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A comprehensive set of security technology enablers will be critically required for communication systems for the 6G era of the 2030s. Trustworthiness must be assured across IoT, heterogenous cloud and networks, devices, sub-networks, and applications. The 6G threat vector will be defined by 6G architectural disaggregation, open interfaces and an environment with multiple stakeholders. Broadly decomposed into domains of cyber-resilience, privacy and trust and their respective intersection, we explore relevant security technology enablers including automated software creation and automated closed-loop security operation, privacy preserving technologies, hardware and cloud embedded anchors of trust, quantum-safe security, jamming protection and physical layer security as well as distributed ledger technologies. Artificial intelligence and machine learning (AI/ML) as a key technology enabler will be pervasive and of pivotal relevance across the security technology stack and architecture. A novel vision for a trustworthy Secure Telecom Operation Map is developed as part of the automated closed loop operations paradigm.

360° models are a form of virtual reality (VR) that allow the viewer to view and explore a photorealistic object from multiple locations within the model. Hence, 360° models are an option to perform virtual field trips (VFT) independent of time and location. Thanks to recent technical progress, 360° models are creatable with little effort. Due to their characteristics of visualization and explorability, 360° models appear as excellent learning tools, especially when additional didactic features, such as annotations, are used. The subject of this explorative field study is a 360° model of a waterworks that has been annotated for learning purposes. Data are collected from a total of 55 learners in four cohorts from study programs in environmental engineering and urban studies using a questionnaire that included standardized measurement instruments on motivation, emotion, and usability. Furthermore, the eight learners of cohort 1 are surveyed using semi-structured interviews on learning, operation and features of the 360° model. Overall, a very positive view on learning suitability of 360° models in VFTs is revealed. In addition, further potential for development of the 360° model could be identified. The results indicate that VTFs based on 360° models might be valuable learning tools, because of their applicability without great effort on the part of either the lecturers or the students. VFTs based on 360° models might serve as a supplement to conventional learning activities or in self-directed learning activities.

Background: Cortical, thalamic and hippocampal gray matter atrophy in relapsing–remitting MS (RRMS) is associated cognitive deficits. However, the role of interconnecting white matter pathways including the fornix, cingulum, and uncinate fasciculus (UF) is less well studied. Objective: To assess MS damage to a hippocampal–thalamic–prefrontal network and the relative contributions of its components to specific cognitive domains. Methods: We calculated diffusion tensor fractional anisotropy (FA) in the fornix, cingulum and UF as well as thalamic and hippocampal volumes in 27 RRMS patients and 20 healthy controls. A neuropsychological battery was administered and 4 core tests known to be sensitive to MS changes were used to assess cognitive impairment. To determine the relationships between structure and cognition, all tests were grouped into 4 domains: attention/executive function, processing speed, verbal memory, and spatial memory. Univariate correlations with structural measures and depressive symptoms identified potential contributors to cognitive performance and subsequent linear regression determined their relative effects on performance in each domain. For significant predictors, we also explored the effects of laterality and axial versus radial diffusivity. Results: RRMS patients had worse performance on the Symbol Digit Modalities Test, but no significant impairment in the 4 cognitive domains. RRMS had reduced mean FA of all 3 pathways and reduced thalamic and hippocampal volumes compared to controls. In RRMS we found that thalamic volume and BDI predicted attention/executive function, UF FA predicted processing speed, thalamic volume predicted verbal memory, and UF FA and BDI predicted spatial memory. Conclusions: Hippocampal–thalamic–prefrontal disruption affects cognitive performance in early RRMS with mild to minimal cognitive impairment, confirming both white and gray matter involvement in MS and demonstrating utility in assessing functional networks to monitor cognition.

A key security challenge with biosecurity threats is determining the responsible actor. In this Perspective, the authors review recent developments in using genetic sequence to assign a lab-of-origin and the potential protection it provides against misuse of synthetic biology.

Free Trade Agreements (FTA) are controversial for threatening essential aspects of health, especially access to affordable medicines. The US-Peru FTA required changes in the Peruvian pharmaceutical legislation that resulted in the implementation of the National Drug Policy (NDP) of 2009. The NDP included more robust technical requirements for registration, a Peruvian Good Manufacturing Practices certificate, a longer timeline for drug registration, and an increase in registration fees. This study evaluated the impact of the FTA on the number of registrations and competition in the Peruvian pharmaceutical market.Data for the period January 2005 to April 2014 were provided by the Peruvian drug regulatory authority (Dirección General de Medicamentos, Insumos y Drogas, DIGEMID). A total of 31,114 pharmaceutical products with unique registration numbers were evaluated. Brand drug new registrations decreased from 1789 in 2005 to 455 in 2013, and the number of generic registrations decreased from 621 in 2005 to 114 in 2013. Brand re-registrations also decreased from 714 in 2005 to 58 in 2013. There were 228 brand products awaiting registration in 2009 and 1,908 in 2013. The proportion of products awaiting registration was three times greater for brand than for generic products in 2009–2013.Registration of brand and generic medicines significantly declined after the implementation of the US-Peru FTA in 2009. The decline in the number of registrations was associated with more robust technical requirements, a longer DIGEMID registration timeline, and an increase in registration fees. The stronger registration requirements are expected to increase the quality of the drugs marketed in the country, but also less competition and a reduction in domestic registrations.

Background The United States-Peru Free Trade Agreement required changes in the Peruvian pharmaceutical legislation that resulted in the National Drug Policy (NDP) of 2009. This study evaluated the registration of brand and generic anti-infectives before and after the agreement and implementation of the NDP and assessed the availability of anti-infectives in community pharmacies located in Arequipa-Peru. Methods Anti-infectives registration database, provided by DIGEMID (Peruvian Drug Regulatory Authority), was evaluated from January 2005 to August 2014. Registration status included: new registrations, re-registrations, awaiting registration; or expired, denied, suspended, canceled and disregarded registrations. In addition, ten retail pharmacies located in different socio-economic areas in Arequipa were sampled in August 2014. Descriptive statistics and chi-square test were used for the analysis. Results A total of 6112 anti-infectives registrations were categorized (5007 = antibacterials, 340 = antimycotics, 143 = antimycobacterials, and 622 = antiviral drugs). New registrations for brand and generic anti-infectives decreased from 2005 to 2013 (311 to 60 and 164 to 20 respectively). Re-registrations were from 121 (brand) and 115 (generics) in 2005 to 6 (brand) and 5 (generics) in 2013. Anti-infectives awaiting registration increased from 0 in 2005 to 351 (brand) and 137 (generics) in 2013. The retail pharmacy survey included 1105 anti-infectives. These pharmacies carried 647 (58.6%) products awaiting registration, 74 (6.7%) expired (mostly combination of sulfonamides and trimethoprim followed by penicillin with extended spectrum, and fluoroquinolones), 4 (0.4%) suspended, and 2 (0.2%) denied registrations. Pharmacies in the low socio-economic area of the city had the highest proportion of generics (59.0% vs. 16.1%) from foreign origin (mainly India), and brand anti-infectives from Peruvian manufacturers (68.8% vs. 48.1%). High socio-economic areas had highest proportion of branded anti-infectives (83.9% vs. 41.0%). Conclusions The new NDP reduced the number of brand and generic registrations; generics had the largest decline in registrations. Anti-infectives found in pharmacies located in low-income areas were more likely to be generics, and less likely to be currently registered by DIGEMID. The potential reduction in generic registrations resulting from the implementation of the NDP as a consequence of the bilateral trade agreement could result in lower availability of low cost medicines, but may increase the safety, efficacy and quality of marketed medicines.

Background: Major depression is a chronic disease which often requires long-term antidepressant use. Prescriptions of antidepressants have increased in the past two decades in the US Although current clinical data support the treatment efficacy of antidepressants, early discontinuation of their use by the patient is common. Aim: To identify the treatment experiences of patients, including their perceptions on antidepressant effects, changes in personality, and addiction. Overall goal was to identify factors for larger studies on patterns of antidepressant medication use. Method: This cross-sectional, descriptive study interviewed 45 adults in a large metropolitan city in the US using a structured interview guide that consisted of: demographic characteristics, depression and medication history, antidepressant drug taking behaviors, and antidepressant drug effects. Results: All 45 patients had health insurance. 71.1% of the subjects reported mild to moderate feelings of depression at the time of interview. Almost all (93.3%) patients felt that their antidepressants had made their depression better. 53.3% of patients perceived a change in their personality due to antidepressant use. A third (31%) perceived their antidepressant use to be their choice, while 69% stated it was a necessity. A majority (63.6%) felt they were dependent on their antidepressant, but 88.6% felt they were not addicted to their medication. Conclusions: Overall, important factors on long-term antidepressant use from the patient’s perspective were obtained in this study. Thus these study data can be considered pilot information since it will help to develop tailored intervention studies to improve long-term antidepressant adherence.

Obese women exhibit decreased fertility, high miscarriage rates and dysfunctional corpus luteum (CL), but molecular mechanisms are poorly defined. We hypothesized that weight gain induces alterations in CL gene expression. RNA sequencing was used to identify changes in the CL transcriptome in the vervet monkey (Chlorocebus aethiops) during weight gain. 10 months of high-fat, high-fructose diet (HFHF) resulted in a 20% weight gain for HFHF animals vs. 2% for controls (p = 0.03) and a 66% increase in percent fat mass for HFHF group. Ovulation was confirmed at baseline and after intervention in all animals. CL were collected on luteal day 7-9 based on follicular phase estradiol peak. 432 mRNAs and 9 miRNAs were differentially expressed in response to HFHF diet. Specifically, miR-28, miR-26, and let-7b previously shown to inhibit sex steroid production in human granulosa cells, were up-regulated. Using integrated miRNA and gene expression analysis, we demonstrated changes in 52 coordinately regulated mRNA targets corresponding to opposite changes in miRNA. Specifically, 2 targets of miR-28 and 10 targets of miR-26 were down-regulated, including genes linked to follicular development, steroidogenesis, granulosa cell proliferation and survival. To the best of our knowledge, this is the first report of dietary-induced responses of the ovulating ovary to developing adiposity. The observed HFHF diet-induced changes were consistent with development of a dysfunctional CL and provide new mechanistic insights for decreased sex steroid production characteristic of obese women. MiRNAs may represent novel biomarkers of obesity-related subfertility and potential new avenues for therapeutic intervention.

Investigating the biological bases of social phenotypes is challenging because social behavior is both high-dimensional and richly structured, and biological factors are more likely to influence complex patterns of behavior rather than any single behavior in isolation. The space of all possible patterns of interactions among behaviors is too large to investigate using conventional statistical methods. In order to quantitatively define social phenotypes from natural behavior, we developed a machine learning model to identify and measure patterns of behavior in naturalistic observational data, as well as their relationships to biological, environmental, and demographic sources of variation. We applied this model to extensive observations of natural behavior in free-ranging rhesus macaques, and identified behavioral states that appeared to capture periods of social isolation, competition over food, conflicts among groups, and affiliative coexistence. Phenotypes, represented as the rate of being in each state for a particular animal, were strongly and broadly influenced by dominance rank, sex, and social group membership. We also identified two states for which variation in rates had a substantial genetic component. We discuss how this model can be extended to identify the contributions to social phenotypes of particular genetic pathways.