The principle of workplace based assessment (WBA) is to assess trainees at work with feedback integrated into the program simultaneously. A student driven WBA model was introduced and perception evaluation of this teaching method was done subsequently by taking feedback from the faculty as well as the postgraduate trainees (PGs) of a residency program.Descriptive multimethod study was conducted. A WBA program was designed for PGs in Chemical Pathology on Moodle and forms utilized were case-based discussion (CBD), direct observation of practical skills (DOPS) and evaluation of clinical events (ECE). Consented assessors and PGs were trained on WBA through a workshop. Pretest and posttest to assess PGs knowledge before and after WBA were conducted. Every time a WBA form was filled, perception of PGs and assessors towards WBA, time taken to conduct single WBA and feedback were recorded. Faculty and PGs qualitative feedback on perception of WBA was taken via interviews. WBA tools data and qualitative feedback were used to evaluate the acceptability and feasibility of the new tools.n = 7 and PGs n = 6), 12 ECEs (assessors n = 6 and PGs n = 5), and 20 DOPS (assessors n = 6 and PGs n = 6) were documented. PGs average pretest score was 55.6%, which was improved to 96.4% in posttest; p value< 0.05. Scores of annual assessment before and after implementation of WBA also showed significant improvement, p value 0.039, Overall mean time taken to evaluate PG’s was 12.6 ± 9.9 min and feedback time 9.2 ± 7.4 min. Mean WBA process satisfaction of assessors and PGs on Likert scale of 1 to 10 was 8 ± 1 and 8.3 ± 0.8 respectively.Six eligible PGs and seventeen assessors participated in this study. A total of 79 CBDs (assessors Both assessors and fellows were satisfied with introduction and implementation of WBA. It gave the fellows opportunity to interact with assessors more often and learn from their rich experience. Gain in knowledge of PGs was identified from the statistically significant improvement in PGs’ assessment scores after WBA implementation. Chemical pathology encompasses both practical laboratory and clinical skills. According to the guidelines of the College of Physicians and Surgeons of Pakistan (CPSP) 4 years’ training is required to satisfactorily complete the chemical pathology curriculum to the required depth and breadth. By the completion of training, the postgraduate (PG) trainees are expected to develop the desired competencies in the six major domains; medical expert, inter-professional communication, system based practice, professionalism, practice based learning and improvement and communication skills for independent practice. Interpretation and reporting is an important aspect of PG learning in chemical pathology –3. This A virtual learning environment (VLE) is a distance learning platform for synchronous or asynchronous teaching that integrates course materials, assignments, assessments, and other tools –15. For A descriptive multi methods study was conducted in the section of chemical pathology, Department of Pathology and Laboratory Medicine, Aga Khan University (AKU), Karachi, Pakistan. The study was conducted from January to December 2019 and was introduced in the training process of chemical pathology residency program. The chemical pathology training program is a 5 year residency at Aga Khan University; accredited by CPSP. The program is a self-directed adult learning, systemically organized in the form of week by week structured bench rotations for learning analytical skills and rotations for enhancing their clinical skills in practice of biochemical laboratory medicine to diagnose disease and to manage patients. The PG trainees must acquire a detailed understanding of biochemical processes and the changes that occur in various diseases while rotating through the benches/ subsections of chemical pathology which include the following: routine chemistries and enzymes; therapeutic drug monitoring and toxicology, immunoassays, biochemical genetics laboratory, urolithiasis laboratory service, point of care testing, electrophoresis and protein laboratory. A major part of fellows’ time is spent in advising other clinicians about the appropriate tests for the investigation of a particular clinical problem, the interpretation of results and follow-up, performing procedures, provocative tests and evaluating new tests for introduction in service, assay optimization and validation and research.Before initiating the study the university’s ethical review committee’s permission was sought. All PGs registered at CPSP, including fellows of chemical pathology training program at AKU and fellows rotating in section of chemical pathology from other pathology specialties from January to December 2019 were eligible to participate in the study. Faculty, senior technologists and managers at the section of chemical pathology were taken as assessors. Seventeen assessors and six eligible PGs were contacted for written informed consent and all agreed.To ensure that the outcomes achieved at the end of each phase meet their purpose, and that WBA program team members are properly prepared for the next phase we divided the WBA project into phases. To deliver the WBA program effectively the entire study process was divided into following seven phases:The chemical pathology residency program has a different teaching learning and training environment which includes report interpretations and correlating with clinical data, clinical audits, clinical consultations, and laboratory procedures, provocative testing, quality assurance measures and complaint handling. Therefore it was essential to know that the selected WBAs tools were fit for purpose. Using Norcini AMEE guide, validated WBA tools were chosen and modified according to the needs of chemical pathology residency program by WBA project team . These tThe process of WBA was clearly delineated with the goals of making it student driven and making it instrumental in the provision of feedback to PGs to navigate their learning towards desired outcomes. The PG was supposed to select a case (for CBD), any laboratory procedure (for DOPS) or complaint/ clinical audit (for ECE) which he/she has recently been involved with. The WBA process was to be initiated by PGs and they were supposed to select the assessor of their choice. For DOPS assessor was supposed to be present during the demonstration of the procedure by the PG. The discussion will start from and be centered on the PG’s record in the notes or reports and is designed to assess clinical decision-making and the application or use of medical knowledge in the care of patients. The discussion of assessors and PG would be followed by immediate feedback on assessment form uploaded on Moodle in another 5–10 min in the presence of the PG trainee. The assessments were to be performed against the standard expected at the end of the PG’s current stage of training and according to the level of complexity for each assessment. Guide for assessing complexity of cases, procedures or clinical events were prepared for the assessors. Low complexity WBAs were those that were uneventful and straight-forward with few demands made on the PG trainees, average complexity WBAs were those with manageable complications that most likely occur on a regular basis and high complexity WBAs were those that were difficult or unusual due to demanding encounters or unusual findings.The primary goal of the assessment was to provide relevant comprehensive feedback to the PGs. Prior to submitting any of the three WBA tools PGs and assessors’ satisfaction level with the overall WBA process was recorded on VLE. Satisfaction level of both PGs and assessors was gauged separately on a Likert scale of 1–10 every time a WBA tool was filled. To maximize the educational impact of WBA, assessors were invited to provide qualitative comments for PGs on their overall performance in CBD, DOPS or ECE.For WBA program structure, activities, management and application Moodle (free of charge resource) was selected as the VLE platform. With support from the department of I.T. Academic and Computing, the WBA tools finalized in phase I of the study were developed on the VLE and all essential documents including WBA process and assessors’ guide were uploaded Table . DescripA half day hands-on WBA workshop to prepare the assessors to use the VLE for WBA was designed and executed face to face to 15 participants. Thorough hands on training through this workshop of all assessors was done with added objective of controlling rater bias. In-depth briefing regarding the entire process of WBA was given by the principal investigator (PI) and CO-PIs through various activities to determine the strengths, weaknesses, opportunities and threats (SWOT) of introducing WBA, along with hands-on use of WBA tools  by role play. The SWOT analysis on WBA project was done in flipchart activity format with assessors by dividing them into four groups. Preliminary results from SWOT analysis were then detailed and the session invited comments and feedback using post-it’s to elaborate as described in Table A full hands-on workshop was conducted by experts from department of I.T. Academic and Computing to prepare the assessors to use the VLE for WBA seven master trainers. The workshop was a complete training session with hands on practice of using Moodle on individual laptops. Following the TOT methodology the master trainers, given the title of ‘Moodle Champs’, then trained the rest of the assessors in the Section by small group discussions. They demonstrated how to use VLE for WBA in multiple small group discussions.PG trainees were introduced to WBA with a presentation and eight to ten small group discussions on WBA and the use of VLE for teaching and learning. The whole WBA theory was explained and they were demonstrated the overall process of WBA. It was explained that it was for their benefit and to provide regular timely feedback to them. It was reiterated that in order to close the gap between actual performance and desired performance they need to actively take action and improve. Blueprint of the course curriculum was made available on VLE for them with the desired outcomes.Once WBA tools were developed, validated and tested on VLE, all assessors and PGs were trained and the process was clear to all participating the WBA process was implemented. Pretest of all PGs participating were conducted before WBA implementation and posttest was taken after 3 months of participating in WBA program. Being convenient, cost effective with the ability to cover broad content, multiple choice questions (MCQs) were chosen as the method of assessment for both pre and posttests. The MCQs based on CPSP chemical pathology residency program curriculum were developed by two content experts and uploaded on VLE. All 20 questions developed were scenario based and were structured for a higher cognition level of analyzing and interpretation. Data gathered during WBA execution were PGs performance through WBA tools, time spent in each WBA feedback and discussion and pretest and post test scores. Results of annual assessment before (year 2018) and after implementation (year 2019) of WBA were also evaluated to see the effect of WBA in PGs knowledge. Both type of assessments involved the same batch of PG trainees. The annual assessments of 2018 and 2019 were similar in content and structure using same table of specifications of chemical pathology course by paper setters. The assessments were blueprinted to the chemical pathology curriculum, ensuring that there was extensive assessment coverage of the curriculum content.Semi-structured individual interviews were conducted with randomly selected five assessors and PG trainees to gauge their response about the advantages of WBA, challenges faced and how they can be resolved. A quiet and convenient venue was chosen for the interviews. The interviews, which lasted 30 min to 1 h each, were conducted by one interviewer using a semi-structured interview format to promote a discussion and further questions. The interviewer, guided by the interview format, could direct questions in such a way as to facilitate more details and insight on the PG trainees’ and assessors’ responses. All questions were open ended. The main questions asked were as follows: how was their experience of using VLE for WBA and how could WBA program be improved? Data via interviews was being collected simultaneously from two sources; PG trainees and assessors. Data collection and analysis occur simultaneously so that the analyzed data guided subsequent data collection. The interviewer did not record the interviews but made written notes which were supplemented by extensions on those notes immediately following the end of the interview.P value < 0.05 was considered significant.All data from recorded WBA on VLE were extracted into excel spreadsheets. Mean ± SD were generated for quantitative data (pre and posttests scores). Pre and posttests score comparison and comparison of results of annual assessment and after implementation of WBA were done using paired sample t test. For qualitative data frequencies were calculated. The feedback interviews were conducted and analyzed using the constructive grounded theory approach . The notn = 7 and PGs n = 6), 12 ECEs (assessors n = 6 and PGs n = 5), and 20 DOPS (assessors n = 6 and PGs n = 6) were successfully recorded.Six eligible PGs and 17 assessors participated in this study. A total of 79 CBDs (assessors n = 79), 7 assessing components were marked ‘borderline’ while 2 components were found to be ‘below expectations’ at various events. PGs were at par in most of the discussions. Suggestions for development were provided in 49.3% (n = 39) of CBDs  recorded dealt with laboratory data interpretation followed by analytical  and preanalytical  issues. From the total cases in CBDs, 22.4% (n = 13) were of high complexity, 72.4% (n = 42) moderate and 5.2% (n = 3) of low complexity. Case mix included electrolyte imbalance, proteinuria, renal stones and renal failure, endocrinopathies , autoimmune disorders, hypervitaminosis D, dyslipidemia, liver and pancreatic insufficiency, sepsis, malignancies and rare diseases . The average time taken for CBDS’ discussion and feedback were 11.2 ± 5.3 min and 9.2 ± 7 min respectively. Out of the total CBDs conducted 41.7% (n = 33) got over within 20 min.The CBDs most frequently focused on clinical and laboratory data on an outpatient record  or inpatient record , and internal and external quality control summaries were also used. During the CBDs . Out of the total ECEs (n = 12) conducted, 50% (n = 6) were regarding consultation on laboratory data, 42% (n = 5) on complaint handling while no clinical audits were documented. All complaints or consultations discussed in ECE were of moderate complexity  to high complexity . Seven components of ECEs were marked ‘borderline’ at several times. Topics discussed in ECE were autoimmune disorders, anemia, malignancy, endocrinopathies, quality control and proficiency testing survey data and prenatal screening panel. Average time taken for discussion and feedback of ECEs were 8.7 ± 3.2 min and 7.7 ± 4.2 min respectively. Majority  of the time assessors and PGs got over with the discussion and feedback over within 20 min.The ECEs were most frequently conducted patients with outpatient record (n = 14) were on biochemical analysis and instrument handling while 30% (n = 6) were on procedural skills. Six components of DOPS were marked ‘borderline’ several times. None of these WBA demonstrated evidence of ‘below expectation’ by the assessors. Instruments on which DOPS was demonstrated were ion selective electrode analyzer, point of care testing, centrifuges, Fourier transformed infrared spectroscopy and biochemical methods discussed were stone analysis, arterial blood gases analysis, and protein electrophoresis. Additionally there were DOPS carried out on safety measures to be taken when there is a biological and chemical spill. Majority  of the time assessors and PGs got over with the observation of DOPS, discussion and feedback within 20 min.Out of the 20 recorded DOPS, 70%  indicates that WBA can be successfully integrated in a chemical pathology postgraduate training program. Further steps are to be taken to align WBA with the chemical pathology curriculum, EPAs and make the process acceptable at a national level. In short WBA implemented in chemical pathology had a catalytic effect creating more learning opportunities for the PG trainees and improving teaching and learning environment in the section.Additional file 1. Annexure 1 a. WBA form for Case-based discussion (CBD). b. WBA form for Direct observation of practical skills (DOPS). c. WBA form for Evaluation of clinical events (ECE).


Parent-child tie is important for parental later life due to insufficient old-age support in developing contexts. Parents often anticipate they would share the returns of children’s education for their early period investment. Previous studies show that adult children’s education is positively associated with parents’ survival and physical health in both low- and middle-income countries. What’s less discussed in literatures is the effect of adult children’s education on parental subjective wellbeing. Drawing the China Health and Retirement Longitudinal Study (CHARLS), this study intends to explore the effect of adult children’s education attainment on parents’ life satisfaction. This study uses information from baseline wave in 2011 and latest wave in 2015 of CHARLS. The analytic sample restricts to adult children aged between 25 and 49 with the highest education among all children of a parent who are aged between 50 and 84. To handle the reversed causality, this study adopts lagged effect model and controls for baseline subjective wellbeing. Instrumental variables (IV) are also used to handle the endogeneity issue existing between children’s education and parental wellbeing to conclude a causal effect. The preliminary results without IV reveal that association between children’s schooling years and parents’ life satisfaction is non-linear. However, results with IV show that adult children’s schooling years are negative associated with parents’ life satisfaction. This study firstly draws attention on negative sides of children’s education attainment on parental subjective wellbeing which implies more studies to unfold the mechanisms underlying the association.


Previous macrophysiological studies suggested that temperature‐driven color lightness and body size variations strongly influence biogeographical patterns in ectotherms. However, these trait–environment relationships scale to local assemblages and the extent to which they can be modified by dispersal remains largely unexplored. We test whether the predictions of the thermal melanism hypothesis and the Bergmann's rule hold for local assemblages. We also assess whether these trait–environment relationships are more important for species adapted to less stable (lentic) habitats, due to their greater dispersal propensity compared to those adapted to stable (lotic) habitats.We quantified the color lightness and body volume of 99 European dragon‐ and damselflies (Odonata) and combined these trait information with survey data for 518 local assemblages across Europe. Based on this continent‐wide yet spatially explicit dataset, we tested for effects temperature and precipitation on the color lightness and body volume of local assemblages and assessed differences in their relative importance and strength between lentic and lotic assemblages, while accounting for spatial and phylogenetic autocorrelation.The color lightness of assemblages of odonates increased, and body size decreased with increasing temperature. Trait–environment relationships in the average and phylogenetic predicted component were equally important for assemblages of both habitat types but were stronger in lentic assemblages when accounting for phylogenetic autocorrelation.Our results show that the mechanism underlying color lightness and body size variations scale to local assemblages, indicating their general importance. These mechanisms were of equal evolutionary significance for lentic and lotic species, but higher dispersal ability seems to enable lentic species to cope better with historical climatic changes. The documented differences between lentic and lotic assemblages also highlight the importance of integrating interactions of thermal adaptations with proxies of the dispersal ability of species into trait‐based models, for improving our understanding of climate‐driven biological responses. We quantified the color lightness and body volume of 99 European dragon‐ and damselflies (Odonata) and combined this trait information with survey data for 518 local assemblages across Europe to test whether trait‐environment relationships previously reported at coarse spatial scales also hold for spatially explicit local assemblages. We show that the color lightness of odonates assemblages increased and body size decrease with increasing temperature across Europe, supporting the thermal melanism hypothesis and Bergmann's rule, respectively. Accounting for differences in the dispersal/recolonization ability between lentic and lotic species and the phylogenetic relationships of species indicated that both groups show similar trait‐environment relationships in the phylogenetically predicted part of traits (evolutionary responses), but differ in their responses to (recent) historical climatic changes. Fundamental physical principles link both traits to the heat gain and loss of an organism  an increase in the color lightness of local assemblages of odonates with increasing temperature. If color lightness and body size are also involved in pathogen resistance and desiccation tolerance, we expect that (b) local assemblages of odonates are darker and smaller in more humid climates. In addition, given that adaptations to spatially and temporally less stable habitats allow lentic species to better cope with climatic changes , we predicted that (c) the slopes of these relationships would be stronger for lentic than for lotic assemblages.In this study, we investigated trait–environment relationships using spatially explicit survey data for local assemblages of dragon‐ and damselflies (Odonata) across Europe. Specifically, according to the thermal melanism hypothesis and Bergmann's rule sensu22.1Information on water body location and type  and the composition of local assemblages of odonates across Europe were compiled from data obtained in an extensive literature survey Appendix . Only re2.23 (π × [½ length of pixel row]2 × pixel edge length) as an estimate of the body size of a species based on the assumption that odonates generally have a cylindrical body form. The calculations were performed using functions of the R package png  was included as a predictor because of the protective function of melanin against pathogens under humid climates .ape  to facilitate their comparison. We checked mulitcollinearity among predictors, using the ar Table .ncf  of assemblages of odonates across Europe is mainly driven by temperature. In line with the predictions of the thermal melanism hypothesis and Bergman's rule sensu lato, we found that the average body size of assemblages of odonates decreased with increasing temperature. Even though a recent macroecological study by Zeuss et al. . Color‐ and size‐based thermoregulation was by far the dominant mechanisms shaping the composition of assemblages of odonates, although other functions of body size and color lightness seemed to influence the geographical patterns of both traits to some extent. The consistency of our findings together with the results of a number of macroecological analyses underlines the general importance of thermal melanism and Bergmann's rule for ectothermic organisms. However, besides highlighting the crucial role of traits involved in thermoregulation in shaping the distribution of odonate species, our results indicate that difference in species’ dispersal propensities embedded in the spatio‐temporal stability of their habitats contributes to explaining the scatter around the considered trait–environment relationships as well as to differences in the relative contributions of climatic predictors. Thus, thermal adaptations seem to be of similar evolutionary importance for lentic and lotic species but a greater dispersal ability of the former in combination with the climatic history of Europe seems to have allowed them better cope with historical climatic changes.The authors declare no conflict of interest.Daniel Acquah‐Lamptey: Conceptualization (lead); Data curation (lead); Formal analysis (lead); Methodology (lead); Writing‐original draft (lead); Writing‐review & editing . Martin Brändle: Conceptualization (supporting); Supervision (supporting); Writing‐review & editing . Roland Brandl: Conceptualization ; Methodology ; Supervision (lead); Writing‐review & editing . Stefan Pinkert: Conceptualization (lead); Data curation (lead); Formal analysis (lead); Methodology (lead); Supervision (supporting); Writing‐review & editing .Supplementary MaterialClick here for additional data file.


It is well established that GluA1 mediated synaptic plasticity plays a central role in the early development of AD. The complex cellular and molecular mechanisms that enable GluA1‐related synaptic regulation remain to fully understood. Particularly, understanding the mechanisms that disrupt GluA1 related synaptic plasticity is central to the development of disease‐modifying therapies which are sorely needed as the incidence of AD rises. We surmise that the published evidence establishes deficits in synaptic plasticity as a central factor of AD aetiology. We additionally highlight potential therapeutic strategies for the treatment of AD, and we delve into the roles of GluA1 in learning and memory. Particularly, we review the current understanding of the molecular interactions that confer the actions of this ubiquitous excitatory receptor subunit including post‐translational modification and accessory protein recruitment of the GluA1 subunit. These are proposed to regulate receptor trafficking, recycling, channel conductance and synaptic transmission and plasticity. GluA1 mediated synaptic plasticity plays a central role in the development of AD. Amyloid beta/Tau protein has been shown to impair GluA1 and cause synaptic dysfunction and acute neurotoxicity, respectively Deficits in synaptic plasticity, defined as any experience (activity)‐dependent changes that occur between neurons that alter their communication dynamics over time, have been a hallmark of the early aetiology of AD and similar age‐related cognitive disorders.At the memory epicentre, the hippocampus, AMPARs make up a large proportion of the excitatory synapse, up to 80% in the CA1 region.AMPAR subunits are highly susceptible to regulation through a myriad of PTMs conferring changes to protein interactions, each distinctly altering the properties and function of the receptor.In this review, we outlined the role of aberrant synaptic plasticity in the aetiology of AD (predominantly amyloid β‐driven and to a lesser extent tauopathy‐driven) and dived into the role of GluA1 in synaptic plasticity, in the hippocampus as it pertains to induction and maintenance of LTP and LTD , investigators demonstrated that AMPAR‐mediated (evoked and spontaneous) miniature currents are downscaled in an age‐related manner. Electron microscopy and immunohistochemistry confirmed the loss of AMPARs selectively at the CA1 stratum radiatum axo‐spinous synapses. Further, and functional tests further revealed the deficits in LTD/LTP and memory flexibility.Interestingly, emerging studies have elucidated a possible role for insulin resistance in the aetiology of AD and associated cognitive deficits.Progress in our understanding of the role of GluA1 and GluA1‐containing AMPARs in the brain will undoubtedly shed light on novel therapeutic strategies for the treatment of dementia and age‐related cognitive disorders like AD. For example, activation of M1 receptors promotes the membrane insertion of GluA1 through phosphorylation of S845, a critical site for AMPAR trafficking to the synapse.Hericium Erinaceus protected against di(2‐ethylhexyl)phthalate (DEHP)‐induced cell death. This hermetic action demonstrated both a stabilizing effect on mitochondrial membrane potential (due to reduction of intracellular ROS) and the activation of vitagenes regulated Nr2f.An emerging concept in Alzheimer's disease therapeutics is that sub‐toxic levels of endogenous and exogenous agents that induce oxidative stress may actually precondition the cell to future exposures such that beneficial pathways (maintenance and repair mechanisms) are triggered in response to the low‐threshold insult. In C. elegans, olive oil‐derived polyphenols demonstrated the ability to modulate stress response mechanisms to reduce the degradation of dopaminergic neurons.3α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid receptors mediate the majority of excitatory activity in the brain and are essential for learning and memory. AMPARs are highly mobile and undergo both constitutive and activity‐dependent trafficking to the synapse as well as recycling and degradation. Synapse function is dictated largely by the number, localization and subunit composition of AMPARs. GluA1‐containing AMPARs account for the majority of synaptic AMPARs in the hippocampus and are the only subunit capable of forming CP homotetramers.Additional evidence of the functional changes of GluA1‐containing receptors during synaptic plasticity is taken from GluA1 gene deletion studies in mice. One study found that GluA1 deletion generated impairments in spatial working memory though it enhanced spatial memory over a 24‐hr period (long‐term). These observations suggest that GluA1 plays a differential role in short‐term and long‐term memory.Much of AMPAR function is shaped by the subunit type availability at the synapse. GluA2‐containing AMPARs are continuously delivered to the spine in basal states. In contrast, GluA1‐containing AMPARs are enhanced in the synaptic surface following stimulation, first in the dendritic region followed by movement into the spines.It is widely accepted that LTP in the hippocampus requires an increase in AMPARs within the post‐synaptic density (PSD).During LTD, CP AMPARs (GluA1 homomers residing in the extrasynaptic region) are transiently recruited to the synapse via phosphorylation of GluA1 S845 by PKA.Like the aforementioned 4.1N, AMPAR trafficking is regulated by a myriad of accessory proteins, and deficits in the expression of these proteins lead to aberrant AMPAR trafficking and synaptic expression.While it has been hypothesized that age‐related deficits in AMPAR subunit trafficking and instability may reorganize the synaptic structure and underlie age and disease related changes in cognitive ability, little direct evidence is currently available. Similarly, it has been proposed that the presence of Aβ may increase AMPAR degradation, leading to synaptic decline. Particularly, the exogenous application of Aβ activates NMDARs and triggers the removal of AMPARs.4α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid receptors can arrive at the synapse by insertion into the plasma membrane followed by lateral diffusion to the synapse.Aβ induces synaptic aberrations by altering the morphology and composition of synapses that lead to significant dendritic spines loss.5Post‐translational modifications of the GluA1 subunit can alter the performance of the subunit‐containing receptor. This is achieved by altering the binding properties of the subunit, the recruitment of regulatory accessory proteins and complexes, and the overall probability of synaptic plasticity. One of the most common PTMs occurring in neurons is phosphorylation, which can regulate each of the four AMPAR subunits. Phosphorylation is critical for synaptic plasticity, with LTD induction generally associated with dephosphorylation of major PKA sites while LTP induction is associated with dephosphorylation of CaMKII sites.α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid receptors are susceptible to lysine acetylation at the C‐terminal, reducing AMPAR internalization and degradation, leading to increased cell surface localization and stabilization.Due to the influence of PTMs on AMPAR insertion, trafficking and stability, they have been investigated in the aetiology of AD. To date, one class of post‐translational modification has stood out in the body of AD research. AMPAR ubiquitination and subsequent removal of AMPARs from the plasma membrane has been demonstrated in cultured neurons exposed to soluble Aβ oligomers. This exposure produced reductions in AMPAR currents as well as spine loss.6GluA1 properties are heavily regulated by synaptic protein interactions. For example, the cytoskeletal protein Arc acts as an immediate early gene that can be induced in the nucleus in response to excitatory activity.Pathologically, Aβ has been shown to alter the synaptic distribution of the kinase CaMKII. For instance, in APP transgenic mice, the pool of CaMKII is reduced and in cortical neurons treated with Aβ oligomer, decreased CaMKII clusters are present at the synapse.7In the United States alone, AD impacts over 5 million and is estimated to bear a 200 billion dollar per year economic burden. The disease is particularly pressing as society faces an increased ageing population. Thus, elucidating the underlying mechanisms of cognitive and memory function and decline is especially important. An increasing body of evidence has implicated Aβ and tau aggregates to a host of deleterious neurobiological processes such as reductions in excitatory synaptic transmission, loss of dendritic spines and excitotoxic neuronal death. Indeed, a hallmark of AD aetiology includes dysregulated synaptic transmission that has been largely attributed to dendritic spine loss, deficits in glutamatergic synaptic transmission and impaired cognition, learning and memory capacity. Interestingly, these phenomena have been found to occur prior to the detection of pathological plaques and neuronal loss. This beckons the question of whether any of the above described molecular pathologies are consequence or cause. Regardless, the evidence is quite clear in that AD affected subjects distinctly suffer inhibited LTP due to reductions in excitatory neurotransmission. As a major excitatory receptor in the central nervous system, AMPARs have been a focus of AD research. Indeed, as previously discussed, AMPAR abundance, trafficking, localization and function have all been shown to be dysregulated across various AD models. The receptor subunit GluA1 is perhaps the most well‐studied component among AMPARs. Through a variety of molecular mechanisms including trafficking, recycling, modifications of microstructural properties, PTMs and modulations due to interactions with critical synaptic proteins, GluA1‐containing AMPARs are a medium for the aetiology of AD and similar neurogenerative pathologies.In this review, we discussed various aspects of GluA1’s role in establishing synaptic plasticity, a fundamental component of cognitive processes like learning and memory. Specifically, we highlighted peer‐reviewed findings in the areas of GluA1 trafficking to and from the synapse, microstructural adaptations caused by GluA1‐containing receptor modulation, single‐channel functional modulation and well‐studied PTMs that influence interaction of the subunit with regulatory proteins. Altogether, these variations provide ample possibilities for GluA1‐containing AMPARs to modify synaptic transmission to shape LTD/LTP and subsequently learning and memory. Many questions stand including the resolution of a complex network of subunit diversity, PTMs and regulatory protein interactions. Additionally, potential crosstalk between PTM‐conferring proteins, compensatory mechanisms and feedback loops remain to be fully characterized. Undoubtedly, the list of proteins able to regulate synaptic AMPAR levels and their activity remains incomplete. Further, it is likely that live, high‐resolution microscopy has only begun to reveal the intricacies of molecular movement at the synapse. Finally, pathology‐driven changes in GluA1 dynamics and novel therapeutic strategies to address these remain to undergo a battery of clinical investigation.The authors declare that they have no competing interests.WQ, BY and QL conceptualized and design the manuscript. WQ, JL, RC and XZ searched the literature and wrote the manuscript. WY and BL viewed, edited and approved the manuscript. All authors read and approved the final manuscript.


Participants in both conditions completed surveys at baseline and 1‐week posttraining. Mixed‐factorial analysis of variances revealed a significantly higher decrease in JPOs' punitive attitudes from pre‐ to posttest, in the training condition compared to the control group, with a medium effect size. Rehabilitative attitudes decreased in both conditions, while recidivism risk perceptions did not change from pre‐ to posttest in either condition. Future research could expand on these promising results using a more intensive training program and a randomized‐controlled design in a larger sample of JPOs.The present quasi‐experimental study examined the impact of a brief training program based on the risk–need–responsivity (RNR) model on Turkish juvenile probation officers' (JPOs) punitive and rehabilitative attitudes toward justice‐involved youth and recidivism risk perceptions. Fifty‐nine JPOs were recruited through three probation offices in Istanbul, Turkey. Thirty‐six JPOs, who received a 1‐day training in the RNR model of offending behavior, were compared to JPOs in a wait‐list control condition ( Youth uGiven that the probation system is relatively new in Turkey, there is a lack of research on youth recidivism rates as well as antecedents to youth justice involvement. In other countries, including the US and European countries, a wide array of research has been conducted to identify the risk factors for reoffending. Moffitt  has propSeveral studies focused on the implementation of intervention programs for youth in probation and have widely documented the ineffectiveness of punishment‐oriented approaches in reducing youth recidivism Lipsey, . In a meThe Turkish probation system currently lacks an evidence‐based intervention and training framework, and the current study is a first step to address this need. In an attempt to introduce a rehabilitation‐oriented probationary supervision approach for Turkish youth under probation, we designed a 1‐day RNR‐based training to initiate an attitudinal change in JPOs. It was especially important to target the JPOs and engage them in a training program because they serve as active agents of change and their values and attitudes contribute to the goal of the probation system Werth, . It has The current study examined the effect of brief RNR training on JPO's attitudes and recidivism risk perceptions. We hypothesized that the difference between pretest and posttest scores on attitudes and recidivism perceptions would be significantly higher in the RNR training group than the control group. That is, JPOs in the intervention condition would show significantly less punitive attitudes, more rehabilitative attitudes, and lower recidivism risk perceptions from pre‐ to posttest than those in the control condition.22.1This study was designed as a pilot study , serving both adults and youth under probation. They were comparable in terms of staff numbers and size .1Participants who confirmed their availability to complete both assessments and the training were recruited for the study because there was significant mobility of POs across sites and cities at the time of data collection. Eligible JPOs willing to participate in the study were recruited upon providing written informed consent. To ensure voluntary participation, supervisors were not involved in the recruitment process. Besides, the participants were informed about their right to skip survey questions and to withdraw from the study at any time.Participation in the research project and the training was voluntary. To be eligible, participants had to be currently working with at least one youth under probation and be committed to complete both assessments at pretest and posttest.n = 96) were invited to the study and 59 officers agreed to participate (participation rate: 64.1%). The most common reasons for not participating were annual or maternity leave, having to attend another training, and a high workload. The total sample included 59 JPOs with 22 participants from Office 1 (training condition), 14 participants from Office 2 (training condition), and 23 participants from Office 3 (control condition).The study employed a quasi‐experimental pretest posttest intervention design with a wait‐list (no‐training) control group. All JPOs across three sites  and had a college degree . The average age was 31.31 years . Participants reported 5.9 years  of work experience in the criminal justice system on average. The two conditions did not differ in terms of gender, age, and years of work experience in the probation system. All participants in the training condition attended all RNR modules (100% attendance rate) and completed the surveys. All participants in the control condition completed the pretest while three of the 23 participants missed the posttest survey (13% attrition rate).The demographic characteristics of the sample are available in Table 2.3Upon obtainment of written informed consent, participants continued with the pretest assessment. The survey included a demographic questionnaire, scales that assessed attitudes toward justice‐involved youth, and JPOs' perceptions of the likelihood of recidivism. Participants in both conditions spent approximately 10 min completing the survey. After the initial assessment, the JPOs in the training condition received the 1‐day RNR‐based training while those in the control condition were wait listed. Both groups completed the posttest survey 1 week after the pretest. Participants in the control condition received the RNR‐based training after the study was completed. The Turkish Ministry approved the present study with protocol number 46985942/151/18410. Ethical approval was obtained from the Institutional Review Board (IRB) of Koç University with protocol number 2017.009.IRB3.005.2.4The principles of the training conformed with Bonta's et al.  and VincThe first module comprised a review of the rationale for the training and an introduction to empirical research on rehabilitative versus punitive approaches to probation. The focus of the first module was to challenge common misconceptions  about justice‐involved youth by presenting findings from current research on youth delinquent behavior. In addition, the JPOs were informed about findings on the criminal trajectories and reoffending risk of justice‐involved youth  to 5 (strongly agree) to measure punitiveness toward justice‐involved youth, derived from Vincent et al.  to 5 (strongly agree) was used , and χ2 tests were conducted for categorical variables  to examine group differences at baseline. For the main analysis, this study goal was to examine the amount of change in punitive attitudes, rehabilitative attitudes, and recidivism risk perception from pre‐ to posttest as a function of intervention condition. Therefore, we ran a mixed‐factorial analysis of variance (ANOVAs) for each dependent variable with time (pretest vs. posttest) as a within‐subjects factor and group (intervention vs. control) as a between‐subjects factor. The analysis examined the main effects of time (pretest and posttest), main effects of condition (intervention vs. control), and interaction effects (time × condition). The interaction effects on the dependent variables were the main analyses of interest, because we expected a higher impact of the intervention condition, as compared to the control condition. Cohen's d was calculated as a measure of effect size.Initial analyses focused on the comparison of demographic characteristics and outcomes of training and control groups at baseline, to examine the compatibility of the two groups. Independent samples 33.1χ2 (1) = 2.24, p = .13], age , years of work experience , or size of caseload . An exception was education level; a higher proportion of participants in the control condition had a graduate degree, compared to those in the training group , rehabilitative attitudes , or recidivism perception at baseline . Therefore, educational level was not included in subsequent analyses as a control variable. Independent samples t tests revealed no significant differences between training and control groups in punitive attitudes , rehabilitative attitudes , and recidivism risk perceptions  at pretest.The demographic characteristics of the training and control groups were compared at pretest  = 2.35, p = .13] nor for the condition  on punitive attitudes. We found a significant interaction effect on punitiveness , revealing that JPOs in the training condition reported a significantly larger decrease in punitive attitudes than JPOs in the control condition.We present mixed‐factorial ANOVA results in Table 3.2.2F  = 4.41, p = .04], but not condition , indicating that rehabilitative attitudes significantly decreased in both groups, but the decrease was not significantly different between training and control conditions. There was no significant interaction effect for rehabilitative attitudes .Regarding rehabilitative attitudes, we found a significant main effect of time , nor the main effect of the condition  or interaction effect  for recidivism risk perception. Figure There was no main effect of time [F , 54 = 1.4The training was based on the RNR framework that offers a rehabilitative approach to supervision and was implemented in the primarily punitively oriented criminal justice system of Turkey with the second‐highest incarceration rate in Europe  found that officers struggled to implement a rehabilitative approach within the probation service due to barriers in coordination with other governmental agencies in referrals and limited availability of learning and rehabilitative programs for justice‐involved youth  and randomization, with longer term follow‐up postintervention.The findings of the current study should be interpreted with caution due to several limitations. The current study implemented a pre‐post test wait‐list control group design with a small sample size. The current study is underpowered, given that the minimum sample size to achieve 0.80 power at  and Tan . However and Tan . Given tAnother limitation was the low internal reliability of the support for rehabilitation scale, indicating potential measurement error in assessment. Additionally, the absence of actual recidivism data of justice‐involved youth is a significant issue in the current study. We used outcome measures focused on change in JPOs' attitudes and recidivism risk perceptions only, rather than a change in behavioral outcomes of the justice‐involved youth. Additionally, the JPOs in the Turkish criminal justice system have high mobility , limiting the opportunity to conduct long‐term follow‐up assessments. Thus, the current design does not examine the long‐term sustainability of program effects on punitive attitudes.4.2Overall, the findings of the current study suggest that the interplay between punitive versus rehabilitative attitudes towards justice‐involved youth is complex. It appears that punitive and rehabilitative approaches may not necessarily be mutually exclusive in the Turkish context because they may not be opposite ends of the same spectrum. That is, training that reduces punitive attitudes may not promote rehabilitative attitudes to the same extent. Prior research has also shown that POs may integrate rehabilitative and punitive attitudes in their supervision practices at varying levels Miller, . Still, Furthermore, it was unexpected that rehabilitative attitudes decreased among the JPOs in both conditions. This finding may be pointing at a measurement problem. Thus, it calls for more research on how best to measure rehabilitative attitudes and endeavors for the development of more precise measures.The current study has implications for youth probation practices in Turkey. The RNR‐based training was tailored to meet the needs of Turkish JPOs and materials are available for the JPOs to execute a more collaborative approach in their work with youth on probation. Our project also sparked the interest of UNICEF Turkey and the Turkish Ministry of Justice to expand and implement an RNR‐based approach in the youth probation system. In 2018, we launched a large‐scale country‐wide project to develop an RNR‐informed risk assessment protocol and a new rehabilitation system targeting 12‐ to 18‐year old youth on probation. The program is currently implemented in 24 probation offices across 21 cities in Turkey .5This study was the first to implement and evaluate RNR‐based training in the Turkish youth probation system. With limited means, we managed to demonstrate that Turkish JPOs' punitive attitudes could decrease via brief intervention. Future studies should explore the long‐term impact of RNR‐based training on JPO's attitudes, their real‐world interactions with justice‐involved youth, and the possible impact on recidivism reduction.


Oncorhynchus tshawytscha), a region of major effect for migration timing has been discovered that harbors two adjacent candidate genes , but there has been limited work to examine the association between these genes and migratory phenotypes at the individual, compared to the population, level. To provide a more thorough test of individual phenotypic association within lineages of Chinook Salmon, 33 candidate markers were developed across a 220 Kb region on chromosome 28 previously associated with migration timing. Candidate and neutral markers were genotyped in individuals from representative collections that exhibit phenotypic variation in timing of arrival to spawning grounds from each of three lineages of Chinook Salmon. Association tests confirmed the majority of markers on chromosome 28 were significantly associated with arrival timing and the strongest association was consistently observed for markers within the rock1 gene and the intergenic region between greb1L and rock1. Candidate markers alone explained a wide range of phenotypic variation for Lower Columbia and Interior ocean‐type lineages , but less for the Interior stream‐type lineage (5%). Individuals that were heterozygous at markers within or upstream of rock1 had phenotypes that suggested a pattern of dominant inheritance for early arrival across populations. Finally, previously published fitness estimates from the Interior stream‐type lineage enabled tests of association with arrival timing and two candidate markers, which revealed that fish with homozygous mature genotypes had slightly higher fitness than fish with premature genotypes, while heterozygous fish were intermediate. Overall, these results provide additional information for individual‐level genetic variation associated with arrival timing that may assist with conservation management of this species.Recent studies have begun to elucidate the genetic basis for phenotypic traits in salmonid species, but many questions remain before these candidate genes can be directly incorporated into conservation management. In Chinook Salmon ( We used the program Haploview v4.2 to visualize haplotype blocks independently for each population  and selectively neutral set of SNPs that could be used as a covariate for population structure and relatedness in further analyses, we used a previously published panel of 298 SNP markers and a single sex marker from the Chinook sdY region  function implemented in the GAPIT R package, which allows for the inclusion of fixed and random effects to account for population structure and relatedness, respectively  as implemented in the GAPIT R package to test the effect of multiple markers simultaneously .To determine whether there was an association between fitness and candidate markers on chromosome 28, we used a subset of data that were available from Johnson Creek that included reproductive success . It is important to point out, however, that there are limitations of using R2 values to explain the percent of variation in models with binary response variables . Therefore, we also include results from a genomic relatedness‐matrix restricted maximum likelihood (GREML) method implemented in the genome‐wide complex trait analysis (GCTA) software to estimate the variance in arrival timing explained by genetic variance  for the Interior stream‐type population and also added year as a fixed effect. Power calculations using the GCTA‐GREML power calculator indicated <10% power to estimate VG/VP with high accuracy  and 2011 . Models were run separately for each sex and with sexes combined. The best fit model for sexes combined, males, and females included predictors of quadratic arrival time, sex, year, age, and one (out of two) of the candidate markers on chromosome 28 , supporting previous studies identifying this candidate region of the genome  and in selection for the trait in certain years compared to others . Previous research has shown that ocean and stream conditions directly affect migration timing (Anderson & Beer, Across all three populations, there was evidence that heterozygotes at the most significant candidate markers demonstrated early arrival timing which provides information regarding the mode of inheritance patterns beyond previous studies (Prince et al., While balancing selection may maintain phenotypic variation for both early and late migration phenotypes through disruptive selection related to high stream temperatures in the middle of migration (Narum et al., As suggested by Waples and Lindley , gainingNone declared.Supporting informationClick here for additional data file.


Cholangiocarcinoma is a type of malignant tumor derived from the epithelium of the bile duct. Cases of cholangiocarcinoma metastasis to the lung are rare, especially those with imaging features of multiple cavities in bilateral lungs. Here, we report a case of a patient who had previously undergone radical resection of primary distal cholangiocarcinoma 18 months ago. Transbronchoscopic lung biopsy of the right lung and biopsy of the left supraclavicular lymph node were performed for pathology confirmation, as well as immunohistochemistry. Multiple cavity shadows in bilateral lungs and enlarged lymph nodes were found on the computed tomography (CT) scan obtained 18 months postoperatively. No obviously enlarged lymph nodes were observed under the carina and beside the aortic arch, whereas enlarged lymph nodes were found above the left clavicle. Biopsy of lung and supraclavicular lymph nodes confirmed metastatic adenocarcinoma. Immunohistochemistry showed that it originated from the digestive tract and had the same homology as cholangiocarcinoma . Cholangiocarcinoma can be transferred to the lung and the left supraclavicular lymph nodes through the lymphatic pathway by characteristic jumping lymph node metastases. Diffuse cystic change is a specific CT manifestation of the lymphatic lung metastasis of cholangiocarcinoma. cystic cavity‐characteristic CT signs of translymphatic pulmonary metastasis in cholangiocarcinom. Cholangiocarcinoma is a type of malignant tumor derived from the epithelium of the bile duct. Radical surgical resection is the only effective approach for treatment. However, cholangiocarcinoma can easily relapse after surgical resection, with a three‐year survival rate after surgery within 40%–60%,The patient was a 69‐year‐old woman of Han nationality. She was admitted to the Hospital with coughing that had lasted for two months which had been aggravated by fever for three days. She had a previous history of right breast cancer resection 16 years ago, with no history of smoking. She had a history of modified radical thyroidectomy for left thyroid cancer with partial thyroidectomy for right thyroid lobe for five years, and continuous oral administration of Euthyrox. Choledochectomy, pancreatectomy, and subtotal gastrectomy had previously been performed 15 months ago. Postoperative pathology examination showed moderately differentiated adenocarcinoma in the lower segment of the common bile duct and the ampulla of the duodenum Fig . ImmunohThe lower segment of cholangiocarcinoma is prone to vascular infiltration and early lymph node metastasis because it is surrounded by the portal vein, superior mesenteric artery and vein, and lymphatic vessels. The prognosis of this malignant tumor is closely related to the presence of lymph node metastasisCavitary pulmonary metastasis often accompanies squamous cell carcinoma of the head, neck, and cervix, as well as gastrointestinal tract adenocarcinoma, gallbladder cancer, bladder cancer, and ovarian adenocarcinoma and osteosarcoma.The authors of this work have nothing to disclose.Figure S1. Immunohistochemical staining of Villin in bile duct, supraclavicular lymph node and lung tissue. (a) Cholangiocarcinoma, immunohistochemical staining showed positive Villin and Tan under a microscope (10 × 10); (b) Immunohistochemical staining of supraclavicular lymph node showed Villin‐ and Tan‐positive results under a microscope (20 × 10); (c) Immunohistochemical staining of lung tissue showed Villin‐ and Tan‐positive results under a microscope (20 × 10).Click here for additional data file.


Agrotis infusa is well known for its remarkable long‐distance migration – a return journey from the plains of southeast Australia to the Australian Alps – as well as for its cultural significance for Indigenous Australians. Each spring, as many as four billion moths are estimated to arrive in the Australian Alps to aestivate in cool mountain caves and in boulder fields, bringing with them a massive annual influx of energy and nutrients critical for the health of the alpine ecosystem. However, a massive decline in moths present at their aestivation sites has occurred over the past 3 years, with only a few individuals present where hundreds of thousands could earlier be found. In order to understand the possible sources of decline, we analysed historical records of Bogong moth numbers at aestivation sites in the Australian Alps, including observations on Mt. Gingera (NSW) in the early 1950s, observations from 1980 onwards in the Snowy Mountains (NSW) and an almost‐unbroken series of observations each summer over the past 53 years in three caves at different elevations on Mt. Buffalo (Victoria). This analysis shows that moth numbers were probably steady from 1951 until about 1980, fluctuated and slowly fell from then until 2016 and dramatically crashed in 2017. In the Murray–Darling Basin, the main winter breeding ground of Bogong moths, changes in farming practices, such as increasing land clearing for crops , has probably driven some of the decline in Bogong moth numbers observed from 1980 to 2016. The impact of insecticide remains unclear and is in urgent need of further study. Even though we found little evidence that increasing global temperatures per se are responsible for the Bogong moth decline, the Australian climate has nonetheless become drier and warmer over past decades, possibly hampering the survival of immature stages in the breeding areas and confining adult aestivation to gradually higher elevations. The crash in moth numbers from 2017 is most likely due to the recent severe drought in the moth's breeding grounds.The Bogong moth  Agrotis infusa is well known for its remarkable long‐distance migration  and NSW, and in the Bogong Peaks and Snowy Mountains of NSW, and at a number of granitic sites in Victoria, including Mt. Buffalo and the Jaithmathangs. These mountains are characterised by granitic outcrops and boulder fields Common  and inclThe first 30 years of Bogong moth research (1950–1980) established the numbers of Bogong moths at a time when climate change was becoming an issue of concern, with the global mean surface temperature having now been established relative to the 1951–1980 mean (ASA Goddard Institute for Space Studies). In 60 years of recorded measurements from the central Snowy Mountains, there has been a steady decrease in the maximum depth of the snowpack, and a shortening of the mean duration of the snowpack, by 18.5 days. These changes have resulted from a mean temperature increase of 0.36°C per decade  giving a total of around 7.9 billion larvae within the region of grey cracking clays of NSW and Queensland. Adult Bogong moth numbers were also calculated for the Snowy Mountains, based on calculations of predation and other sources of mortality , no evidence of Bogong moth aestivation was found in the bat‐free caves around the summit (at 1510 m). However, some of these caves housed other species of moths, such as the Granny's Cloak moth et al. As part of studies of the Bogong moth migration, adult moths were collected at light traps during spring on Mt. Kaputar in northern NSW. These moths were flying south‐southwest .et al. et al. As Bogong moths arrive in the vicinity of the caves in the Australian Alps, they first arrive at lower elevations where they shelter and feed until conditions improve sufficiently at higher elevations to ascend to their aestivation caves , Caley and Welvaert  found thWhen the Bogong moths arrive at these lower elevations, it is likely that snow still blocks the entrances to their aestivation caves at higher elevations. However, Bogong moths can shelter at higher sites without snow blockage, even where sub‐zero temperatures have been recorded using temperature loggers . Most moths, however, are likely to be elsewhere, feeding or waiting at lower elevations to move up hill to the aestivation sites. The lack of suitable sites at these elevations makes it difficult to obtain data on these locations. However, predators such as mountain pygmy possums and foxes provide a suitable source of data. The diet of foxes was studied along a transect from 1500–1800 m elevation at Schlink Pass in the Kosciuszko National Park  by ski surveys occurring on an almost daily basis from August until October since 1979 Fig. . The earWhen conditions become less favourable at lower elevations, for instance due to rising temperatures, Bogong moths ascend to their aestivation caves in the alpine zone above the tree‐line. Temperature is probably a major factor setting the lowest elevation where aestivation is possible, and this is likely to be related to summer temperatures within the caves, although significant variation in this temperature occurs depending on the location Table .Qualitative observations of Bogong moth numbers at four main locations in the Australian Alps have been made continuously or sporadically by a number of individuals (including the authors) over the past 70 years Table . A numbe3: Mansergh and Heinze Mt. Gingera is the site where Ian Common first described the aestivation and natural history of Bogong moths in the early 1950s Common . Common'Long‐term records of Bogong moth numbers from caves on Mt. Buffalo 1600–1723 m) in Victoria (started in the mid‐1960s) and caves at different elevations at Ken Green Bogong (1860–2020 m) in the Kosciuszko Main Range of NSW (started in the mid‐1970s), also reveal interesting trends . At the summit of Ken Green Bogong, which was visited on 10 January and 5 February 2018, the walls of the main cave were empty, with moths only found in deep crevices. This was the lowest number of Bogong moths ever recorded for this location (KG), with a similar report from Mount Buffalo for 18 and 19 January 2018 (MB).During the following summer season of 2018–2019, Mt. Buffalo was investigated on 16 December 2018, and no moths were found (KG). The following day, moths were observed in three deep locations of the major upper cave on Ken Green Bogong (2020 m). Three other caves at lower elevations near Ken Green Bogong were empty, apart from three moths inside one cave (KG). At the same time on Mt. Gingera, very few moths were observed Fig. . On 7 JaDuring the spring of 2019, unexpectedly high numbers of Bogong moths flew into the Snowy Mountains and the Victorian Alps, despite little relief in the drought. Why or how this was possible is not clear. There were localised heavy falls of rainfall in areas of southwest Queensland from February to April 2019, leading to flooding in some areas of southern Queensland that extended into northern NSW. These weather patterns also led to reasonable falls in localised areas of western NSW that may have promoted Bogong moth reproduction and survival. However, no matter what the cause, the increased numbers of moths entering the mountains during the spring of 2019 translated into considerably larger aestivating cave populations than seen in the previous two summers (but nowhere near as high as before the drought), although apparently only at higher elevations. On Mt. Gingera Fig. , a lowerOur results, taken together with observations by Ian Common in the early 1950s, suggest that the Bogong moth population was stable until the early 1980s but since then has fluctuated, and on average slowly declined, until crashing over the last 2–3 years. This rapid decline has probably had a deleterious impact on the health of the alpine ecosystems of south‐eastern Australia which depend on the massive influx of energy and nutrients that Bogong moths provide via their summer migration to the mountains , or as a result of curiosity and interest . In the past, few could have predicted that Bogong moths, usually common and plentiful in the Australian Alps, could now become so threatened, thus motivating the type of extensive population monitoring that would have strengthened the conclusions of this review (and which are likely warranted in the future). Thus, our data only represent a handful of aestivation sites – fewer than 70 – although these are spread across their full latitudinal range and at a number of elevations. But this admittedly fragmented data – complemented by analyses of the faeces of Bogong moth predators – show that Bogong moth numbers are worryingly in decline.et al. There are several possible causes of this decline, including agricultural practices (e.g. habitat loss and insecticides), climate change (particularly drought) and other factors . These factors have been implicated in the recent dramatic declines of insects across the globe, both in terms of population loss and species extinctions . If, after 1980, farming practices gradually reduced the number of Bogong moths in the breeding areas over the following 35 years, it is still difficult to disentangle agricultural impacts (e.g. habitat loss and pesticide use) from impacts arising from the increasing temperatures that have resulted from climate change.To address the possible impacts of pesticides, Bogong moths were collected in 2001 from a cave at Ken Green Bogong (1940 m) and were analysed by the NSW Department of Agriculture for sublethal levels of 59 chemicals currently used in agriculture. These analyses revealed no traces of these agricultural chemicals. Bogong moths killed by spraying in Parliament House in Canberra were collected in spring 2003 and were analysed for 139 different chemicals by the Australian Environmental Protection Authority. The pesticide used – Deltamethrin (USEPA/OPP Pesticide Code: 097805) – was recorded at a rate of 0.95 mg/kg. Deltamethrin is a pyrethroid ester insecticide and the main constituent of Cislin 10, one of the most popular insecticides in the world. Apart from Deltamethrin; the moths collected at Parliament House contained only trace concentrations of other pesticides . On average, the annual production area of rice is between 65 000–90 000 ha , can be explained by either of two possible  scenarios: (1) lower elevation aestivation sites are becoming less suitable due to climate change or (2) higher elevation aestivation sites have always been preferred by the moths, but when high numbers of moths filled the higher sites, additional moths were forced to aestivate at the lower (and less‐preferred) sites, so that when moth numbers began to decline, these lower sites emptied first.Both of these scenarios are supported by the long‐term moth declines observed at lower elevations in the Australian Alps. The lower cave on Ken Green Bogong has almost always had a high number of moths in early spring–summer, but numbers decline to zero in mid‐summer as moths move higher. This situation could well have been mirrored on Mt. Gingera during the summers of 2014–2015, 2015–2016 and 2019–2020 when Bogong moth numbers first rose and then declined  be? The lowest definitely known and regularly frequented whole‐summer aestivation elevation is 1600 m at Mt. Buffalo – equivalent to 1700 m at Mt. Gingera when one accounts for Mt. Buffalo's 1.15° more southerly latitude. This is only slightly lower than the lowest known aestivation sites below the summit of Mt. Gingera  and Victoria . What do these elevations suggest about the maximum permissible aestivation temperature? Data given in Table From the turn of this century, Bogong moths at aestivation sites on Mt. Gingera have declined during a 0.7°C temperature increase  was particularly severe and badly affected the Murray‐Darling Basin and virtually all of the southern cropping zones . Bogong moths continued to be found at lower levels on Mt. Buffalo but the drought had major impacts on moth numbers in the Snowy Mountains during the summers of 2006–2007 and 2008–2009 Table . Howeveret al. In addition to agricultural practices and climate change, annual declines of Bogong moth numbers may have occurred for the following reasons: (1) attrition as larvae in soil that is too dry and/or too warm (as likely occurred during winter 2017 and 2018), or attrition during adult migration as a result of (2) introduced predators, (3) environmental factors (such as increasing light pollution) or (4) because of attrition once the moths reach the mountains . Obtaining a measure of the numbers of moths existing as larvae Green , or as aTen years ago, a total number of 2.2 billion aestivating Bogong moths was estimated to exist in the Snowy Mountains over the summer Green . This nuRecords of Bogong moths collected over the past 70 years from around 50 to 60 aestivation sites, and more recently along the migratory route, coupled with the analysis of Bogong moth remains in mammalian predator faeces, reveal noticeable patterns in the numbers of moths present over summer in the Australian Alps. Even though the data (our own and those of others) are admittedly fragmentary, this analysis has revealed that Bogong moth numbers were fairly stable from 1950 until around 1980, apart from temporary falls in numbers due to occasional drought. From 1980 until 2016, Bogong moth numbers in the mountains began to fluctuate, with some years having very high numbers of moths, while others had many fewer. Even though overall numbers remained high, these years showed evidence of a slow decline. From 2017 to 2020 a sudden and worrying crash in Bogong moth numbers occurred.per se are responsible for the decline in Bogong moths seen across the mountains; however, the Australian climate has nonetheless become continuously drier and warmer over past decades. This change in climate has possibly had a serious impact on the ability of Bogong moth eggs, larvae and pupae to survive the winter in their breeding grounds, which in turn may have slowly been reducing the number of moths entering the mountains. Moreover, our analysis also suggests that the maximum temperature for aestivation may be around 16°C, and that a warming climate is thus likely restricting aestivation to higher and higher elevations. These possible effects of climate change, added to known changes in farming practices, such as increasing land clearing for crops and an elevated use of insecticides, may account for the gradual decline in moth numbers observed from about 1980 until 2016. These declines were followed by the catastrophic Bogong moth summers of 2017–2018 and 2018–2019 (and to a lesser extent 2019–2020) for which only drought can be seen as the cause. This drought is very likely to have severely impacted the survival of Bogong moth immature stages in their breeding grounds, a speculation supported by the sudden disappearance of Bogong moths that we observed along their migratory routes during Spring. The latest drought – the worst in recorded history in the Murray–Darling Basin – is almost certainly the result of climate change , places it on‐par with its better‐known diurnal counterpart in North America, the Monarch butterfly Danaus plexippus (Reppert and de Roode et al. The Bogong moth is an iconic and culturally significant Australian insect whose remarkable highly directed migration (Warrant


An apparent increased interest has been recently devoted towards the previously untrodden path for anionic point defect engineering of electrocatalytic surfaces. The role of vacancy engineering in improving photo‐ and electrocatalytic activities of transition metal oxides (TMOs) has been widely reported. In particular, oxygen vacancy modulation on electrocatalysts of cobalt‐based TMOs has seen a fresh spike of research work due to the substantial improvements they have shown towards oxygen evolution reaction (OER) and hydrogen evolution reaction (HER). Oxygen vacancy engineering is an effective scheme to quintessentially tune the electronic structure and charge transport, generate secondary active surface phases, and modify the surface adsorption/desorption behavior of reaction intermediates during water splitting. Based on contemporary efforts for inducing oxygen vacancies in a variety of cobalt oxide types, this work addresses facile and environmentally benign synthesis strategies, characterization techniques, and detailed insight into the intrinsic mechanistic modulation of electrocatalysts. It is our foresight that appropriate utilization of the principles discussed herein will aid researchers in rationally designing novel materials that can outperform noble metal‐based electrocatalysts. Ultimately, future electrocatalysis implementation for selective seawater splitting is believed to depend on regulating the surface chemistry of active and stable TMOs. Lattice oxygen out, overpotential down: A clear reduction in electrocatalytic oxygen evolution reaction overpotential is typically witnessed upon fine‐tuning the degree of oxygen vacancies within a transition metal oxide lattice. Cobalt‐based metal oxides (Co−MO) are amongst the most promising electrocatalysts for water electrolysis. This Review offers a template for capitalizing on the realm of oxygen deficiency engineering atop Co−MO to reinforce their electrocatalytic performance. However, the intermittent shortcomings of the aforementioned renewable energy resources have limited their widespread deployment. An especially appealing approach to overcome this issue is to convert and store solar and wind‐derived energy in the form of chemical bonds such as hydrogen.The ever‐growing energy demand and the depletion of traditional fossil fuels have spurred continuous research efforts to deploy clean and renewable alternative energy resources such as solar energy and wind power.2) is an ideal energy carrier and has been widely conceded as a clean and sustainable carbon‐free energy source to replace non‐renewable carbon‐emitting fossil fuels owing to its high specific energy and environmental compatibility., or reaction of two adsorbed hydrogen atoms to form H2, known as the Tafel pathway . During the Heyrovsky reaction, the adsorbed hydrogen intermediate attracts an electron to produce a hydrogen molecule [Eq. (5)]. Similar to alkaline conditions, two adjacent absorbed hydrogen atoms chemically bond together to produce a hydrogen molecule via the Tafel reaction  and (10)]. In another route, a direct combination of two M−O species produces O2 [Eq. The first OER reaction step in alkaline media involves adsorption of the hydroxyl anion on the active site (M) and release of an electron to give M−OH [Eq. (7)]. Then, coupled proton and electron removals from M−OH takes place to form M−O [Eq. (8)]. Subsequently, oxygen formation follows two possible routes. In one route, M−O is converted to hydroperoxide M−OOH, and release of an electron after a hydroxyl anion is coupled. Then another proton‐coupled electron transfer process occurs to produce molecular Os O2 Eq. .[57]–2 formation can follow different routes that might or might not involve the formation of the M−OOH intermediate. at the Co K‐edge is displayed in Figure 2 samples. This suggests that the local structure of the B‐doped CoO−Ov electrocatalyst was markedly more disordered due to structural and electronic modulations from oxygen vacancies. Moreover, oxygen vacancies can be investigated by measuring the total electron yield intensity (TEY) from soft XAS (sXAS). Figure X‐ray absorption spectroscopy (XAS) is widely adopted method for studying the local geometric configurational changes and electronic structures of solids. Recently, X‐ray absorption near edge structure (XANES), a sub‐method of XAS, has been gaining traction as a feasible and accurate method in determining valence states of the adsorbing atom. Extended X‐ray absorption fine structure (EXAFS) is another reported sub‐category of XAS, which essentially probes the local chemical and electronic microenvironment on a material's surface. Liu and co‐workers4.30.9Ta0.1Oδ3‐. Primarily, the material is powdered and dissolved in HCl solution with excess potassium iodide (KI). Na2S2O3 solution was titrated into the above solution in order to determine the average oxidation state of Co ions. Sr and Ta were assumed to have fixed oxidation states of +2 and +5, respectively. Governed by charge electroneutrality conditions to be satisfied, the oxygen stoichiometry (lattice oxygen) and the degree of oxygen vacancies can be quantified.Iodometric titration (IT) was utilized by Wang et al.2. Briefly, when positrons are emitted into a solid sample, they interact with the present electrons and annihilate rapidly releasing gamma rays in a given recorded time . In the case of defects , the time it takes for annihilation is retarded, and as such the presence of these defects can be recorded. This method has been successfully used in identifying oxygen vacancies in hydrogenated TiO2 and cobalt oxides .Positron annihilation spectroscopy (PAS), also called positron annihilation lifetime spectroscopy (PALS), has also been reported for use in identifying oxygen vacancies in metal oxides. This characterization technique rapidly picked up in its reported utilization shortly after the discovery of oxygen deficient and disordered “black” TiOAll the aforementioned discussed techniques show a varying degree of accuracy and reliability in determining the presence of oxygen vacancies. However, based on our literature review of which characterization methods seem to be most accurate and reliable with respect to corresponding oxygen‐deficient TMO works, a pattern emerges. XPS, STM, XAS , and HRTEM seem to be the most reliable, followed by XRD, EPR, and IT. A major drawback to the excessive utilization of STM in more TMO characterization exists in the lack of high conductivity and ultra‐clean surfaces typically exhibited in TMOs, even those with surface oxygen deficiencies. XPS analyses innately limits characterization of oxygen vacancies in the first few surface layers. XRD studies of oxygen vacancies are only appropriate when dealing with highly crystalline materials. However, as will be discussed later in this work, several amorphous secondary active surface phases can exhibit oxygen vacancies and are primary sources of higher electrochemical activity in their respective materials. Thus, factoring for the fact that every technique exhibits some form of limitation, it has been accepted as a best practice to use multiple characterization techniques on the same material to undoubtedly prove the presence of oxygen vacancies.5− step, compared to 2‐e− steps for HER. Furthermore, an overwhelming majority of OER catalysts, including the benchmark IrO2 and RuO2, show poor stability in acidic media; TMOs tend to be utilized and investigated more for the alkaline OER process. Acidic conditions promote a lower overpotential for HER; however, due to metal oxide stability issues, not many are investigated for HER. Notwithstanding, this section will offer a comprehensive summary of experimental and computational explanations put forth from literature to better construe how oxygen vacancies promote TMOs electrocatalytic water splitting.The generation of surface oxygen vacancies can effectively modulate the surface morphology, electronic structure, and thus electrocatalytic properties of TMOs. Presence of these vacancies can markedly modify the interaction processes between the catalyst and reactants. Experimental and computational studies over the past decade have shed light on mechanistically explaining how oxygen vacancies can ameliorate high overpotentials in HER and OER of electrocatalytic metal oxides. Predominantly, three features were found to contribute to enhancements in performance, namely: changes in transport properties, the favorable formation of secondary active surface phases, and modulation of the bulk electronic structure. All of the aforementioned effects have a complementary impact on adsorption and desorption of reaction intermediates, potentially lowering rate‐determining thermodynamic and kinetic barriers. Generally, in water splitting the OER is limiting due to higher overpotentials as a result of it entailing 4‐e5.1Anion defects such as oxygen vacancies were directly related to enhance the electronic conductivity in TMOs. This design aspect is important since having a limiting charge transport would render an intrinsically active surface a poor electrocatalyst, consequentially decreasing OER performance.3O4 spinel type OER electrocatalyst fabricated by a plasma‐engraving procedure. This method did not only improve the intrinsic activity of Co3O4 by modifying the electronic states, but also by increasing the surface area through formulation of a porous surface, which exposed more active sites. Presence of oxygen vacancies was confirmed through a comparative analysis of the pristine and reduced spinel‐type TMO by employing XRD and XPS measurements. O 1s spectra from XPS analysis of plasma‐engraved reduced Co3O4 nanosheets in Figure 3O4. From a rather simplistic view, the ease of transference of two electrons existing at an oxygen vacancy defect state to the conduction band (CB) can be directly related to increased conductivity. Nyquist plots of OER on pristine and reduced spinel Co3O4 in Figure 3O4 nanosheets to obtain current density of 10 mA cm−2 and it showed very good stability after 2000 linear sweep voltammetry (LSV) cycles. This was 240 mV lower than pristine nanosheets due to the introduction of oxygen vacancies. As with many materials reported in literature, the enhancement in intrinsic catalytic performance of a material tends to be a combination of more than one fundamental aspect. In the case of plasma‐engraved reduced Co3O4, a combination of higher conductivity and exposed surface area resulted in substantial decrease in the required OER overpotential.The high availability of different coordination surface oxygen in spinel type TMOs promoted them as ideal candidates for enhancing OER performance upon introduction of oxygen vacancies. Wang et al.3O4 reduces the bandgap from approximately 1.5 to 0.8 eV. The OER thermodynamic overpotential for pristine Co3O4 was experimentally measured to be 470 mV at 10 mA cm−2. However, only 420 mV was required upon introduction of a single oxygen vacancy in their multi‐slab simulation. Experimentally determined HER performance was also shown to improve for the oxygen‐deficient spinel oxide, which was attributed to an enhanced conductivity.Through calculations of density of states (DOS) from density functional theory (DFT) approaches, Xiao et al.2O4, Sr2Fe1.3Ni0.2Mo0.5Oδ6‐, and Ca0.9Yb0.1MnO3 were also shown to enhance electronic conductivity and consequently improve OER activity. activity descriptors.It is essential to highlight that the major contribution that oxygen vacancies have towards performance improvement is to ultimately weaken, or strengthen, the binding energy of reaction intermediates to the electrocatalyst's surface. Thus, a rational employment of oxygen vacancy engineering should be undertaken. We accentuate that the synthesis of electrocatalysts should be preceded by a rational design based on fundamental understanding of how and what electronic, transport, and phase modulations are desired. Computationally aided theoretical calculations like density functional theory (DFT) have been widely adopted and accepted to initially screen and interpret enhancements in activity obtained upon introduction of oxygen vacancies. In this work, we point out the importance of DFT in identifying and appropriating intrinsic  and reaction‐based [i. e., ΔIt is worth noting that further investigation in other types of vacancy defects, both metallic and non‐metallic, may lead to development of highly active OER and HER materials. Defect engineering of carbonaceous materials such as graphene and graphdiyne  and utilizing them as supports for effective electrocatalysts can result in interesting phenomena in various applications, including water splitting. The careful examination of stability effects on electrocatalytic materials with defects is essential in the feasible implementation of these materials to commercial‐grade technologies. The hand‐to‐hand exploitation of machine learning, quantum mechanics, and experimental techniques to screen, characterize and study potential methods for stability enhancement is expected to revolutionize the scale of potential materials for water splitting applications. It is recommended that further studies using the environmentally benign, timely, and controllable utilization of plasma treatment strategies  are to be undertaken. Development of in situ techniques to characterize formation, location, content, and stability of oxygen vacancies and other point defects will prove very fruitful for the subsequent modeling and modulation of electrocatalysts.The authors declare no conflict of interest.Ahmed Badreldin obtained his M.Sc. in Chemical Engineering from Texas A&M University at Qatar in 2019. He is currently working on his PhD degree in Chemical Engineering at Texas A&M University. He has also been involved in the development of photocatalytic materials for water treatment and splitting, and on modelling systems of solid polymeric electrolytes using Mixed Anion Techniques for Lithium Ion Battery Development. Currently, Ahmed is planning on completing his PhD degree with primary focus on developing a highly functional seawater electrolyzer with novel durable and highly active electrocatalysts for industrially feasible implementation through experimental, DFT, and ML approaches.Aya E. Abusrafa obtained her M.Sc. in Chemical Engineering from Texas A&M University at Qatar in 2019. She is currently pursuing her PhD degree in Chemical Engineering from Texas A&M University. Her current research focus is on experimental electrocatalyst fabrication for overall water splitting. She was previously involved in computational fluid dynamic modeling of Fischer–Tropsch reactors using a novel Micro fibrous bed under nonconventional reaction media and surface modification of polymeric materials using plasma treatment.Prof. Ahmed Abdel‐Wahab is a Professor of Chemical Engineering at Texas A&M University at Qatar and a professor of Civil Engineering at Texas A&M University. His research primarily focuses on chemical, electrochemical, and photochemical processes associated with water and wastewater treatment, carbon dioxide reduction, and water splitting. This research has led to publication of more than 110 peer‐reviewed articles in leading research journals, 9 book chapters, and more than 80 refereed conference publications/presentations.