Search

Abstract In military populations, gene-environment interactions can influence performance and health outcomes. Brain-derived neurotrophic factor (BDNF) is a central nervous system protein that is important for neuronal function and synaptic plasticity. A BDNF single nucleotide polymorphism, rs6265, leads to an amino acid substitution of valine (Val) with methionine (Met) at codon 66 (Val66Met), which may influence an individual’s response to occupational stress, and predispose military members to psychological disorders. Telomere length (TL), a novel measure of biological aging, can be used as a biomarker of stress. Accordingly, telomere shortening may be a surrogate indicator of physiological weathering due to chronic disease and stressful life events. To increase our understanding about the potential effect of the Val66Met mutation on the human stress response, we evaluated the relationships between Val66Met, TL, and mental health symptoms in a military population. In this pilot study (N = 164), we observed an association between Val66Met and reduced TL (p = 0.048). There was no relationship between Val66Met and mental health symptoms. These results support the investigation of gene-environment interactions, and their potential influence on TL due to occupational stress such as military service.

Abstract Cellular responses to TNF are inherently heterogeneous within an isogenic cell population and across different cell types. TNF promotes cell survival by activating pro-inflammatory NF-κB and MAPK signalling pathways but may also trigger apoptosis and necroptosis. Following TNF stimulation, the fate of individual cells is governed by the balance of pro-survival and pro-apoptotic signalling pathways. To elucidate the molecular mechanisms driving heterogenous responses to TNF, quantifying TNF/TNFR1 signalling at the single-cell level is crucial. Fluorescence live-cell imaging techniques offer real-time, dynamic insights into molecular processes in single cells, allowing for detection of rapid and transient changes, as well as identification of subpopulations, that are likely to be missed with traditional endpoint assays. Whilst fluorescence live-cell imaging has been employed extensively to investigate TNF-induced inflammation and TNF-induced cell death, it has been underutilised in studying the role of TNF/TNFR1 signalling pathway crosstalk in guiding cell-fate decisions in single cells. Here, we outline the various opportunities for pathway crosstalk during TNF/TNFR1 signalling and how these interactions may govern heterogenous responses to TNF. We also advocate for the use of live-cell imaging techniques to elucidate the molecular processes driving cell-to-cell variability in single cells. Understanding and overcoming cellular heterogeneity in response to TNF and modulators of the TNF/TNFR1 signalling pathway could lead to the development of targeted therapies for various diseases associated with aberrant TNF/TNFR1 signalling, such as rheumatoid arthritis, metabolic syndrome, and cancer.

Objective To develop evidence-based guidance for topical steroid use in paediatric eosinophilic oesophagitis (pEoE) in the UK for both induction and maintenance treatment.Methods A systematic literature review using Cochrane guidance was carried out by the British Society of Paediatric Gastroenterology, Hepatology and Nutrition (BSPGHAN) Eosinophilic Oesophagitis (EoE) Working Group (WG) and research leads to determine the evidence base for preparation, dosing and duration of use of swallowed topical steroid (STS) formulations in EoE. Seven themes relating to pEoE were reviewed by the WG, alongside the Cochrane review this formed the evidence base for consensus recommendations for pEoE in the UK. We provide an overview of practical considerations including treatment regimen and dosing. Oral viscous budesonide (OVB) and, if agreed by local regulatory committees, orodispersible budesonide (budesonide 1 mg tablets) were selected for ease of use and with most improvement in histology. A practical ‘how to prepare and use’ OVB appendix is included. Side effects identified included candidiasis and adrenal gland suppression. The use of oral systemic steroids in strictures is discussed briefly.Results 2638 citations were identified and 18 randomised controlled trials were included. Evidence exists for the use of STS for induction and maintenance therapy in EoE, especially regarding histological improvement. Using the Appraisal of Guidelines, Research and Evaluation criteria, dosing of steroids by age (0.5 mg two times per day

IntroductionThe Clinical-Functional Vulnerability Index (IVCF-20) is a validated multidimensional instrument that has been used in Brazil to evaluate functional disability in frail older adults. The main aim of this study was to assess frailty using this novel screening tool. In addition, to investigate whether frailty was associated with cognitive impairment and functional disability in older adults with affective disorders.MethodsParticipants included were over 60 years old, with affective disorders (depressive or anxiety disorders), from two specialized outpatient clinics. The sample was comprised of 46 patients (30% of a total from 153). The following instruments were applied: Clock Drawing Test (CDT), Mini Mental State Examination (MMSE); Verbal Fluency Test (VFT); Pfeffer Questionnaire or Functional Assessment Questionnaire (FAQ); Katz Index; Geriatric Depression Scale (GDS-15); Geriatric Anxiety Inventory (GAI), and IVCF-20 as well as sociodemographic and clinical questionnaires. The association between the variables of interest was estimated using Spearman correlation.ResultsThis study found a negative correlation between frailty and cognitive decline (MMSE; rs = −0.58; p

Raw data obtained by ultra-high pressure liquid chromatography–mass spectrometry, and processed lipid compositional data are presented alongside detailed methodology. Data were obtained as bovine liver lipid extract oxidizes, initiated by 2,2′-Azobis(2-amidinopropane) dihydrochloride, at 0, 6 and 24 h post initiation. Lipid oxidation data in the presence and absence of some supplements with antioxidant properties was obtained. The supplements used were grape seed extract, pine bark extract, milk thistle extract, hawthorn extract and turmeric extract.

Summary: Synaptic plasticity is a complex phenomenon involving multiple biochemical processes that operate on different timescales. Complexity can greatly increase memory capacity when the variables characterizing the synaptic dynamics have limited precision, as shown in simple memory retrieval problems involving random patterns. Here we turn to a real-world problem, face familiarity detection, and we show that synaptic complexity can be harnessed to store in memory a large number of faces that can be recognized at a later time. The number of recognizable faces grows almost linearly with the number of synapses and quadratically with the number of neurons. Complex synapses outperform simple ones characterized by a single variable, even when the total number of dynamical variables is matched. Complex and simple synapses have distinct signatures that are testable in experiments. Our results indicate that a system with complex synapses can be used in real-world tasks such as face familiarity detection.

Dietary supplements containing plant extracts are often marketed as having antioxidant properties. Using complex lipid mixtures derived from cellular tissue, we perform a targeted lipidomic assessment of the antioxidant activity of five plant extract supplements. Formulations derived from grape seed, milk thistle, pine bark, turmeric and hawthorn extract were evaluated. Overall, we find evidence to suggest that all supplements suppressed in vitro lipid oxidation to some degree. Suppression of oxidation was most effective in the dominant lipid classes, phosphatidylcholine (PC) and phosphatidylethanolamine (PE), which contain significant numbers of polyunsaturated lipids. Under the conditions of study, grape seed extract supplement was the most effective antioxidant showing statistically significant suppression of lipid oxidation in 11 of the 15 lipid classes quantified. Lipid compositional changes and metrics such as the PC: PE ratio and the double bond index were determined to provide an insight into the effect of oxidative stress and antioxidants on collective membrane properties. Finally, the likely stress that in vivo lipid oxidation could cause to cells, and the mitigating effects of supplements in this context, is also discussed.

Background: Causes of death during the coronavirus disease 2019 (COVID-19) pandemic ranhttp://crossmark.crossref.org/dialog/?doi=10.4102/ajlm.v11i1.1766=pdfdate_stamp=2022-11-23ge from direct consequences of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection to deaths unrelated to SARS-CoV-2. Another feature of the pandemic is the post-mortem testing for SARS-CoV-2. Understanding these aspects of COVID-19 are essential in planning and limiting the impact of SARS-CoV-2 virus on healthcare systems. Objective: This study investigated the underlying causes of death and the presence of SARS-CoV-2 in bodies received at the 37 Military Hospital, Accra, Ghana, during the COVID-19 pandemic. Methods: The study was conducted from 4–27 May 2020. Deceased patients that met the inclusion criteria were prospectively selected during the expanded surveillance period for SARS-CoV-2 testing, autopsy and determination of underlying and immediate cause of death. Results: A total of 161 deceased patients were analysed with 53 autopsies. The overall positive test rate for SARS-CoV-2 was 14.9% (24/161 patients), with a positive rate of 5.0% (8/161 patients) for nasopharyngeal samples and 30.2% (16/161 patients) for bronchopulmonary samples. The underlying causes of death were not related to SARS-CoV-2 infection in 85.1% (137/161) of patients, SARS-CoV-2-associated 12.4% (20/161) and SARS-CoV-2-induced in 2.5% (4/161). Cardiovascular complications formed the most common cause of death in patients with or without SARS-CoV-2. Conclusion: There was a high positive rate of SARS-CoV-2 in post-mortem cases. However, most deaths were not caused by SARS-CoV-2 but by cardiovascular complications. The high rate of bronchopulmonary positive results for SARS-CoV-2 requires that autopsies be done in suspicious cases with negative nasopharyngeal sampling.

Abstract Background To explore the mutual relationship between multimorbidity, mental illness and frailty, we have set-up the Multimorbidity and Mental health Cohort Study in FRAILty and Aging (MiMiCS-FRAIL) cohort. At the population level, multimorbidity, frailty and late-life depression are associated with similar adverse outcomes (i.e. falls, disability, hospitalization, death), share the same risk factors, and partly overlap in their clinical presentation. Moreover, these three variables may share a common underlying pathophysiological mechanism like immune-metabolic dysregulation. The overall objectives of MiMiCS-FRAIL are 1) to explore (determinants of) the cross-sectional and longitudinal relationship between multimorbidity, depression, and frailty among non-demented geriatric outpatients; 2) to evaluate molecular levels of senoinflammation as a broad pathophysiological process underlying these conditions; and 3) to examine adverse outcomes of multimorbidity, frailty and depression and their interconnectedness. Methods MiMiCS-FRAIL is an ongoing observational cohort study of geriatric outpatients in Brazil, with an extensive baseline assessment and yearly follow-up assessments. Each assessment includes a comprehensive geriatric assessment to identify multimorbidity and geriatric syndromes, a structured psychiatric diagnostic interview and administration of the PHQ-9 to measure depression, and several frailty measures (FRAIL, Physical Phenotype criteria, 36-item Frailty Index). Fasten blood samples are collected at baseline to assess circulating inflammatory and anti-inflammatory cytokines, leukocytes' subpopulations, and to perform immune-metabolic-paired miRome analyses. The primary outcome is death and secondary outcomes are the number of falls, hospital admissions, functional ability, well-being, and dementia. Assuming a 5-year mortality rate between 25 and 40% and a hazard rate varying between 1.6 and 2.3 for the primary determinants require a sample size between 136 and 711 patients to detect a statistically significant effect with a power of 80% (beta = 0.2), an alpha of 5% (0.05), and an R2 between the predictor (death) and all covariates of 0.20. Local ethical board approved this study. Discussion Frailty might be hypothesized as a final common pathway by which many clinical conditions like depression and chronic diseases (multimorbidity) culminate in many adverse effects. The MiMiCS-FRAIL cohort will help us to understand the interrelationship between these variables, from a clinical perspective as well as their underlying molecular signature.

Adult forms of inflammatory bowel disease (IBD) are of a polygenic nature, but paediatric and very early onset (VEO) IBD also occur as monogenic forms. Here, using whole exome sequencing, the authors explore both the monogenic and polygenic contribution to VEO-IBD and characterize a rare somatic mosaic VEO-IBD patient.

Wearable devices are becoming more and more prevalent in our daily lives as people become more curious about how well they are doing in monitoring, improving, or maintaining their health and fitness. Fitness trackers and smartwatches have become almost ubiquitous, so these devices have begun to play a critical role in forensic investigations. In this paper, the authors conducted a forensic analysis of the controlling applications for three popular fitness bands and smartwatches (i.e., Amazon Halo, Garmin Connect, and Mobvoi) on an Android smartphone device to (1) provide forensic investigators with a road-map of forensically relevant data that are stored within these applications and (2) highlight any privacy concerns that the stored data within these applications may present to the applications’ users. Our findings indicate that the three fitness applications store a wealth of user data. In particular, the Amazon Halo app stores daily, weekly, and monthly activity-related data for at least the last 13 days. The user’s Tone Analysis results were also recovered. The Garmin Connect application also records detailed user activity information, as it was possible to recover the last 15 days worth of user activity data. The Garmin Connect user’s general location was also determined via the application’s weather notification feature. Lastly, the Mobvoi application records all data points from the time the device is first used until the last time the device is used. These data points may include heart rates taken every 5 min and step counts. Our findings highlight the possibility of collecting personally identifiable information about users of these devices and apps, including their profile information, habits, location, and state of mind. These findings would be pertinent to forensic investigators in the event that these or similar applications are part of an investigation.

BACKGROUND Individuals recovering from COVID-19 frequently experience persistent respiratory ailments, which are key elements of postacute sequelae of SARS-CoV-2 infection (PASC); however, little is known about the underlying biological factors that may direct lung recovery and the extent to which these are affected by COVID-19 severity.METHODS We performed a prospective cohort study of individuals with persistent symptoms after acute COVID-19, collecting clinical data, pulmonary function tests, and plasma samples used for multiplex profiling of inflammatory, metabolic, angiogenic, and fibrotic factors.RESULTS Sixty-one participants were enrolled across 2 academic medical centers at a median of 9 weeks (interquartile range, 6–10 weeks) after COVID-19 illness: n = 13 participants (21%) had mild COVID-19 and were not hospitalized, n = 30 participants (49%) were hospitalized but were considered noncritical, and n = 18 participants (30%) were hospitalized and in the intensive care unit (ICU). Fifty-three participants (85%) had lingering symptoms, most commonly dyspnea (69%) and cough (58%). Forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), and diffusing capacity for carbon monoxide (DLCO) declined as COVID-19 severity increased (P < 0.05) but these values did not correlate with respiratory symptoms. Partial least-squares discriminant analysis of plasma biomarker profiles clustered participants by past COVID-19 severity. Lipocalin-2 (LCN2), MMP-7, and HGF identified by our analysis were significantly higher in the ICU group (P < 0.05), inversely correlated with FVC and DLCO (P < 0.05), and were confirmed in a separate validation cohort (n = 53).CONCLUSION Subjective respiratory symptoms are common after acute COVID-19 illness but do not correlate with COVID-19 severity or pulmonary function. Host response profiles reflecting neutrophil activation (LCN2), fibrosis signaling (MMP-7), and alveolar repair (HGF) track with lung impairment and may be novel therapeutic or prognostic targets.Funding National Heart, Lung, and Blood Institute (K08HL130557 and R01HL142818), American Heart Association (Transformational Project Award), the DeLuca Foundation Award, a donation from Jack Levin to the Benign Hematology Program at Yale University, and Duke University.

The role of the pneumococcal polysaccharide capsule is largely unclear for Streptococcus pneumoniae keratitis, an ocular inflammatory disease that develops as a result of bacterial infection of the cornea. In this study, capsule-deficient strains were compared to isogenic parent strains in their ability to adhere to human corneal epithelial cells. One isogenic pair was further used in topical ocular infection of mice to assess the contribution of the capsule to keratitis. The results showed that non-encapsulated pneumococci were significantly more adherent to cells, persisted in significantly higher numbers on mouse corneas in vivo, and caused significant increases in murine ocular IL9, IL10, IL12-p70, MIG, and MIP-1-gamma compared to encapsulated S. pneumoniae. These findings indicate that the bacterial capsule impedes virulence and the absence of capsule impacts inflammation following corneal infection.

Abstract Background Following injury to the central nervous system, increased microglia, secretion of pro- and anti-inflammatory cytokines, and altered blood-brain barrier permeability, a hallmark of degeneration, are observed at and immediately adjacent to the injury site. However, few studies investigate how regions remote from the primary injury could also suffer from inflammation and secondary degeneration. Methods Adult female Piebald-Viral-Glaxo (PVG) rats underwent partial transection of the right optic nerve, with normal, age-matched, unoperated animals as controls. Perfusion-fixed brains and right optic nerves were harvested for immunohistochemical assessment of inflammatory markers and blood-brain barrier integrity; fresh-frozen brains were used for multiplex cytokine analysis. Results Immediately ventral to the optic nerve injury, immunointensity of both the pro-inflammatory biomarker inducible nitric oxide synthase (iNOS) and the anti-inflammatory biomarker arginase-1 (Arg1) increased at 7 days post-injury, with colocalization of iNOS and Arg1 immunoreactivity within individual cells. CD11b+ and CD45+ cells were increased 7 days post-injury, with altered BBB permeability still evident at this time. In the lower and middle optic tract and superior colliculus, IBA1+ resident microglia were first increased at 3 days; ED1+ and CD11b+ cells were first increased in the middle and upper tract and superior colliculus 7 days post-injury. Increased fibrinogen immunoreactivity indicative of altered BBB permeability was first observed in the contralateral upper tract at 3 days and middle tract at 7 days post-injury. Multiplex cytokine analysis of brain homogenates indicated significant increases in the pro-inflammatory cytokines, IL-2 and TNFα, and anti-inflammatory cytokine IL-10 1 day post-injury, decreasing to control levels at 3 days for TNFα and 7 days for IL-2. IL-10 was significantly elevated at 1 and 7 days post-injury with a dip at 3 days post-injury. Conclusions Partial injury to the optic nerve induces a complex remote inflammatory response, characterized by rapidly increased pro- and anti-inflammatory cytokines in brain homogenates, increased numbers of IBA1+ cells throughout the visual pathways, and increased CD11b+ and ED1+ inflammatory cells, particularly towards the synaptic terminals. BBB permeability can increase prior to inflammatory cell infiltration, dependent on the brain region.

Posterior capsule opacification (PCO) is the most common complication arising from the corrective surgery used to treat cataract patients. PCO arises when lens epithelial cells (LEC) residing in the capsular bag post-surgery undergo hyper-proliferation and transdifferentiation into myofibroblasts, migrating from the posterior capsule over the visual axis of the newly implanted intraocular lens (IOL). The developmental pathways underlying PCO are yet to be fully understood and the current literature is contradictory regarding the impact of the recognised risk factors of PCO. The aim of this review is firstly to collate the known biochemical pathways that lead to PCO development, providing an up-to-date chronological overview from surgery to established PCO formation. Secondly, the risk factors of PCO are evaluated, focussing on the impact of IOLs’ properties. Finally, the latest experimental model designs used in PCO research are discussed to demonstrate the ongoing development of clinical PCO models, the efficacy of newly developed IOL technology, and potential therapeutic interventions. This review will contribute to current PCO literature by presenting an updated overview of the known developmental pathways of PCO, an evaluation of the impact of the risk factors underlying its development, and the latest experimental models used to investigate PCO. Furthermore, the review should provide developmental routes for research into the investigation of potential therapeutic interventions and improvements in IOL design in the aid of preventing PCO for new and existing patients.

Abstract Background Following partial injury to the central nervous system, cells beyond the initial injury site undergo secondary degeneration, exacerbating loss of neurons, compact myelin and function. Changes in Ca2+ flux are associated with metabolic and structural changes, but it is not yet clear how flux through specific ion channels contributes to the various pathologies. Here, partial optic nerve transection in adult female rats was used to model secondary degeneration. Treatment with combinations of three ion channel inhibitors was used as a tool to investigate which elements of oxidative and structural damage related to long term functional outcomes. The inhibitors employed were the voltage gated Ca2+ channel inhibitor Lomerizine (Lom), the Ca2+ permeable AMPA receptor inhibitor YM872 and the P2X7 receptor inhibitor oxATP. Results Following partial optic nerve transection, hyper-phosphorylation of Tau and acetylated tubulin immunoreactivity were increased, and Nogo-A immunoreactivity was decreased, indicating that axonal changes occurred acutely. All combinations of ion channel inhibitors reduced hyper-phosphorylation of Tau and increased Nogo-A immunoreactivity at day 3 after injury. However, only Lom/oxATP or all three inhibitors in combination significantly reduced acetylated tubulin immunoreactivity. Most combinations of ion channel inhibitors were effective in restoring the lengths of the paranode and the paranodal gap, indicative of the length of the node of Ranvier, following injury. However, only all three inhibitors in combination restored to normal Ankyrin G length at the node of Ranvier. Similarly, HNE immunoreactivity and loss of oligodendrocyte precursor cells were only limited by treatment with all three ion channel inhibitors in combination. Conclusions Data indicate that inhibiting any of a range of ion channels preserves certain elements of axon and node structure and limits some oxidative damage following injury, whereas ionic flux through all three channels must be inhibited to prevent lipid peroxidation and preserve Ankyrin G distribution and OPCs.

Studies have shown that a combined application of several ion channel inhibitors immediately after central nervous system injury can inhibit secondary degeneration. However, for clinical use, it is necessary to determine how long after injury the combined treatment of several ion channel inhibitors can be delayed and efficacy maintained. In this study, we delivered Ca2+ entry-inhibiting P2X7 receptor antagonist oxidized-ATP and AMPA receptor antagonist YM872 to the optic nerve injury site via an iPRECIO@ pump immediately, 6 hours, 24 hours and 7 days after partial optic nerve transection surgery. In addition, all of the ion channel inhibitor treated rats were administered with calcium channel antagonist lomerizine hydrochloride. It is important to note that as a result of implantation of the particular pumps required for programmable delivery of therapeutics directly to the injury site, seromas occurred in a significant proportion of animals, indicating infection around the pumps in these animals. Improvements in visual function were observed only when treatment was delayed by 6 hours; phosphorylated Tau was reduced when treatment was delayed by 24 hours or 7 days. Improvements in structure of node/paranode of Ranvier and reductions in oxidative stress indicators were also only observed when treatment was delayed for 6 hours, 24 hours, or 7 days. Benefits of ion channel inhibitors were only observed with time-delayed treatment, suggesting that delayed therapy of Ca2+ ion channel inhibitors produces better neuroprotective effects on secondary degeneration, at least in the presence of seromas.

The raising accessibility of Unmanned Aerial Vehicles (UAVs), colloquially known as drones, is rapidly increasing. Recent studies have discussed challenges that may come in tow with the growing use of this technology. These studies note that in-depth examination is required, especially when addressing challenges that carry a high volume of software data between sensors, actuators, and control commands. This work underlines static and live digital evidence traceability challenges to further enhance the UAV incident response plan. To study the live UAV forensic traceability issues, we apply the ‘purple-teaming’ exercise on small UAVs while conducting UAV forensic examination to determine technical challenges related to data integrity and repeatability. In addition, this research highlights current static technical challenges that could pose more challenges in justifying the discovered digital evidence. Additionally, this study discusses potential drone anti-forensic techniques and their association with the type of use, environment, attack vector, and level of expertise. To this end, we propose the UAV Kill Chain and categorize the impact and complexity of all highlighted challenges based on the conducted examination and the presented scientific contribution in this work. To the best of our knowledge, there has not been any contribution that incorporates ‘Purple-Teaming’ tactics to evaluate UAV-related research in cybersecurity and digital forensics. This work also proposes a categorization model that classifies the discovered UAV static and live digital evidence challenges based on their complexity and impact levels.

Digital evidence plays a crucial role in child pornography investigations. However, in the following case study, the authors argue that the behavioral analysis or “profiling” of digital evidence can also play a vital role in child pornography investigations. The following case study assessed the Internet Browsing History (Internet Explorer Bookmarks, Mozilla Bookmarks, and Mozilla History) from a suspected child pornography user’s computer. The suspect in this case claimed to be conducting an ad hoc law enforcement investigation. After the URLs were classified (Neutral; Adult Porn; Child Porn; Adult Dating sites; Pictures from Social Networking Profiles; Chat Sessions; Bestiality; Data Cleaning; Gay Porn), the Internet history files were statistically analyzed to determine prevalence and trends in Internet browsing. First, a frequency analysis was used to determine a baseline of online behavior. Results showed 54% (n = 3205) of the URLs were classified as “neutral” and 38.8% (n = 2265) of the URLs were classified as a porn website. Only 10.8% of the URLs were classified as child pornography websites. However when the IE history file was analyzed by visit, or “hit,” count, the Pictures/Profiles (31.5%) category had the highest visit count followed by Neutral (19.3%), Gay Porn (17%), and Child Porn (16.6%). When comparing the frequency of URLs to the Hit Count for each pornography type, it was noted that the accused was accessing gay porn, child porn, chat rooms, and picture profiles (i.e., from Facebook) more often than adult porn and neutral websites. The authors concluded that the suspect in this case was in fact a child pornography user and not an ad hoc investigator, and the findings from the behavioral analysis were admitted as evidence in the sentencing hearing for this case. The authors believe this case study illustrates the ability to conduct a behavioral analysis of digital evidence. More work is required to further validate the behavioral analysis process described, but the ability to infer the predilection for being a consumer of child pornography based on Internet artifacts may prove to be a powerful tool for investigators.

The rapid pace of invention in technology and the evolution of network communication has produced a new lifestyle with variety of opportunities and challenges. Remotely Piloted Aerial Systems (RPAS) technology, which includes drones, is one example of a recently invented technology that requires the collection of a solid body of defensible and admissible evidence to help eliminate potential real-world threats posed by their use. With the advent of smartphones, there has been an increase in digital forensic investigation processes developed to assist specialized digital forensic investigators in presenting forensically sound evidence in the courts of law. Therefore, it is necessary to apply digital forensic techniques and procedures to different types of RPASs in order to create a line of defense against new challenges, such as aerial-related incidents, introduced by the use of these technologies. Drone operations by bad actors are rapidly increasing and these actors are constantly developing new approaches. These criminal operations include invasion of privacy, drug smuggling, and terrorist activities. Additionally, drone crashes and incidents raise significant concerns. In this paper, we propose a technical forensic process consisting of ten technical phases for the analysis of RPAS forensic artifacts, which can reduce the complexity of the identification and investigation of drones. Using the proposed technical process, we analyze drone images using the Computer Forensics Reference Datasets (CFReDS) and present results for the Typhoon H aerial vehicle manufactured by Yuneec, Inc. Furthermore, this paper explores the availability and value of digital evidence that would allow a more practical digital investigation to be able to build an evidence-based experience. Therefore, we particularly focus on developing a technical drone investigation process that can be applied to various types of drones.

Species delimitation of geographically isolated forms is a long-standing problem in less studied insect groups. Often taxonomic decisions are based directly on morphologic variation, and lack a discussion regarding sample size and the efficiency of migration barriers or dispersal/migration capacity of the studied species. These problems are here exemplified in a water beetle complex from the Bering Sea region that separates North America from Eurasia. Only a few sampled specimens occur from this particular area and they are mostly found in museum and private collections. Here we utilize the theory of integrated taxonomy to discuss the speciation of the Holarctic Colymbetes paykulli water beetle complex, which historically has included up to five species of which today only two are recognized. Three delimitation methods are used; landmark based morphometry of body shape, variation in reticulation patterns of the pronotum exo-skeleton and sequence variation of the partial mitochondrial gene Cyt b. Our conclusion is that the Palearctic and Nearctic populations of C. paykulli are given the status of separate species, based on the fact that all methods showed significant separation between populations. As a consequence the name of the Palearctic species is C. paykulli Erichson and the Nearctic species should be known as C. longulus LeConte. There is no clear support for delineation between Palearctic and Nearctic populations of C. dahuricus based on mtDNA. However, significant difference in size and reticulation patterns from the two regions is shown. The combined conclusion is that the C. dahuricus complex needs a more thorough investigation to fully disentangle its taxonomic status. Therefore it is here still regarded as a Holarctic species. This study highlights the importance to study several diagnosable characters that has the potential to discriminate evolutionary lineage during speciation.

With the proliferation of digital based evidence, the need for the timely identification, analysis and interpretation of digital evidence is becoming more crucial. In many investigations critical information is required while at the scene or within a short period of time - measured in hours as opposed to days. The traditional cyber forensics approach of seizing a system(s)/media, transporting it to the lab, making a forensic image(s), and then searching the entire system for potential evidence, is no longer appropriate in some circumstances. In cases such as child abductions, pedophiles, missing or exploited persons, time is of the essence. In these types of cases, investigators dealing with the suspect or crime scene need investigative leads quickly; in some cases it is the difference between life and death for the victim(s). The Cyber Forensic Field Triage Process Model (CFFTPM) proposes an onsite or field approach for providing the identification, analysis and interpretation of digital evidence in a short time frame, without the requirement of having to take the system(s)/media back to the lab for an in-depth examination or acquiring a complete forensic image(s). The proposed model adheres to commonly held forensic principles, and does not negate the ability that once the initial field triage is concluded, the system(s)/storage media be transported back to a lab environment for a more thorough examination and analysis. The CFFTPM has been successfully used in various real world cases, and its investigative importance and pragmatic approach has been amply demonstrated. Furthermore, the derived evidence from these cases has not been challenged in the court proceedings where it has been introduced. The current article describes the CFFTPM in detail, discusses the model’s forensic soundness, investigative support capabilities and practical considerations.

Red/near-infrared irradiation therapy (R/NIR-IT) delivered by laser or light-emitting diode (LED) has improved functional outcomes in a range of CNS injuries. However, translation of R/NIR-IT to the clinic for treatment of neurotrauma has been hampered by lack of comparative information regarding the degree of penetration of the delivered irradiation to the injury site and the optimal treatment parameters for different CNS injuries. We compared the treatment efficacy of R/NIR-IT at 670 nm and 830 nm, provided by narrow-band LED arrays adjusted to produce equal irradiance, in four in vivo rat models of CNS injury: partial optic nerve transection, light-induced retinal degeneration, traumatic brain injury (TBI) and spinal cord injury (SCI). The number of photons of 670 nm or 830 nm light reaching the SCI injury site was 6.6% and 11.3% of emitted light respectively. Treatment of rats with 670 nm R/NIR-IT following partial optic nerve transection significantly increased the number of visual responses at 7 days after injury (P ≤ 0.05); 830 nm R/NIR-IT was partially effective. 670 nm R/NIR-IT also significantly reduced reactive species and both 670 nm and 830 nm R/NIR-IT reduced hydroxynonenal immunoreactivity (P ≤ 0.05) in this model. Pre-treatment of light-induced retinal degeneration with 670 nm R/NIR-IT significantly reduced the number of Tunel+ cells and 8-hydroxyguanosine immunoreactivity (P ≤ 0.05); outcomes in 830 nm R/NIR-IT treated animals were not significantly different to controls. Treatment of fluid-percussion TBI with 670 nm or 830 nm R/NIR-IT did not result in improvements in motor or sensory function or lesion size at 7 days (P>0.05). Similarly, treatment of contusive SCI with 670 nm or 830 nm R/NIR-IT did not result in significant improvements in functional recovery or reduced cyst size at 28 days (P>0.05). Outcomes from this comparative study indicate that it will be necessary to optimise delivery devices, wavelength, intensity and duration of R/NIR-IT individually for different CNS injury types.

Prenatal alcohol exposure may have adverse effects on the developing foetus resulting in significant growth restriction, characteristic craniofacial features, and central nervous system dysfunction. The toxic effects of alcohol on the developing brain are well recognised. However, little is known about the effects of alcohol on the developing gastrointestinal tract or their mechanism. There are few case reports showing an association between foetal alcohol syndrome and gastrointestinal neuropathy. We report a rare association between foetal alcohol syndrome and severe gastrooesophageal reflux disease in an infant who ultimately required fundoplication to optimise her growth and nutrition. The child had failed to respond to maximal medical treatment (domperidone and omeprazole), high calorie feeds, PEG feeding, or total parenteral nutrition. The effect of alcohol on the developing foetus is not limited to the central nervous system but also can have varied and devastating effects on the gastrointestinal tract.

The repeated occurrence of habitat-specific polyphyletic evolved ecotypes throughout the ranges of widely distributed species implies that multiple, independent and parallel selection events have taken place. Ecological transitions across altitudinal gradients over short geographical distances are often associated with variation in habitat-related fitness, these patterns suggest the action of strong selective forces. Genetic markers will therefore contribute differently to differences between ecotypes in local hybrid zones. Here we have studied the adaptive divergence between ecotypes of the water beetle Agabus bipustulatus along several parallel altitudinal gradients in northern Scandinavia. This water beetle is well known for its remarkable morphological variation associated with mountain regions throughout the western Palaearctic. Two morphological ecotypes are recognised: a montane type with reduced flight muscles and a lowland type with fully developed muscles. Using a multilocus survey of allozyme variation and a morphological analysis with landmark-based morphometrics, across thirty-three populations and seven altitudinal gradients, we studied the local adaptive process of gene flow and selection in detail. Populations were sampled at three different elevations: below, at and above the tree line. The results indicate that the levels of divergence observed between ecotypes in morphology and allele frequencies at α-Glycerophosphate dehydrogenase relative to those shown by neutral molecular markers reflects local diversifying selection in situ. Four main lines of evidence are shown here: (1) A repeated morphological pattern of differentiation is observed across all altitudinal transects, with high reclassification probabilities. (2) Allele and genotype frequencies at the α-Gpdh locus are strongly correlated with altitude, in sharp contrast to the presumable neutral markers. (3) Genetic differentiation is two to three times higher among populations across the tree line than among populations at or below. (4) Genetic differentiation between ecotypes within independent mountain areas is reflected by different sets of allozymes.

Screening for coeliac disease is recommended for children from certain risk groups, with implications for diagnostic procedures and dietetic management. The risk of a malignant complication in untreated coeliac disease is not considered high in children. We present the case of a girl with type I diabetes who developed weight loss, fatigue, and inguinal lymphadenopathy. Four years before, when she was asymptomatic, a screening coeliac tTG test was positive, but gluten was not eliminated from her diet. Based on clinical examination, a duodenal biopsy, and an inguinal lymph node biopsy were performed, which confirmed both coeliac disease and an anaplastic large-cell lymphoma. HLA-typing demonstrated that she was homozygous for HLA-DQ8, which is associated with higher risk for celiac disease, more severe gluten sensitivity, and diabetes susceptibility. She responded well to chemotherapy and has been in remission for over 4 years. She remains on a gluten-free diet. This is the first case reporting the association of coeliac disease, type I diabetes, and anaplastic large-cell lymphoma in childhood. The case highlights the malignancy risk in a genetically predisposed individual, and the possible role of a perpetuated immunologic response by prolonged gluten exposure.

Reports about superior mesenteric vein thrombosis in childhood are very rare and have not been associated with gastrointestinal bleeding. We describe two cases of severe bleeding from the upper and lower gastrointestinal tract in children who had undergone complex abdominal surgery at considerable time before. The first child had a tracheoesophageal fistula, corrected by division, gastrostomy insertion, and repair of duodenal rupture. The child presented with severe bleeding from the gastrostomy site and was diagnosed with a thrombosis of the proximal superior mesenteric vein. The second child had a gastroschisis and duodenal atresia, and required duodenoplasty, gastrostomy insertion, hemicolectomy, and adhesiolysis. The child presented with intermittent severe lower gastrointestinal bleeding, resulting from collateral vessels at location of the surgical connections. He was diagnosed with a thrombosis of the superior mesenteric vein. In both children, the extensive previous surgery and anastomosis were considered the cause of the mesenteric thrombosis. CT angiography confirmed the diagnosis in both cases, in addition to characteristic findings on endoscopy. Paediatricians should suspect this condition in children with severe gastrointestinal bleeding, particularly in children with previous, complex abdominal surgery.

The Agabus bipustulatus complex includes one of Europe's most widely distributed and common diving beetles. This complex, which is known for its large morphological variation, has a complex demographic and altitudinal variation in elytral reticulation. The various depth of the reticulation imprint, both in smaller and larger meshes, results in both mat and shiny individuals, as well as intermediate forms. The West Palearctic lowland is inhabited by a sexually dimorphic form, with shiny males and mat females. In mountain regions, shiny individuals of both sexes are found intermixed with mat individuals or in pure populations in central and southern areas, whereas pure populations of mat individuals are exclusively found in the northern region at high altitude. Sexual selection is proposed as a driving force in shaping this variation. However, the occurrence of different types of reticulation in both sexes and disjunct geographical distribution patterns suggest an additional function of the reticulation. Here we investigate the phylogeographical history, genetic structure and reticulation variation of several named forms within the Agabus bipustulatus complex including A. nevadensis. The molecular analyses recognised several well-supported clades within the complex. Several of the named forms had two or more independent origins. Few south European populations were uniform in reticulation patterns, and the males were found to display large variation. Reticulation diversity and population genetic variability were clearly correlated to altitude, but no genetic differences were detected among populations with mixed or homogenous forms. Observed reduction in secondary reticulation in female and increased variance in male at high altitude in South Europe may be explained by the occurrence of an additional selective force, beside sexual selection. The combined effect of these selective processes is here demonstrated in an extreme case to generate isolation barriers between populations at high altitudes. Here we discuss this selective force in relation to thermal selection.

The observation of place cells has suggested that the hippocampus plays a special role in encoding spatial information. However, place cell responses are modulated by several nonspatial variables and reported to be rather unstable. Here, we propose a memory model of the hippocampus that provides an interpretation of place cells consistent with these observations. We hypothesize that the hippocampus is a memory device that takes advantage of the correlations between sensory experiences to generate compressed representations of the episodes that are stored in memory. A simple neural network model that can efficiently compress information naturally produces place cells that are similar to those observed in experiments. It predicts that the activity of these cells is variable and that the fluctuations of the place fields encode information about the recent history of sensory experiences. Place cells may simply be a consequence of a memory compression process implemented in the hippocampus.