort, 71.2% of participants are female, with a median age of 44.9 years at recruitment. Over 60% of the cohort are non-white British, with 23.5% identifying as Asian or Asian British, 16.2% as Black, African, Caribbean or Black British and 20.9% identifying as having mixed or other backgrounds. The median age at first symptom is 28 years, and median age at diagnosis is 32 years. 76.8% have relapsing–remitting MS, and 13.5% have secondary progressive MS.Future plansRecruitment will continue over the next 10 years. Genotyping and genetic data quality control are ongoing. Within the next 3 years, we aim to perform initial genetic analyses of susceptibility and severity with a view to replicating the findings from European-ancestry studies. In the long term, genetic data will be combined with other datasets to further cross-ancestry genetic discoveries.

In this study, we made reflections of the challenges from inserting graduates into the teaching profession of the aforementioned course at the Universidade Federal Santa Catarina. We developed bibliographic research on the teaching work and the graduation project of this degree, document analysis, data collection with field research, of an exploratory nature, and the data gathering using a questionnaire. The results, still partial, indicate as limiting aspects: the non-inclusion of the qualification of a Licentiate Degree in Educação do Campo (Rural Education) in qualifying processes, the refusal of the graduate by the educational council and/or institutions, or being hired as non-qualified. Some situations were reversed by dialogue and appeals to public notices, an aspect considered as an enhancement. As a contradictory and emerging element to the debate, there is a restriction of the diploma and the job duties being valid only for rural schools. Advancing on the discussions about the degree and insertion in the teaching profession, we pointed out the relevance of the collective organization of the graduates through the movements that fights for Rural Education. Necessary improvements for the transformation of schools and for the future horizon.

Snakes are one of the most diverse vertebrates on the globe, mostly prefer arid zones. Nepal harbors a high unrecognized reptilian diversity. Information on the diversity and distribution of snakes in the western Nepal are derived from relatively from old literatures. This study updated the diversity and distribution of snakes from the Kaski district based on rescuing activities, field survey and literature review. Altogether 40 species of snake from five families were recorded in the Kaski district. The family Colubridae (70%) had the highest species diversity followed by Elapidae (12.5%), Viperidae (12.5%), Pythonidae (2.5 %), and Typhlopidae (2.5 %) respectively. Based on the IUCN global status of snake, 5 % are vulnerable, 5 % data deficient, 27.5 % are Least Concern and 62.5 % are Not Evaluated. Six species were found new distribution records in Kaski. Four species were the species listed on CITES II. Out of 40 species, 27.5% venomous (2.5 % were venomous but not fatal to human, 12.5% were neurotoxic, 12.5% were hemotoxic which are deadly venomous), 20% were weakly venomous and not fatal to human and 50 % were non-venomous. Habitat loss, nest destroyed, road-killed and meaningless killing by the negative perception of people was the most threat to snake in Kaski district.

Clinical trial populations do not fully reflect routine practice. The power of routinely collected data to inform clinical practice is increasingly recognised.The OPTIMISE:MS pharmacovigilance study is a prospective, pragmatic observational study, conducted across 13 UK MS centres. Data were collected at the time of routine clinical visits. The first participant was recruited on 24th May 2019; data were extracted on 11th November 2021.2112 participants were included (median age 44.0 years; 1570 (72%) female; 1981 (94%) relapsing-remitting MS). 639 (30%) were untreated at study entry, 205 (10%) taking interferon beta/copaxone, 1004 (47%) second/third generation DMT first line and 264 (13%) had escalated from a platform DMT. 342 clinical events were reported, of which 108 infections. There was an increased risk of adverse events in people taking second/third generation DMT (RR 3.45, 95%CI 1.57-7.60, p0.01 vs no DMT). Unadjusted Poisson regression demonstrated increased incident adverse events in people taking natalizumab (IRR 5.28, 95%CI 1.41-19.74, p0.05), ocrelizumab (IRR 3.24, 95%CI 1.22-8.62, p0.05), and GA biosimilar (Brabio) (IRR 4.89, 95%CI 1.31-18.21, p0.05) vs no DMT.Routinely collected healthcare data can be used to evaluate DMT safety in people with MS. These data highlight the potential of pragmatic studies to guide understanding of risks and benefits associated with DMT.

We examine a learning-by-doing methodology for iteration of early-stage business ideas known as the “lean startup.” The purpose of this paper is to lay out and test the key assumptions of the method, examining one particularly relevant boundary condition: the composition of the startup team. Using unique and detailed longitudinal data on 152 NSF-supported lean-startup (I-Corps) teams, we find that the key components of the method—hypothesis formulation, probing, and business idea convergence—link up as expected. We also find that team composition is an important boundary condition: business-educated (MBA) members resist the use of the method, but appreciate its value ex-post. Formal training in learning-by-thinking methods thus appears to limit the spread of learning-by-doing methods. In this way, business theory constrains business practice.

In this research, we investigate user experiences with the Laevo exoskeletons in geriatric work. We introduce two studies where Finnish nurses used exoskeletons and identify the requirements and potential restrictions for using exoskeletons in care context. Our results show that nurses’ intentions to use the exoskeletons were mostly associated with perceived usefulness, ergonomics, and enjoyment of use. Also, social environment issues, such as other people’s reactions, are important considerations. Exoskeleton use has varying requirements depending on where it will be implemented. Thus, the end users’ ideas for the design are crucial in enabling exoskeleton use in different sectors of work.

Aim The difficulty of assessing the likelihood of obstructive sleep apnoea (OSA) in children who snore without full-night polysomnography is widely recognised. Our aim was to identify features that were characteristic of two-year-old children with OSA and evaluate whether this information could be used to assess the likelihood of OSA. Methods The study was carried out as part of the Child-Sleep Project, a longitudinal birth cohort study of children born at Tampere University Hospital, Finland. This part of the study focused on the children in the cohort who snored and was carried out between 2013 and 2015. The primary outcomes were measured using parental questionnaires, polysomnography and clinical examinations. Results In total, 52 children participated at a mean age of 27 months (range 23-34). Of these, 32 (44% male) snorers and 20 (70% male) controls. The most significant findings were that children who had OSA demonstrated longer snoring time (P = .003), a greater tendency for mouth breathing (P = .007) and bigger adenoid size (P = .008) than snorers without OSA. Conclusion Snoring time, adenoid tissue size and mouth breathing were important features that identified the likelihood of OSA in snoring toddlers.

Previous research in the social sciences has shown that haptic interaction rituals are critical for maintaining social relationships. However, during the coronavirus (COVID-19) pandemic, ‘social distancing’ was encouraged in order to avoid the spread of disease. Drawing on data from self-ethnography as well as publicly available resources, in this study we explore some new, locally negotiated haptic trajectories to accomplish interaction rituals in the time of coronavirus. First, we present self-ethnographic observations of distancing in face-to-face encounters from our everyday lives. Second, utilizing methods of microanalysis of naturally occurring interaction, we investigate video recordings of the embodied negotiation of space and touch among politicians. We analyze three different ways in which politicians negotiate transitional moves in this haptic ritual when one party initiates a handshake: repairing, declining and apologizing. Our analysis shows that politicians adapt their entire bodies in conjunction with talk, gestures and laughter not only to accomplish the greeting but also to remedy the potentially face-threatening situation of not getting the greeting right. This research has implications for better understanding the spontaneous ability of human beings to invent new ways of engaging with each other. Moreover, it adds to our knowledge of how the materiality of human bodies can impact forms of sociality.

National forest inventories (NFIs) are designed to provide accurate information on forest resources at the national and regional levels, but there is also a demand for such information at smaller spatial scales. Auxiliary data such as satellite imagery have been used to facilitate small-area estimation. The commonly used method, k-nearest neighbour (k-NN), provides a model-based estimator for small areas, but a design-unbiased estimator for the mean square error is not available. Post-stratification (PS) is an alternative approach to using auxiliary information that allows for design-based variance estimation. In a case study using real inventory data of the Finnish NFI, we applied this method to the municipality level to explore the lower limit to the area for which the key forest parameters, forest area and growing stock volumes, can be estimated with sufficient precision. For PS, we employed exogenous forest resources maps based on the previous NFI round. In the municipalities of the two study provinces, the relative standard errors of total volume estimates ranged from 2.3% to 26.9%. They were smaller than 10% for municipalities with an area of 390 km2 or larger, corresponding to approximately 100 or more sample plots on forestland. We also demonstrated the usefulness of design-unbiased variance estimation in showing discrepancies between design-based PS and model-based k-NN estimates.

Since the 1990s, forest resource maps and forest variable estimates for small areas have been produced by combining national forest inventory (NFI) field plot data, optical satellite images and numerical map data. A non-parametric $k$-NN method has frequently been employed. In Finland, such multi-source NFI (MS-NFI) forest variable estimates for municipalities have been produced eight times. A relatively large variation has been observed between subsequent estimates. In this study, a large-scale evaluation of small-area estimates from an MS-NFI conducted in 2013 was carried out in comparison with pure NFI field data-based estimates and error estimates. The proportion of municipalities with significant differences was larger than expected, e.g. over 10% for the mean volume, which indicates systematic error in the small-area estimates. A multi-temporal data fusion combining MS-NFI estimators from three time points—2011, 2013 and 2015—was tested as a means to improve single time point MS-NFI estimates of the mean volumes of growing stock and of tree species groups. A generalized least squares (GLS) technique and unweighted averaging were tested. The improvement was small but consistent when validated against the NFI field data-based estimates for the municipalities. The unweighted averaging worked nearly as well as a GLS estimator.

PMID: 35018829 We investigated the topology of structural brain connectivity networks and its association with outcome after mild traumatic brain injury, a major cause of permanent disability. Eighty-five patients with mild traumatic brain injury underwent magnetic resonance imaging (MRI) twice, about three weeks and eight months after injury, and 30 age-matched orthopedic trauma control subjects were scanned. Outcome was assessed with Extended Glasgow Outcome Scale on average eight months after injury. We performed constrained spherical deconvolution-based probabilistic streamlines tractography on diffusion MRI data and parcellated cortical and subcortical gray matter into 84 regions based on T1-weighted data to reconstruct structural brain connectivity networks weighted by the number of streamlines. Graph theoretical methods were employed to measure network properties in both patients and controls, and correlations between these properties and outcome were calculated. We found no global differences in the network properties between patients with mild traumatic brain injury and orthopedic control subjects at either stage. We found significantly increased betweenness centrality of the right pars opercularis in the chronic stage compared with control subjects, however. Further, both global and local network properties correlated significantly with outcome. Higher normalized global efficiency, degree, and strength as well as lower small-worldness were associated with better outcome. Correlations between the outcome and the local network properties were the most prominent in the left putamen and the left postcentral gyrus. Our results indicate that both global and local network properties provide valuable information about the outcome already in the acute/subacute stage and, therefore, are promising biomarkers for prognostic purposes in mild traumatic brain injury.

Europe's forest provide multiple ecosystem services for societies, ranging from provisioning (e.g. wood) and regulating (e.g. climate mitigation and biodiversity) to cultural (e.g. recreation) services. In this paper, we assess the state and prospects of forest ecosystem services provision in Europe, introducing new data from the European collaborative research projects SINCERE, NOBEL and CLEARING HOUSE, and combining it with findings from the literature. We identify six challenges (1 an insufficient alignment of FES supply and demand, 2 lacking policy integration, 3 ambiguous and conflicting regulatory frameworks, 4 a lack of precise information on FES demand and provision, and innovations to align both, 5 an increasing pressure to adapt to climate change, and 6 a striking diversity constraining European level policy solutions) and three opportunities (1 increasingly heterogenous forest owner objectives potentially matching pluralistic societal demands, 2 diversifying forest enterprises levering innovations in regulating and cultural ecosystem services provision, and 3 the potential of forests to mitigate climate change). Subsequently, we introduce four distinct but complimentary policy pathways for European forest policy to better align forest ecosystem services provision and demand: 1 Better monitoring of FES supply and demand, 2 Enhanced policy integration, 3 Payments for ecosystem services, and 4 Bottom-up participation and learning among ecosystem services innovators. We conclude by emphasizing the momentum that the EU Green Deal unfolds for a future European forest policy to incentivise the provision of multiple forest ecosystem services.

Parkinson's disease (PD) is a debilitating neurodegenerative condition characterized by the loss of dopaminergic neurons within the substantia nigra. The specific molecular mechanisms through which PD-associated neuronal loss occurs remain unclear, and there is no available effective treatment against PD-related neurodegeneration. Resveratrol (RSV) has exhibited promising neuroprotective effects via antioxidant and anti-inflammatory activity. However, its poor bioavailability in the brain represents a challenge for its application in PD treatment. In this study, we synthesized RSV-loaded PLGA nanoparticles (RSV-PLGA-NPs) conjugated with lactoferrin (Lf) to enhance RSV diffusion into the brain and assessed whether this formulation improved the neuroprotective effects of RSV in experimental PD models. The Lf-conjugated RSV-PLGA-NPs (Lf-RSV-PLGA-NPs) exhibited enhanced internalization into SH-SY5Y and human brain microvascular endothelial cells as compared to RSV-PLGA-NPs and free RSV. Further, Lf-RSV-PLGA-NPs were more effective than RSV-PLGA-NPs and free RSV in attenuating the MPP

A new series of fifty-four 2-phenol-4-aryl-6-hydroxyphenylpyridines containing fluorophenyl, trifluoromethylphenyl, and trifluoromethoxy phenyl groups were synthesized and tested for topoisomerase IIα inhibitory and antiproliferative activity against different cancer cell lines in an attempt to look into topoisomerase IIα-targeted prospective anticancer agents to counter the limitations of available treatment options. When compared to positive controls, several compounds 11-12, 37, 50, and 51 showed high antiproliferative activity, while several 4-fluorophenyl substituted compounds 13-14 and 18 showed strong topoisomerase IIα inhibition. Surprisingly, most of the compounds had a significant antiproliferative effect on the HCT15 colorectal adenocarcinoma and T47D breast cancer cell lines. Moreover, compound 12 with para-fluorophenyl at the 4-position and meta-phenolic groups at the 2- and 6-positions inhibited proliferating HeLa cervix adenocarcinoma cells with an IC

Methamphetamine (MA) is a extremely addictive psychostimulant drug with a significant abuse potential. Long-term MA exposure can induce neurotoxic effects through oxidative stress, mitochondrial functional impairment, endoplasmic reticulum stress, the activation of astrocytes and microglial cells, axonal transport barriers, autophagy, and apoptosis. However, the molecular and cellular mechanisms underlying MA-induced neurotoxicity remain unclear. MA abuse increases the chances of developing neurotoxic conditions such as Parkinson's disease (PD), Alzheimer's disease (AD) and other neurotoxic diseases. MA increases the risk of PD by increasing the expression of alpha-synuclein (ASYN). Furthermore, MA abuse is linked to high chances of developing AD and subsequent neurodegeneration due to biological variations in the brain region or genetic and epigenetic variations. To date, there is no Food and Drug Administration (FDA)-approved therapy for MA-induced neurotoxicity, although many studies are being conducted to develop effective therapeutic strategies. Most current studies are now focused on developing therapies to diminish the neurotoxic effects of MA, based on the underlying mechanism of neurotoxicity. This review article highlights current research on several therapeutic techniques targeting multiple pathways to reduce the neurotoxic effects of MA in the brain, as well as the putative mechanism of MA-induced neurotoxicity.

Introduction Neurocritical care focuses on the care of critically ill patients with an acute neurologic disorder and has grown significantly in the past few years. However, there is a lack of data that describe the scope of practice of neurointensivists and epidemiological data on the types of patients and treatments used in neurocritical care units worldwide. To address these issues, we designed a multicenter, international, point-prevalence, cross-sectional, prospective, observational, non-interventional study in the setting of neurocritical care (PRINCE Study). Methods In this manuscript, we analyzed data from the initial phase of the study that included registration, hospital, and intensive care unit (ICU) organizations. We present here descriptive statistics to summarize data from the registration case report form. We performed the Kruskal–Wallis test followed by the Dunn procedure to test for differences in practices among world regions. Results We analyzed information submitted by 257 participating sites from 47 countries. The majority of those sites, 119 (46.3%), were in North America, 44 (17.2%) in Europe, 34 (13.3%) in Asia, 9 (3.5%) in the Middle East, 34 (13.3%) in Latin America, and 14 (5.5%) in Oceania. Most ICUs are from academic institutions (73.4%) located in large urban centers (44% > 1 million inhabitants). We found significant differences in hospital and ICU organization, resource allocation, and use of patient management protocols. The highest nursing/patient ratio was in Oceania (100% 1:1). Dedicated Advanced Practiced Providers are mostly present in North America (73.7%) and are uncommon in Oceania (7.7%) and the Middle East (0%). The presence of dedicated respiratory therapist is common in North America (85%), Middle East (85%), and Latin America (84%) but less common in Europe (26%) and Oceania (7.7%). The presence of dedicated pharmacist is highest in North America (89%) and Oceania (85%) and least common in Latin America (38%). The majority of respondents reported having a dedicated neuro-ICU (67% overall; highest in North America: 82%; and lowest in Oceania: 14%). Conclusion The PRINCE Study results suggest that there is significant variability in the delivery of neurocritical care. The study also shows it is feasible to undertake international collaborations to gather global data about the practice of neurocritical care. Electronic supplementary material The online version of this article (10.1007/s12028-019-00750-3) contains supplementary material, which is available to authorized users.

ObjectiveTo investigate the effect of disease modifying therapies on serological response to SARS-CoV2 vaccines in people with multiple sclerosisMethods473 people with multiple sclerosis from 5 centres provided one or more dried blood spot samples and questionnaires about COVID-19. Information about disease and drug history was extracted from their medical records. Dried blood spots were eluted and tested for antibodies to SARS-CoV2 receptor binding domain. Seropositivity was expressed according to validated cut-off indices. Antibody titers were partitioned into tertiles using data from people on no disease modifying therapy as a reference. We calculated the odds ratio of seroconversion (Univariate logistic regression) and compared quantitative vaccine response (Kruskal Wallis) following SARS-CoV2 vaccine according to disease modifying therapy. We used regression modelling to explore the effect of factors including vaccine timing, treatment duration, age, vaccine type and lymphocyte count on vaccine response.ResultsCompared to no disease modifying therapy, the use of anti-CD20 monoclonal antibodies (odds ratio 0.03; 95% confidence interval 0.01-0.06, pInterpretationSome disease modifying therapies carry a risk of attenuated response to SARS-CoV2 vaccination in people with MS. We provide recommendations for the practical management of this patient group.

The neuropathological hallmark of Parkinson's disease (PD) is the preferential loss of dopaminergic neurons in the substantia nigra and presence of Lewy bodies in the dying neurons. Though specific molecular mechanisms for the neurodegeneration remains to be clarified, mitochondrial dysfunction and increased oxidative stress are major players associated with PD pathogenesis and these pathogenic mechanisms can be reproduced in cells and animals by application of various neurotoxins such as MPP

Anterior cruciate ligament is one of the most common ligaments to get injured especially in athletic population. It is a band of dense connective tissue which arises from the antero-medial aspect of the inter condylar area on the tibial plateau and passes upwards and backwards to attach to the posteromedial aspect of the lateral femoral condyle. There is increasing rate of its reported injuries among athletes in Nepal and surgeons report increased consultations among athletes regarding adequate intervention strategies. Factors like over use, inadequate recovery time, playing surface, fitness incompatibility are involved in the increase of anterior cruciate ligament injury among athletes in Nepal. Treatment approach for anterior cruciate ligament injury is ever evolving with regular studies and innovation, but constant guidance and rehabilitation in an institution-based setting have shown positive feedback in recovery and return to play.

Hypertension is a chronic medical condition which remains inadequately managed everywhere. Medication adherence (MA) is a critical parameter for achieving strict blood pressure (BP) control in patients undergoing antihypertensive therapy (AHT). Good MA is also a key factor determining the success of preventive measures for cardiovascular (CV) risk reduction. So, the objective of this research was to study the medication adherence and blood pressure control among hypertensive patients of Pokhara Valley. A randomized community-based prospective study was conducted in different places of Pokhara. In the study, a structured questionnaire i.e. Brief medication questionnaire (BMQ) with a high sensitivity and specificity was used. Out of 79 respondents enrolled, most of the respondents (n=51, 64.6%) were shown to be non-adherent and only 28 (35.4%) were adherent to the prescribed AHT. The study showed that among adherers, 75% were undergoing monotherapy and 64.3% (n=18) had their BP under control. The comparison between BP control and the different occupation showed that the highest percentage of BP control was achieved in housewives. Most of the respondents were non-adherent to the prescribed AHT which requires special attention of the healthcare providers. Key words: Hypertension, medication adherence, brief medication questionnaire, anti-hypertensive therapy

Purpose The purpose of this paper is to analyze how global and local changes in higher education impact upon writing practices through which doctoral students become academics. The study explores how norms and values of academic writing practice are learned, negotiated and resisted and elucidates how competences related to writing come to determine the academic selves. Design/methodology/approach The study uses memory work, which is a group method that puts attention to written individual memories and their collective analysis and theorizing. The authors offer a comparison of experiences in becoming academics by two generational cohorts (1990s and 2010s) in the same management studies department in a business school. Findings The study indicates that the contextual and temporal enactment of academic writing practice in the department created a situation where implicit and ambiguous criteria for writing competence gradually changed into explicit and narrow ones. The change was relatively slow for two reasons. First, new performance management indicators were introduced over a period of two decades. Second, when the new indicators were gradually introduced, they were locally resisted. The study highlights how the focus, forms and main actors of resistance changed over time. Originality/value The paper offers a detailed account of how exogenous changes in higher education impact upon, over time and cultural space, academic writing practices through which doctoral students become academics. Purpose The purpose of this paper is to analyze how global and local changes in higher education impact upon writing practices through which doctoral students become academics. The study explores how norms and values of academic writing practice are learned, negotiated and resisted and elucidates how competences related to writing come to determine the academic selves. Design/methodology/approach The study uses memory work, which is a group method that puts attention to written individual memories and their collective analysis and theorizing. The authors offer a comparison of experiences in becoming academics by two generational cohorts (1990s and 2010s) in the same management studies department in a business school. Findings The study indicates that the contextual and temporal enactment of academic writing practice in the department created a situation where implicit and ambiguous criteria for writing competence gradually changed into explicit and narrow ones. The change was relatively slow for two reasons. First, new performance management indicators were introduced over a period of two decades. Second, when the new indicators were gradually introduced, they were locally resisted. The study highlights how the focus, forms and main actors of resistance changed over time. Originality/value The paper offers a detailed account of how exogenous changes in higher education impact upon, over time and cultural space, academic writing practices through which doctoral students become academics.

Contains fulltext : 218566pub.pdf (Publisher’s version ) (Closed access) Contains fulltext : 218566pos.pdf (Author’s version postprint ) (Open Access) BACKGROUND: Neurocritical care is devoted to the care of critically ill patients with acute neurological or neurosurgical emergencies. There is limited information regarding epidemiological data, disease characteristics, variability of clinical care, and in-hospital mortality of neurocritically ill patients worldwide. We addressed these issues in the Point PRevalence In Neurocritical CarE (PRINCE) study, a prospective, cross-sectional, observational study. METHODS: We recruited patients from various intensive care units (ICUs) admitted on a pre-specified date, and the investigators recorded specific clinical care activities they performed on the subjects during their first 7 days of admission or discharge (whichever came first) from their ICUs and at hospital discharge. In this manuscript, we analyzed the final data set of the study that included patient admission characteristics, disease type and severity, ICU resources, ICU and hospital length of stay, and in-hospital mortality. We present descriptive statistics to summarize data from the case report form. We tested differences between geographically grouped data using parametric and nonparametric testing as appropriate. We used a multivariable logistic regression model to evaluate factors associated with in-hospital mortality. RESULTS: We analyzed data from 1545 patients admitted to 147 participating sites from 31 countries of which most were from North America (69%, N = 1063). Globally, there was variability in patient characteristics, admission diagnosis, ICU treatment team and resource allocation, and in-hospital mortality. Seventy-three percent of the participating centers were academic, and the most common admitting diagnosis was subarachnoid hemorrhage (13%). The majority of patients were male (59%), a half of whom had at least two comorbidities, and median Glasgow Coma Scale (GCS) of 13. Factors associated with in-hospital mortality included age (OR 1.03; 95% CI, 1.02 to 1.04); lower GCS (OR 1.20; 95% CI, 1.14 to 1.16 for every point reduction in GCS); pupillary reactivity (OR 1.8; 95% CI, 1.09 to 3.23 for bilateral unreactive pupils); admission source (emergency room versus direct admission [OR 2.2; 95% CI, 1.3 to 3.75]; admission from a general ward versus direct admission [OR 5.85; 95% CI, 2.75 to 12.45; and admission from another ICU versus direct admission [OR 3.34; 95% CI, 1.27 to 8.8]); and the absence of a dedicated neurocritical care unit (NCCU) (OR 1.7; 95% CI, 1.04 to 2.47). CONCLUSION: PRINCE is the first study to evaluate care patterns of neurocritical patients worldwide. The data suggest that there is a wide variability in clinical care resources and patient characteristics. Neurological severity of illness and the absence of a dedicated NCCU are independent predictors of in-patient mortality.

With the aim of developing new effective topoisomerase IIα-targeted anticancer agents, we synthesized a series of hydroxy- and halogenated 2,4-diphenyl indeno[1,2-b]pyridinols using a microwave-assisted single step synthetic method and investigated structure-activity relationships. The majority of compounds with chlorophenyl group at 2-position and phenol group at the 4-position of indeno[1,2-b]pyridinols exhibited potent antiproliferative activity and topoisomerase IIα-selective inhibition. Of the 172 compounds tested, 89 showed highly potent and selective topoisomerase IIα inhibition and antiproliferative activity in the nanomolar range against human T47D breast (2.6 nM) cancer cell lines. In addition, mechanistic studies revealed compound 89 is a nonintercalative topoisomerase II poison, and in vitro studies showed it had promising cytotoxic effects in diverse breast cancer cell lines and was particularly effective at inducing apoptosis in T47D cells. Furthermore, in vivo administration of compound 89 had significant antitumor effects in orthotopic mouse model of breast cancer.

Microbiota in the gut affect brain physiology via various pathways, and dysbiosis seems to play a role in the pathogenesis of Parkinson's disease (PD). Probiotics showed pleiotropic effects on functions of the central nervous system via microbiota-gut-brain axis. However, no studies displayed the neuroprotective effects of probiotics in the Parkinson's disease. This study aimed to test the neuroprotective effects of probiotics in two different models of PD. We evaluated neuroprotective effects of a probiotic cocktail containing Lactobacillus rhamnosus GG, Bifidobacterium animalis lactis, and Lactobacillus acidophilus in PD models induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) or rotenone utilizing behavioral tests, immunohistochemistry and neurochemical analysis. To assure the neuroprotection came from increased production of butyrate, we further determined beneficial effects of butyrate in the MPTP-mediated PD model. The probiotic mixture overtly protected the dopaminergic neurons against MPTP neurotoxicity. However, the probiotics downregulated expression of monoamine oxidase (MAO) B in the striatum, which was accompanied by a lower level of 1-methyl-4-phenylpyridinium (MPP+), the main neurotoxic metabolite of MPTP. Thus, we extended the investigation into the rotenone-induced PD model. Rescuing effects of the probiotics were observed in the setup, which came with increased levels of neurotrophic factors and butyrate in the brain. Lactobacillus rhamnosus GG was identified to be a major contributor to the induction of neurotrophic factors and downregulation of MAO B. Finally, we demonstrated that sodium butyrate attenuated MPTP-induced neuronal loss in the nigrostriatal pathway. Probiotics could ameliorate neurodegeneration at least partially by increasing butyrate level. These data highlight the role of probiotics for brain health, and their potential as a preventive measure for neurodegenerative diseases such as PD.

The design and synthesis of a series of thirty-two halogenated 1-tetralone or 6-amino-1-tetralone chalcone derivatives was achieved by the Claisen-Schmidt condensation reaction and were evaluated for their inhibitory effects against ROS production in LPS-stimulated RAW 264.7 macrophages. It was observed that the introduction of amino moiety into 1-tetralone skeleton greatly increased the inhibitory potency compared to corresponding 1-tetralone chalcones. Among the synthesized compounds, compound 18 which consists of 6-amino-1-tetralone skeleton together with o-fluorobenzylidene showed the most potent ROS inhibitory effect with IC50 value of 0.25 ± 0.13 µM. SAR analysis revealed that amino moiety at the 6th position of 1-tetralone chalcones have an important role for exerting the greater ROS inhibitory potency in LPS-stimulated RAW 264.7 macrophages than those exhibited by 1-tetralone chalcones alone.