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- Автор: Gajas
The implementation strategies were not specified well enough. Future studies should prioritize implementation at scale, target higher levels health systems meso and macro levels , and test sustainability of NCD programs. They should employ designs with stronger internal validity, be more conceptually driven, and use mixed methods to understand mechanisms.
To maximize impact of the research under limited resources, adding implementation science outcomes to effectiveness research and regional collaborations are promising. Author summary Why was the study done?
While the evidence for the clinical effectiveness of most noncommunicable disease NCD prevention and treatment interventions is well established, care delivery models and means of scaling these up to entire populations in need in heterogeneous and resource-constrained health systems are not. This can promote faster, more efficient, and more effective scale-up of life-saving and health-preserving health system strategies.
Evidence needed on the current state of implementation research on World Health Organization WHO priority NCD prevention and control interventions to help inform research priority. What did the researchers do and find? Reviewed studies emphasized a few health areas, such as cervical cancer, with many other high-burden conditions little researched. The majority of studies were proof of concept or pilot, quantitative using weaker study designs and targeted the micro level of health system.
What do these findings mean? While implementation research on priority NCDs has grown substantially, from under 10 studies per year in early s to 51 studies in , this is still vastly incommensurate with the health burden of NCDs. PLoS Med 19 7 : e This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Data Availability: All relevant data are within the manuscript and its supporting information files. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. RM and RS are employed by the study funders. Cardiovascular diseases are the leading causes of NCD mortality, followed by cancers, respiratory diseases, and diabetes [ 1 ]. Risk factors such as tobacco and alcohol use, physical inactivity, and unhealthy diets result in significantly greater risk of dying from NCDs.
Primary, secondary, and tertiary prevention strategies are vital in addressing NCD burden [ 1 ]. Recent analysis shows that no LMIC is on track to meet this target for both men and women if they maintain their to average rates of decline [ 3 ]. NCD prevention and control should not be regarded as a vertical issue separated from other health conditions. This article is intended to serve as an introduction to this project and to provide details for investigators who may be seeking to replicate or extend these methods for other related research endeavors.
The onset of depression during adolescence is known to adversely affect the course and prognosis of the disorder. Adolescent-onset depression is associated with longer, more severe, and more recurrent depressive episodes that are often refractory to treatment Dunn and Goodyer, ; Fergusson et al.
Because adolescence is a period of significant neurodevelopment, the adverse impact of depression on ongoing brain maturation may explain, in part, why adolescent-onset depression is associated with more severe symptoms and a higher likelihood of recurrence than is adult-onset depression Naicker et al.
Adolescence is a period characterized by major life transitions and heightened stress; stress is a frequent precipitant of MDD, a contributor to the course and maintenance of depressive symptoms, and a driver of neuroplasticity Hammen, ; Ho, Moreover, depression itself is a stressful experience that may affect neurodevelopment through various psychobiological pathways.
However, despite the consensus that stress affects neurodevelopmental processes McEwen, ; Nelson and Gabard-Durnam, , and that neurodevelopmental processes should be considered explicitly in models of adolescent MDD Cicchetti and Rogosch, ; Lichenstein et al. Addressing this gap in knowledge requires research that takes a longitudinal approach to characterizing trajectories of brain development and depressive symptoms Gotlib and Ordaz, In addition to the scarcity of longitudinal neuroimaging data on this topic, another major factor that limits our understanding of these processes is the lack of comprehensive integration of information across different modalities and neurobiological systems that are relevant to the study of adolescent stress, neurodevelopment, and depression.
Investigators have posited that inflammatory processes are critical in understanding how stress affects neurodevelopment in the context of depression Miller et al. It is well recognized that life stress activates the immune system by initiating a cascade of inflammatory responses, including increased production of pro-inflammatory cytokines in the peripheral nervous system Miller et al.
Critically, peripheral cytokines can cross the blood-brain barrier and alter its permeability Banks et al. Specifically, inflammatory cytokines activate the enzyme indoleamine-2,3 dioxygenase, which converts tryptophan a precursor to serotonin to kynurenine Guillemin et al.
Thus, glutamatergic excitotoxicity through the kynurenine pathway and related pathways may be a key mechanism by which stress leads to the neurophenotypes commonly identified in depression, including gray matter loss as measured by smaller limbic volumes, cortical thinning, and lower surface area , lower integrity of white matter microstructure in fronto-cingulate-limbic tracts Aghajani et al. While neuroinflammation and mediators of the immune response in the central nervous system, such as microglia, cannot currently be measured non-invasively, technologies such as proton magnetic resonance spectroscopy 1H-MRS can be used to measure non-invasively the downstream effects of inflammation on neurotransmitter levels, including glutamate.
Interestingly, these findings stand in contrast to the work reviewed above, which have consistently found elevated levels of Glu in response to stress and higher levels of Glu contributing to neurotoxicity Miller et al. Given that the vast majority It is also important to note that with the exception of the study by Gabbay et al. Indeed, no study to date has examined inflammation and its effects on glutamate levels and neurodevelopmental trajectories in adolescents with depression.
Addressing this gap will help to elucidate whether 1 elevated inflammation and glutamate are already present in depressed adolescents or, alternatively, are consequences of chronic depression, as has been seen in adults with treatment-resistant depression; and 2 higher levels of inflammation and glutamate affect adolescent neurodevelopment in ways that increase risk for the development of subsequent episodes of depression.
Moreover, researchers have posited that antioxidants, including glutathione and ascorbate, buffer against the neurotoxic effects of excessive glutamate in neurons, and may serve a neuroprotective role against glutamatergic excitotoxicity Ballaz et al. That is, antioxidants may attenuate the effects of inflammation on glutamate, as well as the effects of inflammation-related glutamatergic neurotoxicity on neurodevelopment and depressive symptoms; these formulations, however, have not yet been tested.
We are using multimodal imaging to comprehensively assess neurophenotypes of depressive disorders and integrating information across traditionally disparate yet empirically relevant neurobiological systems i. Specifically, we are testing the central hypothesis that glutamate mediates the links between inflammation and the developmental trajectories of ACC connectivity over 18 months.
We focused our investigation on the ACC because it is a large integrative region that spans multiple networks implicated in depression — including the salience network, the default mode network, and the central executive network — and subserves a host of functions commonly disrupted in depression, including emotion generative and regulatory processing, reward encoding, threat detection, learning, and error monitoring Botvinick et al.
Critically, the ACC undergoes significant maturation during adolescence Power et al. Conceptual model and study aims. Green arrows indicate moderation of associations. Finally, we are also recruiting a sample of psychiatrically healthy adolescents in order to examine the possibility that deviations from normative levels or trajectories in these neurobiological markers characterize adolescent depression.
Participants will be recruited using flyers; advertisements on Craigslist, Nextdoor, and Facebook; and an internal referral program. Design and Procedures The study will take place over an month period, with three in-person laboratory sessions for all participants, approximately 9 months apart.
Each timepoint T1, T2, T3 will consist of two in-person visits V1, V2 that will occur within 3 weeks of one another. Once an adolescent is confirmed to be eligible, the participant will be invited to attend the second lab session V2. V2 will include the MRI brain scan and a finger prick blood sample. These procedures will be repeated at T2 and T3. Between each of the three time points, participants will be asked to complete three surveys 2 online and 1 via phone call from home every other month e.
See Figure 3 for more details. Longitudinal study protocol. TIGER is a longitudinal study approximately months long with 3 timepoints, approximately 9 months apart. Each timepoint will include two laboratory visits Visit 1 and Visit 2. Please also see Table 1 for a list of measures collected within each session visit at each timepoint.
Clinical and Behavioral Measures Demographics Participant age, sex assigned at birth, gender identity, sexual orientation, ethnicity, and race will be obtained through self-report questionnaires, while family socioeconomic status income range and highest education of parent will be obtained through parent-report.
Family History To capture family history of psychiatric disorders, with a focus on mood disorders and suicide, in all first-degree blood-relatives of the participant, we will administer a modified version of the Family Interview for Genetic Studies FIGS Gershon et al. If any endorsements of a down or elevated mood are made, the interviewer will continue into a screener probing for DSM-IV symptom criteria for depressive and bipolar disorders.
A diagnosis will then be determined to be not present, suspected, or definite. Did any see any professionals for their emotions or have any medications or treatments? As in previous studies of depressed adolescents, we will use the average of the pubic hair i. Female participants will also be asked to provide information on their menstrual cycle by providing approximate dates of their first period, as well their most recent periods at each timepoint.
Participants will also be asked to report on details of their current and past use of hormone contraceptives. The decision to rely on DSM-V criteria for substance use was due to the inclusion of substance-specific withdrawal symptoms. Moreover, there is compelling evidence across adolescents and substances that criteria for abuse and dependence in the DSM-IV reflect the same underlying condition rather than distinct nosologies Hasin et al. Within each psychiatric module, ratings on a scale of 0 to 3 no information to threshold will be assigned to both the current and the most severe past episode.
Age of onset, duration of episode, and number of episodes if relevant will be assessed for each disorder, as well as any academic, social, and familial impairment. To assess whether the participant has experienced remission or recurrence of a depressive disorder at T2 and T3, we will follow procedures from the Treatment for Adolescents with Depression Study TADS Curry et al. The CDRS-R is a clinician-rated scale and one of the most widely used rating scales for assessing severity and change of depression symptoms for clinical research trials in pediatric depression Isa et al.
The CDRS-R is comprised of 17 questions, the first 14 of which are administered to both parent and adolescent participants, while the last three items are rated based on clinician observation and assess non-verbal characteristics such as depressed affect, listless speech, and hypoactivity. Interviewers will assign a total summary score integrating both parent and child interviews. Depression Self-Report Self-reported severity of symptoms will be assessed with the Reynolds Adolescent Depression Scale RADS-2 Reynolds, , a item questionnaire designed to assess severity of depressive symptoms in adolescents in both school and clinical settings Reynolds, We anticipate that data from the RADS-2 subscales will be useful for exploring hypotheses concerning subtypes of depression.
Finally, we will also administer the Patient Health Questionnaire-9 PHQ-9 , which is a nine-item questionnaire frequently used in both clinical and research settings to assess depression severity and symptom change e. We anticipate that data from the PHQ-9 will facilitate opportunities to combine our data with other studies across developmental populations. The MASC-2 has high convergent validity, both strong inter-rater and test—retest reliability, and has been widely used to assess anxiety within adolescents March et al.
Suicidal Thoughts and Behaviors Clinical Interviews Because depression is one of the strongest psychiatric risk factors for suicidal thoughts and behaviors STBs Franklin et al. Within the depression module of the K-SADS-PL, we will assess various levels of STBs — ranging from abstract thoughts, recurrent thoughts, suicidal ideation, suicidal acts researching methods, obtaining materials, creating a plan , and suicide attempts. The C-SSRS is a semi-structured interview and has strong validity, internal consistency and high sensitivity Posner et al.
Through administration of the C-SSRS, interviewers will assess the severity of suicidal ideation and gather information regarding the frequency, duration, and controllability of thoughts; possible deterrents to acting; and reasons for ideation. Interviewers will also utilize the C-SSRS to gather information about suicidal behaviors, including details regarding actual, interrupted, or aborted attempts as well as preparatory acts such as gathering materials or writing a suicide note.
Finally, given the co-occurrence of suicidal thoughts and attempts with non-suicidal self-injurious NSSI behaviors Nock et al. The SITBI is a structured interview that assesses the history, frequency, and intensity of thoughts and behaviors related to non-suicidal self-injury. Ages of onset, as well as frequency of thoughts and behaviors in the last year or since last visit, for T2 and T3 assessments , last month, and week prior to the assessment will also be obtained.
The SITBI has high convergent validity, both strong inter-rater and test—retest reliability, and has been widely used with adolescents van Alphen et al. The SIQ-JH is a item measure designed for use with adolescents between the ages of 12—18 years, and has high internal consistency, test—retest reliability, and predictive validity Reynolds, Implicit Suicidal Ideation Cognitive Task In addition to explicit or self-disclosed methods of suicidal ideation, we will administer a computerized task to probe suicidal ideation without relying on self-report, as there may be several reasons why an adolescent may not be truthful about their thoughts surrounding death or suicide Nock et al.
The IAT has been shown to have strong reliability Cunningham et al. Importantly, we have previously demonstrated in an independent community sample of adolescents ages 9—13 years that morphological alterations in the dorsal striatum — specifically the putamen and caudate — predict IAT bias scores 2 years later Ho et al.
Interestingly, putamen and caudate volumes did not predict SIQ-JH scores, suggesting that not only are dopaminergic striatal structures implicated in suicide risk, but also that neurobiological phenotypes may be better predictors of objective markers of suicide risk.
Life Stress Given the key role of stress in our theoretical model, we will obtain comprehensive information on cumulative life stress in each participant using the Adolescent version of the Stress and Adversity Inventory STRAIN Slavich et al. The Adolescent STRAIN is a self-administered computerized set of questions probing exposure to 75 distinct stressors, including 33 acute life events and 42 chronic difficulties.
Through branching logic, additional questions are generated to assess the severity, frequency, timing, and duration of any endorsed stressor. Childhood Trauma Questionnaire Meta-analytic and epidemiological evidence has shown that maltreatment experienced during childhood is significantly associated with depression in adolescents McLaughlin et al.
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