Windows of opportunity for predicting seasonal climate extremes highlighted by the Pakistan floods of 2022.

Skilful predictions of near-term climate extremes are key to a resilient society. However, standard methods of analysing seasonal forecasts are not optimised to identify the rarer and most impactful extremes. For example, standard tercile probability maps, used in real-time regional climate outlooks, failed to convey the extreme magnitude of summer 2022 Pakistan rainfall that was, in fact, widely predicted by seasonal forecasts. Here we argue that, in this case, a strong summer La Niña provided a window of opportunity to issue a much more confident forecast for extreme rainfall than average skill estimates would suggest. We explore ways of building forecast confidence via a physical understanding of dynamical mechanisms, perturbation experiments to isolate extreme drivers, and simple empirical relationships. We highlight the need for more detailed routine monitoring of forecasts, with improved tools, to identify regional climate extremes and hence utilise windows of opportunity to issue trustworthy and actionable early warnings.

Quantitative Raman chemical imaging of intracellular drug-membrane aggregates and small molecule drug precipitates in cytoplasmic organelles.

Raman confocal microscopes have been used to visualize the distribution of small molecule drugs within different subcellular compartments. This visualization allows the discovery, characterization, and detailed analysis of the molecular transport phenomena underpinning the Volume of Distribution - a key parameter governing the systemic pharmacokinetics of small molecule drugs. In the specific case of lipophilic small molecules with large Volumes of Distribution, chemical imaging studies using Raman confocal microscopes have revealed how weakly basic, poorly soluble drug molecules can accumulate inside cells by forming stable, supramolecular complexes in association with cytoplasmic membranes or by precipitating out within organelles. To study the self-assembly and function of the resulting intracellular drug inclusions, Raman chemical imaging methods have been developed to measure and map the mass, concentration, and ionization state of drug molecules at a microscopic, subcellular level. Beyond the field of drug delivery, Raman chemical imaging techniques relevant to the study of microscopic drug precipitates and drug-lipid complexes which form inside cells are also being developed by researchers with seemingly unrelated scientific interests. Highlighting advances in data acquisition, calibration methods, and computational data management and analysis tools, this review will cover a decade of technological developments that enable the conversion of spectral signals obtained from Raman confocal microscopes into new discoveries and information about previously unknown, concentrative drug transport pathways driven by soluble-to-insoluble phase transitions occurring within the cytoplasmic organelles of eukaryotic cells.

Aged mice are less susceptible to motion sickness and show decreased efferent vestibular activity compared to young adults.

INTRODUCTION: The efferent vestibular system (EVS) is a feedback circuit thought to modulate vestibular afferent activity by inhibiting type II hair cells and exciting calyx-bearing afferents in the peripheral vestibular organs. In a previous study, we suggested EVS activity may contribute to the effects of motion sickness. To determine an association between motion sickness and EVS activity, we examined the effects of provocative motion (PM) on c-Fos expression in brainstem efferent vestibular nucleus (EVN) neurons that are the source of efferent innervation in the peripheral vestibular organs. METHODS: c-Fos is an immediate early gene product expressed in stimulated neurons and is a well-established marker of neuronal activation. To study the effects of PM, young adult C57/BL6 wild-type (WT), aged WT, and young adult transgenic Chat-gCaMP6f mice were exposed to PM, and tail temperature (Ttail ) was monitored using infrared imaging. After PM, we used immunohistochemistry to label EVN neurons to determine any changes in c-Fos expression. All tissue was imaged using laser scanning confocal microscopy. RESULTS: Infrared recording of Ttail during PM indicated that young adult WT and transgenic mice displayed a typical motion sickness response (tail warming), but not in aged WT mice. Similarly, brainstem EVN neurons showed increased expression of c-Fos protein after PM in young adult WT and transgenic mice but not in aged cohorts. CONCLUSION: We present evidence that motion sickness symptoms and increased activation of EVN neurons occur in young adult WT and transgenic mice in response to PM. In contrast, aged WT mice showed no signs of motion sickness and no change in c-Fos expression when exposed to the same provocative stimulus.

Molecular and Functional Changes to Postsynaptic Cholinergic Signaling in the Vestibular Sensory Organs of Aging C57BL/6 Mice.

Cholinergic circuits in the central nervous system are vulnerable to age-related functional decline, but it is not known if aging impacts cholinergic signaling in the vestibular sensory organs, which are critically important to balance maintenance and visual gaze stability. We have previously shown cholinergic neurotransmission between vestibular efferent terminals and type II mechanosensory hair cells requires the alpha9 (Chrna9) nicotinic receptor subunit. Homozygous knockout of the alpha9 subunit causes vestibulo-ocular reflex adaptation deficits that mirror those observed in aged mice. This prompted examination of cholinergic signaling in the vestibular sensory organs of aged mice. We confirmed older (>24 months) mice had impaired performance in a balance beam task compared to young (3-4 months) adult mice. While there was no qualitative loss of cholinergic axon varicosities in the crista ampullaris of old mice, qPCR analysis revealed reduced expression of nicotinic receptor subunit genes Chrna1, Chrna9, and Chrna10 in the cristae of old relative to young mice. Functionally, single-cell patch clamp recordings taken from type II vestibular hair cells exposed to acetylcholine show reduced conductance through alpha9/10 subunit-containing nicotinic receptors in older mice, despite preserved passive membrane properties and voltage-activated conductances. These findings suggest that cholinergic signaling in the peripheral vestibular sensory organs is vulnerable to aging processes, manifesting in dynamic molecular and functional age-related changes. Given the importance of these organs to our everyday activities, and the dramatic increase in fall incidence in the older, further investigation into the mechanisms of altered peripheral vestibular function in older humans is warranted.

Rationale and design of an ancillary study evaluating the effects of the cocoa flavanol and/or multivitamin interventions on falls and physical performance outcomes in the COcoa Supplement and Multivitamin Outcomes Study (COSMOS).

BACKGROUND: Falls and decreased physical function increase markedly with age and result in injury, hospitalization, and premature death. Emerging studies show potential benefits of supplemental cocoa extract on physical performance, including grip strength and walking speed in older adults. However, there are no large, long-term randomized controlled trials of effects of supplemental cocoa extract on falls, muscle performance, and/or fall-related injuries. METHODS: The COcoa Supplement and Multivitamin Outcomes Study (COSMOS) is a double-blind, placebo-controlled, 2 × 2 factorial trial investigating effects of supplementation with cocoa extract (500 mg/d, including 80 mg (-)-epicatechin) and/or a multivitamin on prevention of cardiovascular disease and cancer in 21,442 women (≥65 years) and men (≥60 years). COSMOS: Effects on Falls and Physical Performance is an ancillary study to COSMOS that will clarify effects of cocoa extract and/or multivitamin supplementation on falls, physical performance, and incident fracture outcomes in older adults. Injurious fall(s) resulting in healthcare utilization and recurrent falls were regularly assessed by follow-up questionnaires in the overall cohort. Incident fractures were also assessed by annual questionnaires. Circumstances surrounding falls and any fall-related injuries will be confirmed by medical record review. Effects of the interventions on 2-year changes in physical performance measures (grip strength, walking speed, and the Short Physical Performance Battery) will be tested in a clinic sub-cohort (n = 603). CONCLUSION: Results from this ancillary study will determine whether supplemental cocoa extract slows age-related declines in physical performance and decrease injurious and recurrent falls and fall-related injuries and fractures that are major public health problems in older adults.

Measuring the Impact of MyLupusGuide in Canada: Results of a Randomized Controlled Study.

OBJECTIVE: This study was undertaken to assess the effects of a web-based program, MyLupusGuide, developed to facilitate self-management in systemic lupus erythematosus (SLE). METHODS: In this randomized controlled online study, participants received either immediate access to the MyLupusGuide site or delayed access starting on month 3. The primary outcome was the patient activation measure (PAM) score. Secondary outcomes included measurements of health status, self-efficacy, coping, perceived patient-physician relationship, and medication adherence. Outcomes were measured at the baseline visit and at the 3-month and 6-month follow-up visits. We used linear mixed modeling to compare PAM scores between the 2 groups at months 3 and 6. RESULTS: There were 541 participants included in this study. The mean ± SE age was 50 ± 14 years; 93% were female and 74% were White. The mean ± SE disease duration was 17 ± 12 years, and 56% visited MyLupusGuide at least once. The baseline mean ± SE PAM score was 61.2 ± 13, with 36% scoring low for perceived self-management skills. After 3 months of exposure to MyLupusGuide, there were no differences in terms of PAM scores between groups. In exploratory analyses, we found significant improvement in PAM scores in those who had low PAM scores at baseline and in male individuals. We observed significant improvements in self-efficacy before and after access to MyLupusGuide and delayed improvements at month 6 compared to month 3 in terms of mental health and emotional coping. CONCLUSION: MyLupusGuide increases self-efficacy but not patient activation. A total of 56% of participants visited the MyLupusGuide site during the study period. Individuals with lupus need support to become activated toward self-management behaviors.

Relationships between Lower-body Power, Sprint and Change of Direction Speed among Collegiate Basketball Players by Sex.

The purpose of this study was to determine if significant relationships exist between absolute and relative lower-body power and selected measures of speed among male and female collegiate basketball players. Archived performance testing data from 29 (male = 14; female = 15) NCAA division II collegiate basketball players were used for this analysis. These measures included lane agility, 10-yard sprint, and shuttle run time (sec). A Pearson's correlation coefficient was used to determine if significant relationships existed between measures of lower-body power and linear sprint time, change of direction speed (CODS), and shuttle performance. Statistical significance was set a priori at p ≤ 0.05. A significant large correlation was found between absolute power and lane agility (r = 0.54, p = 0.05) among male players. No significant correlations were found between absolute or relative power for 10-yard sprint times, lane agility, or shuttle run performance (p > 0.05). Females showed no significant correlations between relative power and lane agility (r = -0.25, p = 0.37) or 10-yard sprint (r = -0.47, p = 0.08), but did show a significant large correlation (r = -0.64, p = 0.01) between relative power and shuttle run performance. Generating high amounts of relative power is vital in intermittent team sports such as basketball. In particular, this study provided evidence that relative power in female collegiate basketball players is significantly related to shuttle run ability.

Kinanthropometric Characteristic Comparisons of NCAA Division I Offensive and Defensive Linemen Spanning 8 Decades.

ABSTRACT: Jacobson, BH, Dawes, J, Smith, D, and Johnson, Q. Kinanthropometric characteristic comparisons of NCAA Division I offensive and defensive linemen spanning eight decades. J Strength Cond Res 36(12): 3404-3408, 2022-College football players have gained body mass, stature, and speed since the inception of the game. Of particular note is the body mass gain of NCAA Division I offensive linemen (OL) and defensive linemen (DL). The primary purpose of this study was to compare body mass and stature of OL and DL for each decade since 1950 and to subsequently compare speed using more recently available NFL Combine data to determine if the rates of gain have been consistent or is waning. Ten universities were randomly chosen from the "Power Five" conferences based on the prominence of their football programs. Recorded data included players' body mass, stature, and available 40 yd times. For each team, 8 OL and 8 DL were chosen, totaling 80 OL and 80 DL. Results indicated that body mass increased significantly ( p < 0.05) for both OL and DL (57.9 and 54.4%, respectively). However, the rate of weight gain for either OL or DL was not linear. Both OL and DL consistently increased in height from 1950 with OL and DL increasing 12.7 cm (5.0 in) and 11.4 cm (4.7 in), respectively. In addition, 40 yd times have improved over the 3 available decades (2000-2020). The 2020 times were significantly faster than the 2000 for both OL and DL. These findings may have profound implications related to player safety. The overall increases in body mass of linemen in combination with greater speed may result in have devastating consequences to the human body in a contact/collision sport such as football. Indeed, new rules are being considered to reduce debilitating injures.

Adolescent Substance Use and Individual Beliefs That Drug Use Is Wrong: A Statewide Epidemiological Study.

OBJECTIVE: Informed by cognitive dissonance theory, the current study investigated the ability of youths' belief that drug use is wrong to predict likelihood of past year substance use abstinence as well as frequency of use at grades 8, 10, and 12. METHOD: Study analyses were executed from a statewide epidemiological survey of more than 125,000 youth using multi-group Zero-Inflated Poisson regression modeling. RESULTS: Personal belief that drug use is wrong demonstrated the largest magnitude of effect at each grade among the individual, family, and school-based factors under examination; this finding emerged with respect to predicting past year substance use abstinence as well as rates of substance use among individuals reporting past year use. Although differences across grades were evident for the magnitude of effect within various risk and protective factors, the rank ordering in magnitude of effect between factors was consistent across grades 8, 10, and 12. CONCLUSION: Current results underscore the salience of youths' belief that drug use is wrong in explaining likelihood of past year substance use at multiple time points during adolescence.Supplemental data for this article is available online at https://doi.org/10.1080/10826084.2022.2034877 .

The Functional Resonance Analysis Method as a health care research methodology: a scoping review.

OBJECTIVE: The objective of this review was to examine and map the literature on the use of the Functional Resonance Analysis Method (FRAM) in health care research. INTRODUCTION: The FRAM is a resilient health care tool tat offers an approach to deconstruct complex systems by mapping health care processes to identify essential activities, how they are interrelated, and the variability that emerges, which can strengthen or compromise outcomes. Insight into how the FRAM has been operationalized in health care can help researchers and policy-makers understand how this method can be used to strengthen health care systems. INCLUSION CRITERIA: This scoping review included research and narrative reports on the application of the FRAM in any health care setting. The focus was to identify the key concepts and definitions used to describe the FRAM; the research questions, aims, and objectives used to study the FRAM; the methods used to operationalize the FRAM; the health care processes examined; and the key findings. METHODS: A three-step search strategy was used to find published and unpublished research and narrative reports conducted in any country. Only papers published in English were considered. No limits were placed on the year of publication. CINAHL, MEDLINE, Embase, PsycINFO, Inspec Engineering Village, ProQuest Nursing & Allied Health were searched originally in June 2020 and again in March 2021. A search of the gray literature was also completed in March 2021. Data were extracted from papers by two independent reviewers using a data extraction tool developed by the reviewers. Search results are summarized in a flow diagram, and the extracted data are presented in tabular format. RESULTS: Thirty-one papers were included in the final review, and most (n = 25; 80.6%) provided a description or definition of the FRAM. Only two (n = 2; 6.5%) identified a specific research question. The remaining papers each identified an overall aim or objective in applying the FRAM, the most common being to understand a health care process (n = 20; 64.5%). Eleven different methods of data collection were identified, with interviews being the most common (n = 21; 67.7%). Ten different health care processes were explored, with safety and risk identification (n = 8; 25.8%) being the most examined process. Key findings identified the FRAM as a mapping tool that can identify essential activities or functions of a process (n = 20; 64.5%), how functions are interdependent or coupled (n = 18; 58.1%), the variability that can emerge within a process (n = 20; 64.5%), discrepancies between work as done and work as imagined (n = 20; 64.5%), the resiliency that exists within a process (n = 12; 38.7%), and the points of risk within a process (n = 10, 32.3%). Most papers (n = 27; 87.1%) developed models representing the complexity of a process. CONCLUSIONS: The FRAM aims to use a systems approach to examine complex processes and, as evidenced by this review, is suited for use within the health care domain. Interest in the FRAM is growing, with most of the included literature being published since 2017 (n = 24; 77.4%). The FRAM has the potential to provide comprehensive insight into how health care work is done and how that work can become more efficient, safer, and better supported.

Challenges of Perceived Self-Management in Lupus.

OBJECTIVE: Systemic lupus erythematosus is a chronic autoimmune disease with varied and unpredictable levels of disease activity. The ability to self-manage lupus is important in controlling disease activity. Our objective was to determine levels of patient activation toward self-management in lupus. METHODS: We used baseline results from the MyLupusGuide study, which had recruited 541 lupus patients from 10 lupus centers. We used the Patient Activation Measure (PAM), a validated self-reported tool designed to measure activation toward self-management ability, as our primary variable and examined its association with demographic, disease-related, patient-provider communication and psychosocial variables captured in our study protocol. Univariable and multivariable linear regressions were performed using linear mixed models, with a random effect for centers. RESULTS: The mean ± SD age of participants was 50 ± 14 years, 93% were female, 74% were White, and the mean ± SD disease duration was 17 ± 12 years. The mean ± SD PAM score was 61.2 ± 13.5, with 36% of participants scoring in the 2 lower levels, indicating low activation. Variables associated with low activation included being single, having lower physical health status, lower self-reported disease activity, lower self-efficacy, use of more emotional coping and fewer distraction and instrumental coping strategies, and a perceived lack of clarity in patient-doctor communication. CONCLUSION: Low patient activation was observed in more than one-third of lupus patients, indicating that a large proportion of patients perceived that they are lacking in lupus self-management skills. These results highlight a modifiable gap in perceived self-management ability among patients with lupus.

Suicidal Ideation Among Transgender and Gender Expansive Youth: Mechanisms of Risk.

Purpose: Suicide is a leading public health concern among transgender and gender expansive adolescents, although little research has examined mechanisms through which gender identity is associated with suicidal ideation. This study examined the indirect effects of peer victimization, dating violence, substance use (SU), SU problems, and depressive symptoms in the relationship between gender identity and suicidal ideation. Methods: Secondary data analysis was conducted from a 2018 statewide survey, including 4464 adolescents who identified as male, female, transgender, or gender expansive (n=1116 per gender). The sample was frequency matched on grade, race, geographic region, and free/reduced lunch status. Mediation analyses were performed. Results: Reports of suicidal ideation were highest among transgender (49.29%) and gender expansive (41.31%) adolescents compared with male (10.82%) and female adolescents (19.08%). Using the Karlson, Holm, and Breen approach, 50.45% of the effect of being transgender on suicidal ideation was mediated through peer victimization, dating violence, and depressive symptoms, and 39.29% through SU, SU problems, and depressive symptoms. The mediation through the same pathways for being gender expansive was 46.37% and 39.89%, respectively. Across both models, depressive symptoms predominately accounted for the mediating effect. Conclusion: Transgender and gender expansive youth are at alarming risk for suicidal ideation, which illustrates the critical need for suicide prevention within this population. Programs that promote mental health and work to prevent bullying, dating violence, SU, and SU problems are crucial; although longitudinal research is needed, targeting these mechanisms may play a critical role in reducing suicidal ideation and risk.

A knowledge elicitation study to inform the development of a consequence model for Arctic ship evacuations: Qualitative and quantitative data.

Expert knowledge was elicited to develop a life-safety consequence severity model for Arctic ship evacuations (Browne et al., 2021). This paper presents the associated experimental design and data. Through semi-structured interviews, participants identified factors that influence consequence severity. Through a survey, participants evaluated consequence severity of different ship evacuation scenarios. The methodology represents a two-phased mixed methods design. Life-safety consequence severity is measured as the expected number of fatalities resulting from an evacuation. Participants of the study were experts in various fields of the Arctic maritime industry. Sixteen experts participated in the interviews and the survey (sample size: n = 16). Sample size for the interviews was based on thematic data saturation. Predominantly the same group of experts participated in the survey. Interviews were analysed using thematic analysis. Interview data informed the development of evacuation scenarios defined in the survey. The interview guide and survey questions are presented. Data tables present the codes that emerged through thematic analysis, including code reference counts and code intersection counts. Data tables present the raw data of participant responses to the survey. This data can support further investigation of factors that influence consequence severity, definition of a broader range of evacuation scenarios, and establishment of associated consequence severities. This data has value to Arctic maritime policy-makers, researchers, and other stakeholders engaged in maritime operational risk management.

Decadal climate variability in the tropical Pacific: Characteristics, causes, predictability, and prospects.

Climate variability in the tropical Pacific affects global climate on a wide range of time scales. On interannual time scales, the tropical Pacific is home to the El Niño­Southern Oscillation (ENSO). Decadal variations and changes in the tropical Pacific, referred to here collectively as tropical Pacific decadal variability (TPDV), also profoundly affect the climate system. Here, we use TPDV to refer to any form of decadal climate variability or change that occurs in the atmosphere, the ocean, and over land within the tropical Pacific. "Decadal," which we use in a broad sense to encompass multiyear through multidecadal time scales, includes variability about the mean state on decadal time scales, externally forced mean-state changes that unfold on decadal time scales, and decadal variations in the behavior of higher-frequency modes like ENSO.

A dynamic version of the FRAM for capturing variability in complex operations.

Functional Resonance Analysis Method (FRAM) is a function-based approach to model complex socio-technical systems and to manage variability. The current FRAM related tools are unable to capture qualitative and quantitative characteristics of variability as well as temporal variations. This study presents in detail a dynamic FRAM-based tool, which is called DynaFRAM. It is introduced to address the variability-related deficiencies of the FRAM related tools. It aims to capture variability in complex operations. It is a dynamic tool developed to capture time related variations in complex operations. This increases the attractiveness of the DynaFRAM for complex operations where specialists and practitioners make decisions in complicated situations. The ability of the DynaFRAM is demonstrated by examining a healthcare related case study. Although the ability of the DynaFRAM is assessed through capturing variations in healthcare operations, it can be applied to other domains in a similar manner.•The DynaFRAM is a dynamic FRAM-based tool.•It is able to captures different characteristics of variability.•It facilitates understanding and analysis of variability in complex operations.

One size does not fit all: Toward regional conservation practice guidance to reduce phosphorus loss risk in the Lake Erie watershed.

Agricultural phosphorus (P) losses to surface water bodies remain a global eutrophication concern, despite the application of conservation practices on farm fields. Although it is generally agreed upon that the use of multiple conservation practices ("stacking") will lead to greater improvements to water quality, this may not be cost effective to farmers, reducing the likelihood of adoption. At present, wholesale recommendations of conservation practices are given; however, the application of specific conservation practices in certain environments (e.g., no-till with surface application, cover crops) may not be effective and can even lead to unintended consequences. In this paper, we present the Lake Erie watershed as a case study. The Lake Erie watershed contains regions with unique physical geographies that include differences in climate, soil, topography, and land use, which have implications for both P transport from agricultural fields and the efficacy of conservation practices in mitigating P losses. We define major regions within the Lake Erie watershed where common strategies for conservation practice implementation are appropriate, and we propose a five-step plan for bringing regionally tailored, adaptive, and cost-conscious conservation practice into watershed planning. Although this paper is specific to the Lake Erie watershed, our framework can be transferred across broader geographic regions to provide guidance for watershed planning.

Modeling and analyzing hospital to home transition processes of frail older adults using the functional resonance analysis method (FRAM).

The main purpose of this study was to model and analyze hospital to home transition processes of frail older adults in order to identify the challenges within this process. A multi-phase, multi-sited and mixed methods design was utilized, in which, Phase 1 included collecting semi-structured interviews and focus group data, and Phase 2 consisted of six patient/caregiver dyad prospective case studies. This study was conducted in three hospitals in three cities in a single province in Canada. The Functional Resonance Analysis Method (FRAM) was employed to model daily operations of the transition process. The perspectives of both healthcare providers and patients/caregivers were used to build the FRAM model. The transition model was then tested using a customized version of the FRAM. The six patient/caregiver cases were used in the process of testing the FRAM model. The results of building the FRAM model showed that five categories of functions contributed to the transition model, including admission, assessment, synthesis, decision-making, and readmission. The outcomes of using the customized version of the FRAM revealed challenges affecting the transition process including waitlists for geriatric units, team-based care, lack of a discharge planner, financial concerns, and follow-up plans. The findings of this study could assist managers and other decision makers to improve the transition processes of frail older adults by addressing these challenges. The FRAM method employed in this study can be applied widely to identify work practices that are more or less successful, so that procedures and practices can be adapted to nudge healthcare processes towards paths that will yield better outcomes.

Opioid use at the transition to emerging adulthood: A latent class analysis of non-medical use of prescription opioids and heroin use.

BACKGROUND: Although rates of nonmedical opioid use are highest in late adolescence and emerging adulthood, efforts to understand the extent of the heterogeneity in opioid misuse during this time have been limited. The current study aimed to derive and define typologies of opioid use in high school students at the onset of emerging adulthood. METHODS: Survey responses from a statewide sample of high school students aged 18 and 19 (N = 26,223) were analyzed. Group-based comparisons between participants reporting opioid use and those not reporting opioid use were conducted. Among those reporting opioid use (n = 1,636), we conducted a latent class analysis (LCA) to identify heterogeneous subgroups of opioid users on the basis of non-medical use of prescription opioids (NMUPO) and heroin use. The resulting classes were then compared across various risk and protective factors using multinominal logistic regression. RESULTS: Consistent differences were observed between participants using opioids and participants not using opioids, with moderate to large effect sizes. Results from LCA revealed three subclasses: NMUPO-Any Use, NMUPO To Get High, and Heroin Use. Subclass differences were observed for non-opioid substance use, mental health, and demographics. CONCLUSIONS: Findings from this study underscore the variability of youth who engage in opioid use in late adolescence. Results also indicate that opioid use during adolescence is likely indicative of a broader set of substance use and mental health issues.

The functional resonance analysis method as a health care research methodology: a scoping review protocol.

OBJECTIVE: The objective of this review is to examine and map the literature on the use of the functional resonance analysis method in health care research. INTRODUCTION: Health care systems are highly complex and involve interrelated functions, organizations, individuals, and technologies. Understanding how these elements interact and impact health care processes is difficult because of inherent contextual and human variables. The functional resonance analysis method offers an approach to deconstruct complex systems and examine relationships between individual processes and elements. By using the functional resonance analysis method, researchers can map health care processes and uncover performance variables that can emerge and strengthen, or compromise, intended outcomes. Insight into how the functional resonance analysis method has been operationalized in health care research will help researchers and policy makers understand how the method can be used to strengthen health care systems. INCLUSION CRITERIA: The scoping review will consider research and narrative reports on the application of the functional resonance analysis method in health care research. The concepts of interest are the research questions/aims/objectives, methods used to operationalize the functional resonance analysis method, key concepts and definitions of the functional resonance analysis method, and key findings. Studies that used the functional resonance analysis method in any health care setting will be considered. METHODS: The scoping review will aim to locate published and unpublished literature by employing a three-step search strategy. Only papers published in English will be considered and no limits will be placed on the year of publication. Data extracted will include key concepts and definitions of the functional resonance analysis method, research questions/aims/objectives, methods used to operationalize the functional resonance analysis method, and key findings. Extracted data will be reported in tabular form and presented narratively to express the review question.

Age-related gene expression changes in lumbar spinal cord: Implications for neuropathic pain.

Clinically, pain has an uneven incidence throughout lifespan and impacts more on the elderly. In contrast, preclinical models of pathological pain have typically used juvenile or young adult animals to highlight the involvement of glial populations, proinflammatory cytokines, and chemokines in the onset and maintenance of pathological signalling in the spinal dorsal horn. The potential impact of this mismatch is also complicated by the growing appreciation that the aged central nervous system exists in a state of chronic inflammation because of enhanced proinflammatory cytokine/chemokine signalling and glial activation. To address this issue, we investigated the impact of aging on the expression of genes that have been associated with neuropathic pain, glial signalling, neurotransmission and neuroinflammation. We used qRT-PCR to quantify gene expression and focussed on the dorsal horn of the spinal cord as this is an important perturbation site in neuropathic pain. To control for global vs region-specific age-related changes in gene expression, the ventral half of the spinal cord was examined. Our results show that expression of proinflammatory chemokines, pattern recognition receptors, and neurotransmitter system components was significantly altered in aged (24-32 months) versus young mice (2-4 months). Notably, the magnitude and direction of these changes were spinal-cord region dependent. For example, expression of the chemokine, Cxcl13, increased 119-fold in dorsal spinal cord, but only 2-fold in the ventral spinal cord of old versus young mice. Therefore, we propose the dorsal spinal cord of old animals is subject to region-specific alterations that prime circuits for the development of pathological pain, potentially in the absence of the peripheral triggers normally associated with these conditions.