Alzheimer’s dementia (AD) is a progressive, neurodegenerative disease often accompanied by neuropsychiatric symptoms that profoundly impact both patients and caregivers. Agitation is among the most prevalent and distressing of these symptoms and often requires treatment. Appropriate therapeutic interventions depend on understanding the biological basis of agitation and how it may be affected by treatment. This narrative review discusses a proposed pathophysiology of agitation in Alzheimer’s dementia based on convergent evidence across research approaches. Available data indicate that agitation in Alzheimer’s dementia is associated with an imbalance of activity between key prefrontal and subcortical brain regions. The monoamine neurotransmitter systems serve as key modulators of activity within these brain regions and circuits and are rendered abnormal in AD. Patients with AD who exhibited agitation symptoms during life have alterations in neurotransmitter nuclei and related systems when the brain is examined at autopsy. The authors present a model of agitation in Alzheimer’s dementia in which noradrenergic hyperactivity along with serotonergic deficits and dysregulated striatal dopamine release contribute to agitated and aggressive behaviors.

We study the influence of a membrane filter's internal pore structure on its flow and adsorptive fouling behaviour. Membrane performance is measured via (1) comparison between volumetric flow rate and throughput during filtration and (2) control of concentration of foulants at membrane pore outlets. Taking both measures into account, we address the merits and drawbacks of selected membrane pore structures. We first model layered planar membrane structures with intra-layer pore connections, and present comparisons between non-connected and connected structures. Our model predicts that membrane filters with connected pore structures lead to higher total volumetric throughput than those with non-connected structures, over the filter lifetime. We also provide a sufficient criterion for the concentration of particles escaping the filter to achieve a maximum in time (indicative of a membrane filter whose particle retention capability can deteriorate). Additionally, we find that the influence of intra-layer heterogeneity in pore-size distribution on filter performance depends on the connectivity properties of the pores.

In this work we consider a new class of oscillatory instabilities that pertain to thermocapillary destabilization of a liquid film heated by a solid substrate. We assume the substrate thickness and substrate–film thermal conductivity ratio are large so that the effect of substrate thermal diffusion is retained at leading order in the long-wave approximation. As a result, the system dynamics is described by a nonlinear partial differential equation for the film thickness that is non-locally coupled to the full substrate heat equation. Perturbing about a steady quiescent state, we find that its stability is described by a non-self-adjoint eigenvalue problem. We show that, under appropriate model parameters, the linearized eigenvalue problem admits complex eigenvalues that physically correspond to oscillatory (in time) instabilities of the thin-film height. As the principal results of our work, we provide a complete picture of the susceptibility to oscillatory instabilities for different model parameters. Using this description, we conclude that oscillatory instabilities are more relevant experimentally for films heated by insulating substrates. Furthermore, we show that oscillatory instability where the fastest-growing (most unstable) wavenumber is complex, arises only for systems with sufficiently large substrate thicknesses. Finally, we discuss adaptation of our model to a practical setting and make predictions of conditions at which the reported instabilities can be observed.

Introduction: Patients with concussion often present to the emergency department (ED). Current guidelines recommend graded return to work and physical activity (i.e., sport, recreation and exercise activities); however, whether emergency physicians target this advice based on patient-reported activities is unknown. This study aimed to assess mismatches between physicians’ rest and return-to-activity advice and self-reported pre-injury work and physical activity of adult concussion patients. Methods: Adults (>17 years) presenting with a concussion from April 2013 to April 2015 to a study ED with Glasgow coma scale score ≥13 were recruited by on-site research assistants. Data on patient characteristics (i.e., age, sex, employment, and physical activity level) and activity leading to injury were collected from structured patient interviews. A structured questionnaire collected data from the treating physician about discharge advice provided. “Working” was defined as employed or enrolled in any level of school at the time of injury. “Physically active” was defined by reporting regular exercise (≥2 times a week) or concussed during a sports-related activity. Proportions or medians (interquartile range [IQR]) are reported, as appropriate. Results: Physician questionnaires were completed for 198/248 enrolled patients (median age: 37 years [IQR: 23, 49]; 46% male). Overall, 89% (177/198) were working; 110/177 (62%) received return-to-work advice, while 10/21 (48%) patients also received return-to-work advice, despite not working. Mentally strenuous work/school duties were reported by 143 patients, of which 85 (60%) were recommended cognitive rest. Overall, 148 patients were physically active and 115 (78%) of these were recommended physical rest while 124 (82%) were advised on safe return to physical activity. On the other hand, 35/50 (70%) patients who were not physically active received advice on safe return to physical activity. Sustaining a sports-related injury significantly increased the likelihood of safe return to physical activity advice among physically active patients (Fisher's exact p = 0.001). Conclusion: There is a mismatch between concussed patients’ pre-injury activities, and the rest and return-to-activity (i.e., work and physical activity) advice provided by emergency physicians. The possible effect of this mismatch on patient outcomes should be assessed in future research, as should strategies to improve emergency physician-patient communications around concussion management.

Introduction: Patients with concussion often present to the emergency department (ED). Although sports and recreation (SR) activities account for less than half of all adult concussions, guidelines developed for management of SR-related concussions (SRC) are widely used for all concussion patients. This study aimed to identify whether there are clinically relevant differences in patient and injury characteristics between SRC and those occurring outside of SR activities. Methods: Adults ( >17 years) presenting from April 2013 to April 2015 with a concussion to one of three EDs with Glasgow coma scale score ≥13 were recruited by on-site research assistants. Data on patient characteristics (i.e., age, sex, employment, lifestyle, relevant medical history), ED presentation (i.e., EMS arrival, hours since injury, CTAS, Glasgow Coma Scale score) and injury characteristics (i.e., activity leading to injury, loss of consciousness [LOC], signs and symptoms [scored using the Rivermead Post-Concussion Questionnaire], and health-related quality of life [from the 12-Item Short Form Health Survey [SF-12]) were collected from structured interviews and the ED chart. Dichotomous and categorical variables were compared using Fisher's exact test; continuous variables were compared using t-tests or Mann-Whitney tests, as appropriate. Results: In total, 248 patients were enrolled (47% male, median [IQR] age: 35 [23, 49]). Patients with SRC were younger (median: 23.5 years vs 35 years; p < 0.001), more likely to be a student (31% vs 8%; p > 0.001), and more likely to exercise regularly (89% vs 66%; p = 0.001). Patients with SRC were less likely to present during the daytime (66% vs. 77%; p = 0.022), less likely to have a history of mental health issues (18% vs 33%; p = 0.011) and had significantly higher median SF-12 physical components scores (55.5 [IQR: 51.4 to 57.8] vs. 53.5 [IQR: 45.5 to 56.7]; p = 0.025). All other characteristics were similar between the two groups. Conclusion: Although differences in demographics and lifestyle have been identified between patients sustaining a SRC and those concussed during other activities, injury characteristics, such as presentation acuity, proxies for severity, and signs and symptoms, were similar in both groups. Further analysis to assess whether the demographic and lifestyle differences affect clinical outcomes, such as time to symptom resolution, between these two groups is required to assess if sport-based treatment guidelines are appropriate for all patients.

Introduction: Continued smoking by cancer patients causes adverse cancer treatment outcomes, but few patients receive evidence-based smoking cessation as a standard of care.

Aim: To evaluate practical strategies to promote wide-scale dissemination and implementation of evidence-based tobacco cessation services within state cancer centers.

Methods: A Collaborative Learning Model (CLM) for Quality Improvement was evaluated with three community oncology practices to identify barriers and facilitate practice change to deliver evidence-based smoking cessation treatments to cancer patients using standardized assessments and referrals to statewide smoking cessation resources. Patients were enrolled and tracked through an automated data system and received follow-up cessation support post-enrollment. Monthly quantitative reports and qualitative data gathered through interviews and collaborative learning sessions were used to evaluate meaningful quality improvement changes in each cancer center.

Results: Baseline practice evaluation for the CLM identified the lack of tobacco use documentation, awareness of cessation guidelines, and awareness of services for patients as common barriers. Implementation of a structured assessment and referral process demonstrated that of 1,632 newly registered cancer patients,1,581 (97%) were screened for tobacco use. Among those screened, 283 (18%) were found to be tobacco users. Of identified tobacco users, 207 (73%) were advised to quit. Referral of new patients who reported using tobacco to an evidence-based cessation program increased from 0% at baseline across all three cancer centers to 64% (range = 30%–89%) during the project period.

Conclusions: Implementation of quality improvement learning collaborative models can dramatically improve delivery of guideline-based tobacco cessation treatments to cancer patients.

Introduction: Patients with concussion frequently present to the emergency department (ED). Studies of athletes and children indicate that concussion symptoms are often more severe and prolonged in females compared with males. To-date, study of sex-based concussion differences in general adult populations have been limited. This study examined sex-based differences in concussion outcomes. Methods: Adult (>17 years) patients presenting to one of three urban EDs in Edmonton, Alberta with Glasgow coma scale score 13 within 72 hours of a concussive event were recruited by on-site research assistants. Follow-up calls at 30 and 90 days post ED discharge captured extent of PCS using the Rivermead Post-Concussion questionnaire (RPQ), effect on daily living activities measured by the Rivermead Head Injury Questionnaire (RHIQ), and overall health-related quality of life using the 12-item Short Form Health Survey (SF-12). Dichotomous and categorical variables were compared using Fishers exact test; continuous variables were compared using t-tests or Mann-Whitney tests, as appropriate. Results: Overall, 130/250 enrolled patients were female. The median age was 35 years; men trended towards being younger (median=32 years; IQR: 23, 45) than women (median=40 years; IQR: 22, 52). Compared to women, more men were single (56% vs 38% (p=0.007) and employed (82% vs 71% (p=0.055). Men and women experienced different injury mechanisms (p=0.007) with more women reporting injury due to a fall (44% vs 26%), while more men were injured at work (16% vs 7%) or due to an assault (11% vs. 3%). Men had a higher return to ED rate (13% vs. 5%; p=0.015). Women had higher RPQ scores at baseline (p<0.001) and 30-day follow-up (p=0.001); this difference was not significant by 90 days (p=0.099). While women reported on the RHIQ at 30 days that their injury affected their usual activities significantly more than men (Median=5, IQR: 0, 11 vs. median=0.5, IQR: 0.5, 7; p=0.004), both groups had similar scores on the SF-12 physical composite and mental composite scales at all three measurement points. Conclusion: In a general ED concussion population, demographic differences exist between men and women. Based on self-reported and objective outcomes, womens usual activities may be more affected by concussion and PCS than men. Further analysis of these differences is required in order to identify different treatment options and ensure adequate care and treatment of injury.

Introduction: Patients with mild traumatic brain injury (mTBI) frequently present to the emergency department (ED); however, wide variation in diagnosis and management has been demonstrated in this setting. Sub-optimal mTBI management can contribute to post-concussion syndrome (PCS), affecting vocational outcomes like return to work. This study documented the work-related events, ED management, discharge advice, and outcomes for employed patients presenting to the ED with mTBI. Methods: Adult (>17 years) patients presenting to one of three urban EDs in Edmonton, Alberta with Glasgow coma scale score ≥13 within 72 hours of a concussive event were recruited by on-site research assistants. Follow-up calls ascertained outcomes, including symptoms and their severity, advice received in the ED, and adherence to discharge instructions, at 30 and 90 days after ED discharge. Dichotomous variables were analyzed using chi-square testing; continuous variables were compared using t-tests or Mann-Whitney tests, as appropriate. Work-related injury and return to work outcomes were modelled using logistic or linear regression, as appropriate. Results: Overall, 250 patents were enrolled; 172 (69%) were employed at the time of their injury and completed at least one follow-up. The median age was 37 years (interquartile range [IQR]: 24, 49.5), both sexes were equally represented (48% male), and work-related concussions were uncommon (16%). Work-related concussion was related to manual labor jobs and self-reported history of attention deficit disorder. Patients often received advice to avoid sports (81%) and/or work (71%); however, the duration of recommended time off varied. Most employed patients (80%) missed at least one day of work (median=7 days; IQR: 3, 14); 91% of employees returned to work by 90 days, despite 41% reporting persistent symptoms. Increased days of missed work were linked to divorce, history of sleep disorder, and physician’s advice to avoid work. Conclusion: While work-related concussions are uncommon, most employees who sustain a mTBI at any time miss some work. Many patients experience mTBI symptoms past 90 days, which has serious implications for workers’ abilities to fulfill their work duties and risk of subsequent injury. Workers, employers, and the workers compensation system should take the necessary precautions to ensure that workers return to work safely and successfully following a concussion.

Introduction: Patients with mild traumatic brain injury (mTBI) often present to the emergency department (ED). Incorrect diagnosis may delay appropriate treatment and recommendations for these patients, prolonging recovery. Notable proportions of missed mTBI diagnosis have been documented in children and athletes, while diagnosis of mTBI has not been examined in the general adult population. Methods: A prospective cohort study was conducted in one academic (site 1) and two non-academic (sites 2 and 3) EDs in Edmonton, Canada. On-site research assistants enrolled adult (>17 years) patients presenting within 72 hours of the injury event with clinical signs of mTBI and Glasgow comma scale score ≥13. Patient demographics, injury characteristics, and ED flow information were collected by chart review. Physician-administered questionnaires and patient interviews documented the recommendations given by emergency physicians at discharge. Bi-variable comparisons are reported using Pearson’s chi-square tests, Student’s t-tests or Mann-Whitney tests, as appropriate. Multivariate analyses were performed using logistic regression methods. Results: Overall, 130/250 enrolled patients were female, and the median age was 35. Proportions of successfully diagnosed mTBI varied significantly across study sites (Site 1: 89%; Site 2: 73%, Site 3: 53%; p>0.001). Patients without a diagnosis were less likely to receive a recommendation to follow-up with their family physician (OR=0.08; 95% CI: 0.03, 0.21) or advice about return to work (OR=0.17; 95% CI: 0.08, 0.04) or physical activity (OR=0.08; 95% CI: 0.04, 0.17). Patients with missed diagnoses had longer ED stays (median=5.0 hours; IQR: 3.8, 7.0) compared with diagnosed mTBI patients (median=3.9 hours; IQR: 3.0, 5.3). In the adjusted model, patients presenting to non-academic centers had reduced likelihood of mTBI diagnosis (Site 2: OR=0.21; 95% CI: 0.08, 0.58; Site 3: OR=0.07; 95% CI: 0.02, 0.24). Conclusion: The diagnostic accuracy of physicians assessing patients presenting with symptoms of mTBIs to these three EDs is suboptimal. The rates of missed diagnosis vary among EDs and were associated with length of ED stay. Closer examination of institutional factors, including diagnosis processes and personnel factors such as physician training, is needed to identify effective strategies to heighten the awareness of mTBI presentations.

Membrane filters are used extensively in microfiltration applications. The type of membrane used can vary widely depending on the particular application, but broadly speaking the requirements are to achieve fine control of separation, with low power consumption. The solution to this challenge might seem obvious: select the membrane with the largest pore size and void fraction consistent with the separation requirements. However, membrane fouling (an inevitable consequence of successful filtration) is a complicated process, which depends on many parameters other than membrane-pore size and void fraction; and which itself greatly affects the filtration process and membrane functionality. In this work we formulate mathematical models that can (i) account for the membrane internal morphology (internal structure, pore size and shape, etc.); (ii) describe fouling of membranes with specific morphology; and (iii) make some predictions as to what type of membrane morphology might offer optimum filtration performance.

A new diatom record from Lake Victoria’s Pilkington Bay, subsampled at 21- to 25-year intervals and supported by 20 AMS dates, reveals a ∼10,000 calendar year environmental history that is supported by published diatom and pollen data from two nearby sites. With their chronologies adjusted here to account for newly documented ancient carbon effects in the lake, these three records provide a coherent, finely resolved reconstruction of Holocene climate change in equatorial East Africa. After an insolation-induced rainfall maximum ca. 8800–8300 cal yr B.P., precipitation became more seasonal and decreased abruptly ca. 8200 and 5700 yr B.P. in apparent association with northern deglaciation events. Century-scale rainfall increases occurred ca. 8500, 7000, 5800, and 4000 yr B.P. Conditions after 2700 yr B.P. were generally similar to those of today, but major droughts occurred ca. 1200–600 yr B.P. during Europe’s Medieval Warm Period.

The reader might get the impression that the four projects described in this Special Section proceeded in a systematic and predictable way. Of course, those of us engaged in each research project encountered pitfalls and challenges along the way. A main goal of this Special Section is to provide pathways and encouragement for those who may be interested in advancing high-quality research on this topic. In this paper, we describe a set of practical and ethical challenges that we encountered in conducting our longitudinal, process-oriented, and translational research with conflict-affected youth, and we illustrate how problems can be solved with the goal of maintaining the internal and external validity of the research designs. We are hopeful that by describing the challenges of our work, and how we overcame them, which are seldom treated in this or any other literature on research on child development in high-risk contexts, we can offer a realistic and encouraging picture of conducting methodologically sound research in conflict-affected contexts.

This study examined the transactional interplay among dimensions of destructive interparental conflict (i.e., hostility and dysphoria), children's emotional insecurity, and their psychological problems from middle childhood and adolescence. Participants were 232 families, with the first of five measurement occasions occurring when children were in first grade (M age = 7 years). Cross-lagged, autoregressive models were conducted with a multiple-method, multiple-informant measurement approach to identify developmental cascades of interparental and child cascades. Results indicated that emotional insecurity was a particularly powerful mediator of prospective associations between interparental conflict (i.e., dysphoria and hostility) and child adjustment during adolescence rather than childhood. In reflecting bidirectionality in relationships between interparental and child functioning, children's psychological problems predicted increases in interparental dysphoria during childhood and adolescence. Although emotional insecurity was not identified as a proximal predictor of interparental difficulties, an indirect cascade was identified whereby insecurity in early adolescence was associated with increases in teen psychological problems, which in turn predicted greater interparental dysphoria over time. Results are interpreted in the context of how they advance transactional formulation of emotional security theory and its resulting translational implications for clinical initiatives.

Pleated membrane filters are widely used in many applications, and offer significantly better surface area to volume ratios than equal-area unpleated membrane filters. However, their filtration characteristics are markedly inferior to those of equivalent unpleated membrane filters in dead-end filtration. While several hypotheses have been advanced for this, one possibility is that the flow field induced by the pleating leads to spatially non-uniform fouling of the filter, which in turn degrades performance. In this paper we investigate this hypothesis by developing a simplified model for the flow and fouling within a pleated membrane filter. Our model accounts for the pleated membrane geometry (which affects the flow), for porous support layers surrounding the membrane, and for two membrane fouling mechanisms: (i) adsorption of very small particles within membrane pores; and (ii) blocking of entire pores by large particles. We use asymptotic techniques based on the small pleat aspect ratio to solve the model, and we compare solutions to those for the closest-equivalent unpleated filter.

Although cattle movement and commingling play an important role in the inter-herd transmission of pathogens, little is known about the effect of commingling of heifers at raising operations. The objective of this study was to compare the resistance of E. coli and prevalence of Salmonella from pooled faecal pats of heifers raised off-farm at multi-source raisers (MULTI) that raised heifers from at least two farms compared with on-farm raisers (HOME), with heifers from only that farm. MULTI faecal pat samples were collected from pens with animals that had arrived at the farm within the previous 2 months (AP) and from animals that would be departing the heifer raiser in 2–3 months (DP). Corresponding age sampling was conducted at HOME raisers. Odds of ampicillin resistance were 3·0 times greater in E. coli collected from MULTI compared to HOME raisers. E. coli from AP pens had significantly (P < 0·05) higher odds of resistance to ampicillin, neomycin, streptomycin, and tetracycline compared to DP pens. Salmonella recovery was not significantly different between heifer-raising systems (P = 0·3). Heifer-raising system did not have a major overall impact on selection of resistant E. coli, which was strongly affected by the age of the animals sampled.