A collaboration between adult protective services and forensic accounting examiners to investigate complex financial exploitation: formative evaluation findings.

Financial exploitation (FE) is one of the most common reports to Adult Protective Services (APS) and the cases are often complex. Consequently, APS caseworkers report FE investigations to be among the most difficult while simultaneously reporting low confidence in productive outcomes for these investigations. This necessitates finding ways to support APS FE investigations. This paper describes the structure, process, and formative findings of a collaboration between forensic accounting examiners and APS workers to investigate complex cases of FE. Among the 77 FE cases completed, forensic examiners reviewed multiple years of financial records which included over 101,000 transactions, totaling over $213,000,000.00 in finances, and identified over $8,000,000 in questionable activity. Scores on the 8-item Client Satisfaction Questionnaire were high indicating high program satisfaction by APS workers, subject matter experts, and forensic examiners. These findings support the feasibility and acceptability of forensic accounting and APS collaborations to investigate complex cases of FE.

Acceptability of a real-time notification of stress and access to self-help therapies among law enforcement officers.

BACKGROUND: Law enforcement officers (LEOs) are exposed to chronic stress throughout the course of their shift, which increases the risk of adverse events. Although there have been studies targeting LEO safety through enhanced training or expanded equipment provisions, there has been little attempt to leverage personal technology in the field to provide real-time notification of LEO stress. This study tests the acceptability of implementing of a brief, smart watch intervention to alleviate stress among LEOs. METHODS: We assigned smart watches to 22 patrol LEOs across two police departments: one suburban department and one large, urban department. At baseline, we measured participants' resting heart rates (RHR), activated their watches, and educated them on brief wellness interventions in the field. LEOs were instructed to wear the watch during the entirety of their shift for 30 calendar days. When LEO's heart rate or stress continuum reached the predetermined threshold for more than 10 min, the watch notified LEOs, in real time, of two stress reduction interventions: [1] a 1-min, guided breathing exercise; and [2] A Calm app, which provided a mix of guided meditations and mindfulness exercises for LEOs needing a longer decompression period. After the study period, participants were invited for semi-structured interviews to elucidate intervention components. Qualitative data were analyzed using an immersion-crystallization approach. RESULTS: LEOs reported three particularly useful intervention components: 1) a vibration notification when hearts rates remained high, although receipt of a notification was highly variable; 2) visualization of their heart rate and stress continuum in real time; and, 3) breathing exercises. The most frequently reported type of call for service when the watch vibrated was when a weapon was involved or when a LEO was in pursuit of a murder suspect/hostage. LEOs also recollected that their watch vibrated while reading dispatch notes or while on their way to work. CONCLUSIONS: A smart watch can deliver access to brief wellness interventions in the field in a manner that is both feasible and acceptable to LEOs.

Nano-scale morphology of cardiomyocyte t-tubule/sarcoplasmic reticulum junctions revealed by ultra-rapid high-pressure freezing and electron tomography.

Detailed knowledge of the ultrastructure of intracellular compartments is a prerequisite for our understanding of how cells function. In cardiac muscle cells, close apposition of transverse (t)-tubule (TT) and sarcoplasmic reticulum (SR) membranes supports stable high-gain excitation-contraction coupling. Here, the fine structure of this key intracellular element is examined in rabbit and mouse ventricular cardiomyocytes, using ultra-rapid high-pressure freezing (HPF, omitting aldehyde fixation) and electron microscopy. 3D electron tomograms were used to quantify the dimensions of TT, terminal cisternae of the SR, and the space between SR and TT membranes (dyadic cleft). In comparison to conventional aldehyde-based chemical sample fixation, HPF-preserved samples of both species show considerably more voluminous SR terminal cisternae, both in absolute dimensions and in terms of junctional SR to TT volume ratio. In rabbit cardiomyocytes, the average dyadic cleft surface area of HPF and chemically fixed myocytes did not differ, but cleft volume was significantly smaller in HPF samples than in conventionally fixed tissue; in murine cardiomyocytes, the dyadic cleft surface area was higher in HPF samples with no difference in cleft volume. In both species, the apposition of the TT and SR membranes in the dyad was more likely to be closer than 10 nm in HPF samples compared to CFD, presumably resulting from avoidance of sample shrinkage associated with conventional fixation techniques. Overall, we provide a note of caution regarding quantitative interpretation of chemically-fixed ultrastructures, and offer novel insight into cardiac TT and SR ultrastructure with relevance for our understanding of cardiac physiology.

Socioecological indicators of senior financial exploitation: an application of data science to 8,800 substantiated mistreatment cases.

Senior financial exploitation (FE) is prevalent and harmful. Its often insidious nature and co-occurrence with other forms of mistreatment make detection and substantiation challenging. A secondary data analysis of N = 8,800 Adult Protective Services substantiated senior mistreatment cases, using machine learning algorithms, was conducted to determine when pure FE versus hybrid FE was occurring. FE represented N = 2514 (29%) of the cases with 78% being pure FE. Victim suicidal ideation and threatening behaviors, injuries, drug paraphernalia, contentious relationships, caregiver stress, and burnout and victims needing assistance were most important for differentiating FE vs non-FE-related mistreatment. The inability to afford housing, medications, food, and medical care as well as victims suffering from intellectual disability disorder(s) predicted hybrid FE. This study distinguishes socioecological factors strongly associated with the presence of FE during protective service investigations. These findings support existing and new indicators of FE and could inform protective service investigation practices.

Follistatin-based ligand trap ACE-083 induces localized hypertrophy of skeletal muscle with functional improvement in models of neuromuscular disease.

Skeletal muscle is under inhibitory homeostatic regulation by multiple ligands of the transforming growth factor-ß (TGFß) superfamily. Follistatin is a secreted protein that promotes muscle growth and function by sequestering these ligands extracellularly. In the present study, we evaluated the potential of ACE-083 - a locally acting, follistatin-based fusion protein - as a novel therapeutic agent for focal or asymmetric myopathies. Characterization of ACE-083 in vitro revealed its high affinity for heparin and extracellular matrix while surface plasmon resonance and cell-based assays confirmed that ACE-083 binds and potently neutralizes myostatin, activin A, activin B and growth differentiation factor 11 (GDF11). Intramuscular administration of ACE-083 caused localized, dose-dependent hypertrophy of the injected muscle in wild-type mice and mouse models of Charcot-Marie-Tooth disease (CMT) and Duchenne muscular dystrophy, with no evidence of systemic muscle effects or endocrine perturbation. Importantly, ACE-083 also increased the force of isometric contraction in situ by the injected tibialis anterior muscle in wild-type mice and disease models and increased ankle dorsiflexion torque in CMT mice. Our results demonstrate the potential of ACE-083 as a therapeutic agent for patients with CMT, muscular dystrophy and other disorders with focal or asymmetric muscle atrophy or weakness.

Is Interpersonal Abuse Associated with Sexual (Dis)satisfaction among Postmenopausal Women?

PURPOSE: To investigate associations between past-year verbal and/or physical abuse (VA/PA) and sexual (dis)satisfaction, that is, global or frequency-related (dis)satisfactions with sexual activity, among postmenopausal women in the Women's Health Initiative. PROCEDURES: A cross-sectional analysis of archival data was performed from the subset of 83,329 Women's Health Initiative participants (clinical trial and/or observational study components) who reported sexual activity in the year before baseline. Associations between VA/PA and global frequency (dis)satisfactions were modeled using logistic regression. MAIN FINDINGS: Most participants reported sexual satisfaction (global, 77%; frequency related, 66%). Disappointment with sexual frequency, specifically a desire for more frequent sex, was the most common dissatisfaction expressed. Past-year VA/PA exposure was reported by 9,410 participants (11%). In regression models adjusted for sociodemographic, health and health risk, and menopausal symptom variables, VA/PA was associated with higher rates of global (35% VA/PA exposed vs. 22% non-exposed; adjusted odds ratio, 1.66; 95% confidence interval, 1.53-1.80) and frequency-related dissatisfactions (50% of VA/PA exposed vs. 32% of non-exposed; adjusted odds ratio, 1.73; 95% confidence interval, 1.57-1.90). CONCLUSIONS: Sexual satisfaction was common, but not universally reported by study participants. Sexual dissatisfactions were overrepresented in VA/PA-exposed participants and associated with a desire for more frequent sexual activity. Opportunities for postmenopausal women to receive clinician-led education about safe and healthy ways to increase sexual activity are needed. Further research on this topic, particularly efforts to characterize safety concerns as well as modifiable barriers to satisfying sexual activity among postmenopausal women with recent VA/PA, would ensure that these interventions are evidence based.

Does military veteran status and deployment history impact officer involved shootings? A case-control study.

BACKGROUND: Despite veterans' preference hiring policies by law enforcement agencies, no studies have examined the nature or effects of military service or deployments on health outcomes. This study will examine the effect of military veteran status and deployment history on law enforcement officer (LEO)-involved shootings. METHODS: Ten years of data were extracted from Dallas Police Department records. LEOs who were involved in a shooting in the past 10 years were frequency matched on sex to LEOs never involved in a shooting. Military discharge records were examined to quantify veteran status and deployment(s). Multivariable logistic regression was used to estimate the effect of veteran status and deployment history on officer-involved shooting involvement. RESULTS: Records were abstracted for 516 officers. In the adjusted models, veteran LEOs who were not deployed were significantly more likely to be involved in a shooting than non-veteran officers. Veterans with a deployment history were 2.9 times more likely to be in a shooting than non-veteran officers. CONCLUSIONS: Military veteran status, regardless of deployment history, is associated with increased odds of shootings among LEOs. Future studies should identify mechanisms that explain this relationship, and whether officers who experienced firsthand combat exposure experience greater odds of shooting involvement.

Alcohol retail sales licenses and sexually transmitted infections in Texas counties, 2008-2015.

BACKGROUND: Research suggests that reduced retail alcohol outlet density may be associated with lower prevalence of HIV and other sexually transmitted infections (STIs). On-premise sale of alcohol for immediate consumption is theorized as increasing social interactions that can lead to sexual encounters. OBJECTIVE: We examined associations between on- and off-premise retail alcohol sales licenses and number of newly diagnosed HIV and STI cases in Texas counties. METHODS: Retail alcohol sales license data were obtained from the Texas Alcoholic Beverage Commission. HIV and bacterial STI data were obtained from the Texas Department of State Health Services. Associations between retail alcohol sales licenses and STIs were estimated using spatial linear models and Poisson mixed effects models for over-dispersed count data. RESULTS: Adjusting for county-specific confounders, there was no evidence of residual spatial correlation. In Poisson models, each additional on-premise (e.g., bar and restaurant) alcohol license per 10,000 population in a county was associated with a 1.5% increase (95% CI: 0.4%, 2.6%) in the rate of HIV and a 2.4% increase (95% CI: 1.9%, 3.0%) in the rate of bacterial STIs, adjusting for potential confounders. In contrast, number of off-premise licenses (e.g., take-out stores) was inversely associated with the incidence of STI and HIV, although the association with HIV was not statistically significant. CONCLUSIONS: This study adds to the limited literature on the association between retail alcohol availability and STIs. Additional research is needed on the role of alcohol availability (and policies affecting availability) in the spread of HIV and other STIs.

Factors Associated with Self-Estimated Breath Alcohol Concentration Among Bar Patrons.

BACKGROUND: Few studies have examined the context in which drinkers underestimate their breath alcohol concentration (BrAC) in natural drinking environments. This study examined factors associated with bar patrons' self-estimated BrAC in high-risk college town settings. METHODS: Guided interview and BrAC data were collected from 510 participants recruited as they exited bars located close to large universities: 1 in Florida and 1 in Texas. RESULTS: Participants with the highest measured BrACs underestimated their BrAC levels the most. Findings from multivariable linear regression analysis indicated that BrAC (std ß = 0.014, p < 0.001), number of alcoholic drinks consumed (std ß = 0.006, p < 0.01), and perceived drunkenness (std ß = 0.024, p < 0.001) had significant positive associations with BrAC self-estimates, where the regression coefficients were scaled by values approximately equal to each variable's interquartile range. Among the 321 participants with BrAC levels ≥ 0.08 g/dl, 21.2% believed their BrAC was below the legal per se driving limit of 0.08 g/dl. Results from a logistic regression analysis indicated that higher levels of perceived drunkenness were associated with better self-recognition that one's BrAC level exceeded the legal driving threshold (OR = 3.312, p < 0.001). Further, participants under 26 years of age had reduced odds of recognizing that their BrAC was greater than 0.079 g/dl (OR = 0.245, p < 0.05). CONCLUSIONS: These findings highlight the inaccuracy of self-estimated BrAC when drinking, particularly among younger drinkers. Adjusting for BrAC, situational factors were strongly associated with self-estimated BrAC. Future research is needed to better understand how altering drinking environments may improve accuracy of BrAC self-estimates and deter driving after drinking.

Barriers in detecting elder abuse among emergency medical technicians.

BACKGROUND: Elder abuse and neglect are highly under-reported in the United States. This may be partially attributed to low incidence of reporting among emergency medical technicians' (EMTs), despite state-mandated reporting of suspected elder abuse. Innovative solutions are needed to address under-reporting. The objective was to describe EMTs' experience detecting and reporting elder abuse. METHODS: Qualitative data were collected from 11 EMTs and 12 Adult Protective Services (APS) caseworkers that participated in one of five semi-structured focus groups. Focus group data were iteratively coded by two coders. RESULTS: Findings suggest a number of barriers prevent EMTs from reporting elder abuse to APS. Participants suggested that limited training on elder abuse detection or reporting has been provided to them. EMTs suggested that training, creation of an automated reporting system or brief screening tool could be used to enhance EMT's ability to detect and communicate suspected cases of elder abuse to APS. CONCLUSIONS: Results from the present study suggest that EMTs may be uniquely situated to serve as elder abuse and neglect surveillance personnel. EMTs are eager to work with APS to address the under-reporting of elder abuse and neglect, but training is minimal and current reporting procedures are time-prohibitive given their primary role as emergency healthcare providers. Future studies should seek to translate these findings into practice by identifying specific indicators predictive of elder abuse and neglect for inclusion on an automated reporting instrument for EMTs.

Towards the development of a screening tool to enhance the detection of elder abuse and neglect by emergency medical technicians (EMTs): a qualitative study.

BACKGROUND: To develop a screening tool to enhance elder abuse and neglect detection and reporting rates among emergency medical technicians (EMTs). Our primary aim was to identify the most salient indicators of elder abuse and neglect for potential inclusion on a screening tool. We also sought to identify practical elements of the tool that would optimize EMT uptake and use in the field, such as format, length and number of items, and types of response options available. METHODS: Qualitative data were collected from 23 EMTs and Adult Protective Services (APS) caseworkers that participated in one of five semi-structured focus groups. Focus group data were iteratively coded by two coders using inductive thematic identification and data reduction. Findings were subject to interpretation by the research team. RESULTS: EMTs and APS caseworks identified eight domains of items that might be included on a screening tool: (1) exterior home condition; (2) interior living conditions; (3) social support; (4) medical history; (5) caregiving quality; (6) physical condition of the older adult; (7) older adult's behavior; and, (8) EMTs instincts. The screening tool should be based on observable cues in the physical or social environment, be very brief, easily integrated into electronic charting systems, and provide a decision rule for reporting guidance to optimize utility for EMTs in the field. CONCLUSIONS: We described characteristics of a screening tool for EMTs to enhance detection and reporting of elder abuse and neglect to APS. Future research should narrow identified items and evaluate how these domains positively predict confirmed cases of elder abuse and neglect.

The cross-sectional association between severity of non-cognitive disability and self-reported worsening memory.

BACKGROUND: Research has demonstrated a clear association between cognitive decline and non-cognitive disability; however, all of these studies focus on disability as a correlate or result of some level of cognitive impairment or dysfunction. The relationship between disability and cognition is likely a complex one, that is currently incompletely described in the literature. OBJECTIVES: Our objective was to estimate the prevalence of long-term, non-cognitive disability using a population-representative sample of adults aged 18 and older, and then estimate the association between long-term, non-cognitive disability and self-reported worsening memory. METHODS: Using the 2009 Florida Behavioral Risk Factor Surveillance System (BRFSS), we measured the relationship between non-cognitive disability and worsening memory using multivariable logistic regression analysis weighted to account for the complex sampling design of the BRFSS. We also estimated the adjusted odds of worsening memory by disability severity, classified according to the types of assistance needed. RESULTS: Approximately 18% (95% confidence interval = (16%, 19%)) of Floridians were living with a long-term, non-cognitive disability in 2009. Among adults with no disability during or prior to the last year, only 5% reported worsening memory. The proportion of Floridians reporting worsening memory increases with increasing severity of disability-related limitations. In a multivariable logistic regression model, odds of worsening memory increased significantly with severity of disability-related limitations. CONCLUSIONS: These results highlight the association between non-cognitive disability and subsequent increased odds of worsening memory, independent of several other known risk factors, and a dose-response association with disability-related limitations.

Cross-sectional and longitudinal risk of physical impairment in a cohort of postmenopausal women who experience physical and verbal abuse.

BACKGROUND: Exposure to interpersonal violence, namely verbal and physical abuse, is a highly prevalent threat to women's health and well-being. Among older, post-menopausal women, several researchers have characterized a possible bi-directional relationship of abuse exposure and diminished physical functioning. However, studies that prospectively examine the relationship between interpersonal abuse exposure and physical functioning across multiple years of observation are lacking. To address this literature gap, we prospectively evaluate the association between abuse exposure and physical functioning in a large, national cohort of post-menopausal women across 12 years of follow-up observation. METHODS: Multivariable logistic regression was used to measure the adjusted association between experiencing abuse and physical function score at baseline in 154,902 Women's Health Initiative (WHI) participants. Multilevel modeling, where the trajectories of decline in physical function were modeled as a function of time-varying abuse exposure, was used to evaluate the contribution of abuse to trajectories of physical function scores over time. RESULT: Abuse was prevalent among WHI participants, with 11 % of our study population reporting baseline exposure. Verbal abuse was the most commonly reported abuse type (10 %), followed by combined physical and verbal abuse (1 %), followed by physical abuse in the absence of verbal abuse (0.2 %). Abuse exposure (all types) was associated with diminished physical functioning, with women exposed to combined physical and verbal abuse presenting baseline physical functioning scores consistent with non-abused women 20 years senior. Results did not reveal a differential rate of decline over time in physical functioning based on abuse exposure. CONCLUSIONS: Taken together, our findings suggest a need for increased awareness of the prevalence of abuse exposure among postmenopausal women; they also underscore the importance of clinician's vigilance in their efforts toward the prevention, early detection and effective intervention with abuse exposure, including verbal abuse exposure, in post-menopausal women. Given our findings related to abuse exposure and women's diminished physical functioning at WHI baseline, our work illuminates a need for further study, particularly the investigation of this association in younger, pre-menopausal women so that the temporal ordering if this relationship may be better understood.

Control of sarcoplasmic reticulum Ca2+ release by stochastic RyR gating within a 3D model of the cardiac dyad and importance of induction decay for CICR termination.

The factors responsible for the regulation of regenerative calcium-induced calcium release (CICR) during Ca(2+) spark evolution remain unclear. Cardiac ryanodine receptor (RyR) gating in rats and sheep was recorded at physiological Ca(2+), Mg(2+), and ATP levels and incorporated into a 3D model of the cardiac dyad, which reproduced the time course of Ca(2+) sparks, Ca(2+) blinks, and Ca(2+) spark restitution. The termination of CICR by induction decay in the model principally arose from the steep Ca(2+) dependence of RyR closed time, with the measured sarcoplasmic reticulum (SR) lumen Ca(2+) dependence of RyR gating making almost no contribution. The start of CICR termination was strongly dependent on the extent of local depletion of junctional SR Ca(2+), as well as the time course of local Ca(2+) gradients within the junctional space. Reducing the dimensions of the dyad junction reduced Ca(2+) spark amplitude by reducing the strength of regenerative feedback within CICR. A refractory period for Ca(2+) spark initiation and subsequent Ca(2+) spark amplitude restitution arose from 1), the extent to which the regenerative phase of CICR can be supported by the partially depleted junctional SR, and 2), the availability of releasable Ca(2+) in the junctional SR. The physical organization of RyRs within the junctional space had minimal effects on Ca(2+) spark amplitude when more than nine RyRs were present. Spark amplitude had a nonlinear dependence on RyR single-channel Ca(2+) flux, and was approximately halved by reducing the flux from 0.6 to 0.2 pA. Although rat and sheep RyRs had quite different Ca(2+) sensitivities, Ca(2+) spark amplitude was hardly affected. This suggests that moderate changes in RyR gating by second-messenger systems will principally alter the spatiotemporal properties of SR release, with smaller effects on the amount released.

Termination of calcium-induced calcium release by induction decay: an emergent property of stochastic channel gating and molecular scale architecture.

Calcium-induced calcium release (CICR) is an inherently regenerative process due to the Ca(2+)-dependent gating of ryanodine receptors (RyRs) in the sarco/endoplasmic reticulum (SR) and is critical for cardiac excitation-contraction coupling. This process is seen as Ca(2+) sparks, which reflect the concerted gating of groups of RyRs in the dyad, a specialised junctional signalling domain between the SR and surface membrane. However, the mechanism(s) responsible for the termination of regenerative CICR during the evolution of Ca(2+) sparks remain uncertain. Rat cardiac RyR gating was recorded at physiological Ca(2+), Mg(2+) and ATP levels and incorporated into a 3D model of the cardiac dyad which reproduced the time-course of Ca(2+) sparks, Ca(2+) blinks and Ca(2+) spark restitution. Model CICR termination was robust, relatively insensitive to the number of dyadic RyRs and automatic. This emergent behaviour arose from the rapid development and dissolution of nanoscopic Ca(2+) gradients within the dyad. These simulations show that CICR does not require intrinsic inactivation or SR calcium sensing mechanisms for stability and cessation of regeneration that arises from local control at the molecular scale via a process we call 'induction decay'.

Local control in cardiac E-C coupling.

The development of local control theories in cardiac excitation-contraction coupling solved a major problem in the calcium-induced calcium release (CICR) hypothesis. Local control explained how regeneration, inherent in the CICR mechanism, might be limited spatially to enable graded Ca release (and force production). The key lies in the stochastic recruitment of individual calcium release units (couplons or CRUs) where adjacent CRUs are partially uncoupled by the distance between them. In the CRU, individual groups of sarcoplasmic reticulum calcium release channels (RyRs) are very close to the surface membrane where calcium influx, controlled by membrane depolarization, leads to high local Ca levels that enable a high speed response from RyRs that have a very low probability to opening at resting Ca levels. However, calcium diffusion from an activated CRU results in adjacent CRUs being exposed to much lower levels of Ca and probability of activation. This effectively uncouples the CRUs and limits overall regenerative gain to enable stability without compromising sensitivity. Nevertheless, it is still unclear how the CRU terminates its release of calcium on the physiological timescale, and possible mechanisms (and problems) are briefly reviewed. We suggest that modulation in RyR gating may serve to control average SR Ca levels to regulate other metabolic functions of the sarco(endo)plasmic reticulum beyond regulating contractility. This article is part of a special issue entitled "Local Signaling in Myocytes."

Effect of changes in action potential spike configuration, junctional sarcoplasmic reticulum micro-architecture and altered t-tubule structure in human heart failure.

Using a Monte-Carlo model of L-type Ca2+ channel (DHPR) gating, we have examined the effect of changes in the early time course of the action potential as seen in human heart failure on excitation contraction coupling. The time course of DHPR Ca2+ influx was coupled into a simple model of sarcoplasmic reticulum Ca2+ release. Our model shows that the loss of the initial spike in human heart failure should reduce the synchrony of Ca2+ spark production and lead to the appearance of late Ca2+ sparks and greater non-uniformity of intracellular Ca2+. Within the junctional space of the cardiac dyad, a small increase in the mean distance of a DHPR from a RyR results in a marked decrease in the ability of the DHPR-mediated increase in local [Ca2+] concentration to activate RyRs. This suggests that the efficiency of EC coupling may be reduced if changes in micro-architecture develop and such effects have been noted in experimental models of heart failure. High resolution imaging of t-tubules in tachycardia-induced heart failure show deranged t-tubule structure. While in normal human hearts t-tubules run mainly in a radial direction, t-tubules in the heart failure samples were oriented more toward the long axis of the cell. In addition, t-tubules may become dilated and bifurcated. Our data suggest that changes in the micro-architecture of the cell and membrane structures associated with excitation-contraction coupling, combined with changes in early action potential configuration can reduce the efficiency by which Ca2+ influx via DHPRs can activate SR calcium release and cardiac contraction. While the underlying cause of these effects is unclear, our data suggest that geometric factors can play an important role in the pathophysilogy of the human heart in failure.

Differential expression of ryanodine receptors in the rat cochlea.

This study examined the localization and functional expression of ryanodine receptors (RyR) within the cochlea using a combination of reverse transcription-polymerase chain reaction, immunolabeling techniques, and confocal Ca2+ imaging. All three RyR isoform mRNA transcripts were detected in the adult rat cochlea. Immunoperoxidase and immunofluorescence labeling showed that the three isoforms were differentially expressed. The most pronounced RyR protein expression, involving all three isoforms, occurred in the cell bodies of the spiral ganglion neurons. RyR3 labeling extended to the synaptic terminals innervating the inner and outer hair cells. RyR2 expression also occurred in the inner hair cells and supporting cells of the organ of Corti, while cells associated with ion homeostasis in the cochlea, such as the interdental cells of the spiral limbus (RyR1), and the epithelial cells of the spiral prominence and basal cells of the stria vascularis (RyR2 and RyR3), were also immunopositive. The functionality of RyR-gated Ca2+ stores in the spiral ganglion neurons was shown by confocal calcium imaging of fluo-4 fluorescence in rat cochlear slices. Caffeine (5 mM) evoked an increase in intracellular Ca2+ concentration in the cell bodies of the spiral ganglion neurons which occurred inthe absence of external Ca2+. Ryanodine (50 nm-1 microM) evoked comparable increases in intracellular Ca2+ concentration. These findings suggest that RyR-mediated Ca2+ release may be involved in auditory neurotransmission, sound transduction, and cochlear electrochemical homeostasis.

Long-term effects of fire frequency on carbon storage and productivity of boreal forests: a modeling study.

Climate change is predicted to shorten the fire interval in boreal forests. Many studies have recorded positive effects of fire on forest growth over a few decades, but few have modeled the long-term effects of the loss of carbon and nitrogen to the atmosphere. We used a process-based, dynamic, forest ecosystem model, which couples the carbon, nitrogen and water cycles, to simulate the effects of fire frequency on coniferous forests in the climate of Prince Albert, Saskatchewan. The model was calibrated to simulate observed forest properties. The model predicted rapid short-term recovery of net primary productivity (NPP) after fire, but in the long term, supported the hypotheses that (1) current NPP and carbon content of boreal forests are lower than they would be without periodic fire, and (2) any increase in fire frequency in the future will tend to lower NPP and carbon storage. Lower long-term NPP and carbon storage were attributable to (1) loss of carbon on combustion, equal to about 20% of NPP over a 100-200 year fire cycle, (2) loss of nitrogen by volatilization in fire, equal to about 3-4 kg N ha(-1) year(-1) over a 100-200 year fire cycle, and (3) the fact that the normal fire cycle is much shorter than the time taken for the forest (especially the soil) to reach an equilibrium carbon and nitrogen content. It was estimated that a shift in fire frequency from 200 to 100 years over 1000 Mha of boreal forest would release an average of about 0.1 Gt C year(-1) over many centuries.