DATAPLANE-BASED DISTRIBUTED DENIAL-OF-SERVICE (DDOS) MITIGATION AND SPOOFING PREVENTION VIA SEGMENT ROUTING OVER INTERNET PROTOCOL VERSION 6 (SRV6) NETWORK PROGRAMMING

Techniques described herein augment packet tagging Distributed Denial-of-Service (DDOS) mitigation solutions with a powerful anti-spoofing capability. A Segment Routing over Internet Protocol (IP) version 6 (SRv6) network programming technique is proposed herein wherein authenticated sessions are given an SRv6 header to append to all outbound packets. Traffic with the valid SRv6 header is allowed to pass thru the service provider network whereas all other traffic destined to the victim of the DDOS attack is dropped. The valid SRv6 header address can be rotated from amongst the 18, 446, 744, 073, 709, 551, and 616 possible addresses found in a /64 IPv6 subnet, thus making it nearly impossible to spoof the valid SRv6 address

A parent-targeted group intervention for pediatric pain delivered in-person or virtually:feasibility, acceptability, and effectiveness

OBJECTIVES: Parents play integral roles in their youth's chronic pain and can experience elevated distress related to caregiving. This study examined a cognitive-behavior therapy-based parent-targeted group intervention, including understudied/novel resilience/risk (eg, distress, parenting self-regulation), and compared the effect of in-person versus virtual delivery format. HYPOTHESES: (1) Adequate feasibility and acceptability (enrolment&gt;33%, attendance &gt;60%, attrition &lt;25%, satisfaction ratings &gt;90%), with higher indicators of feasibility in the virtual groups; (2) Significant improvements in parent psychological flexibility, protectiveness, distress, and parenting self-regulation at posttreatment that were maintained at follow-up, with no difference between delivery type. METHODS: Parents were enroled from an outpatient pediatric chronic pain clinic and participated in the group intervention in-person or virtually; questionnaires were completed at baseline, posttreatment, and 3-month follow-up. RESULTS: Enrolment (55% in-person, 65% virtual) and attendance (86% in-person, 93% virtual) were higher, and attrition was lower than expected (4% in-person, 7% virtual). Satisfaction was high (4.95/5 in-person, 4.85/5 virtual); on written feedback, parents enjoyed connecting with other parents (27/56, 48%) the most. The least preferred were the virtual format (5/36, 14%) and timing of the group (6/52, 12%). There were no differences between delivery formats in feasibility/acceptability. The intervention significantly improved parents' psychological flexibility, protectiveness, distress, and parenting self-regulation over time. A small group difference favored the in-person format for psychological flexibility, and an interaction effect for parenting self-regulation was found. DISCUSSION: This standalone parent-targeted group intervention had positive effects on parent outcomes delivered either in-person or virtually.</p

A parent-targeted group intervention for pediatric pain delivered in-person or virtually:feasibility, acceptability, and effectiveness

OBJECTIVES: Parents play integral roles in their youth's chronic pain and can experience elevated distress related to caregiving. This study examined a cognitive-behavior therapy-based parent-targeted group intervention, including understudied/novel resilience/risk (eg, distress, parenting self-regulation), and compared the effect of in-person versus virtual delivery format. HYPOTHESES: (1) Adequate feasibility and acceptability (enrolment&gt;33%, attendance &gt;60%, attrition &lt;25%, satisfaction ratings &gt;90%), with higher indicators of feasibility in the virtual groups; (2) Significant improvements in parent psychological flexibility, protectiveness, distress, and parenting self-regulation at posttreatment that were maintained at follow-up, with no difference between delivery type. METHODS: Parents were enroled from an outpatient pediatric chronic pain clinic and participated in the group intervention in-person or virtually; questionnaires were completed at baseline, posttreatment, and 3-month follow-up. RESULTS: Enrolment (55% in-person, 65% virtual) and attendance (86% in-person, 93% virtual) were higher, and attrition was lower than expected (4% in-person, 7% virtual). Satisfaction was high (4.95/5 in-person, 4.85/5 virtual); on written feedback, parents enjoyed connecting with other parents (27/56, 48%) the most. The least preferred were the virtual format (5/36, 14%) and timing of the group (6/52, 12%). There were no differences between delivery formats in feasibility/acceptability. The intervention significantly improved parents' psychological flexibility, protectiveness, distress, and parenting self-regulation over time. A small group difference favored the in-person format for psychological flexibility, and an interaction effect for parenting self-regulation was found. DISCUSSION: This standalone parent-targeted group intervention had positive effects on parent outcomes delivered either in-person or virtually.</p

Economic evaluation and decision making for quality improvement in complex community health systems

Community health is a fundamental part of many healthcare systems and is widely advocated as a means to increase access to and coverage of health services, yet the quality of care in large-scale community health programmes is mixed. Quality improvement (QI) approaches are now being tested in community settings and there is limited evidence that integrating QI approaches can underpin success of community programmes. However, how best to measure that success and the cost and value thereof to the different decision makers in complex community health systems is not yet known. This thesis provides the first economic evaluation of QI in community health systems, linking this to an exploration of decision making that includes an assessment of how economic evidence like this is used. Using an interdisciplinary mixed methods approach, I worked across several countries (Ethiopia, Kenya, Indonesia, Malawi, and Mozambique) to provide evidence to inform policy decisions. I first examined the costs of a QI intervention in all five countries and then used those data as the foundation of a cost-effectiveness decision tree model for the intervention in Kenya. Through interviews with national and global decision makers, I qualitatively examined the use and value of evidence in community health programmes. I present the results in a series of three related publications, linking them together with a literature review and discussion that show how these studies build upon each other and what they add to the existing evidence base. This thesis shows that QI for community health is a good investment contingent on an existing cadre of community health workers. The budget impact of the QI intervention is low (less than 0.53% of general government health expenditure) and the modelled cost-effectiveness yields an incremental cost-effectiveness ratio of US$249.43 per disability-adjusted life year. The absolute costs are highly dependent on context and the intensity of the intervention. Qualitative findings indicate that decision makers are not satisfied with existing evidence and have limited capacity to assess its relevance for their settings and perspectives. As a result, power and politics fill this evidence gap. Evidence must be at the heart of decisions in funding universal health coverage for them to be sustainable. To achieve this, the global community must strengthen the relevance of evidence and build the capacity of decision makers to understand and apply it. For a complex system, useful evaluation should describe context and mechanism of an intervention, estimate the effect size on both programmatic and health impacts and accurately reflect the opportunity costs

Pharmacotherapy for treatment-resistant schizophrenia

Schizophrenia is a disabling mental illness with a lifetime prevalence of 0.7% worldwide and significant, often devastating, consequences on social and occupational functioning. A range of antipsychotic medications are available; however, suboptimal therapeutic response in terms of psychotic symptoms is common and affects up to one-third of people with schizophrenia. Negative symptoms are generally less amenable to treatment. Because of the consequences of inadequate symptom control, effective treatment strategies are required for people with treatment-resistant schizophrenia. Clozapine has been shown to be more effective than other antipsychotics in treatment-resistant populations in several studies; however, the occurrence of adverse effects, some of which are potentially life-threatening, are important limitations. In addition to those who are intolerant to clozapine, only 30% to 50% experience clinically significant symptom improvement. This review describes the recent evidence for treatment strategies for people not responding to nonclozapine antipsychotic agents and people not responding or only partially responding to clozapine

A novel mode of capping protein-regulation by Twinfilin

Cellular actin assembly is controlled at the barbed ends of actin filaments, where capping protein (CP) limits polymerization. Twinfilin is a conserved in vivo binding partner of CP, yet the significance of this interaction has remained a mystery. Here, we discover that the C-terminal tail of Twinfilin harbors a CP-interacting (CPI) motif, identifying it as a novel CPI-motif protein. Twinfilin and the CPI-motif protein CARMIL have overlapping binding sites on CP. Further, Twinfilin binds competitively with CARMIL to CP, protecting CP from barbed-end displacement by CARMIL. Twinfilin also accelerates dissociation of the CP inhibitor V-1, restoring CP to an active capping state. Knockdowns of Twinfilin and CP each cause similar defects in cell morphology, and elevated Twinfilin expression rescues defects caused by CARMIL hyperactivity. Together, these observations define Twinfilin as the first \u27pro-capping\u27 ligand of CP and lead us to propose important revisions to our understanding of the CP regulatory cycle

'Do you trust those data?'-a mixed-methods study assessing the quality of data reported by community health workers in Kenya and Malawi.

High-quality data are essential to monitor and evaluate community health worker (CHW) programmes in low- and middle-income countries striving towards universal health coverage. This mixed-methods study was conducted in two purposively selected districts in Kenya (where volunteers collect data) and two in Malawi (where health surveillance assistants are a paid cadre). We calculated data verification ratios to quantify reporting consistency for selected health indicators over 3 months across 339 registers and 72 summary reports. These indicators are related to antenatal care, skilled delivery, immunization, growth monitoring and nutrition in Kenya; new cases, danger signs, drug stock-outs and under-five mortality in Malawi. We used qualitative methods to explore perceptions of data quality with 52 CHWs in Kenya, 83 CHWs in Malawi and 36 key informants. We analysed these data using a framework approach assisted by NVivo11. We found that only 15% of data were reported consistently between CHWs and their supervisors in both contexts. We found remarkable similarities in our qualitative data in Kenya and Malawi. Barriers to data quality mirrored those previously reported elsewhere including unavailability of data collection and reporting tools; inadequate training and supervision; lack of quality control mechanisms; and inadequate register completion. In addition, we found that CHWs experienced tensions at the interface between the formal health system and the communities they served, mediated by the social and cultural expectations of their role. These issues affected data quality in both contexts with reports of difficulties in negotiating gender norms leading to skipping sensitive questions when completing registers; fabrication of data; lack of trust in the data; and limited use of data for decision-making. While routine systems need strengthening, these more nuanced issues also need addressing. This is backed up by our finding of the high value placed on supportive supervision as an enabler of data quality

Somatic Symptom Disorder, Conversion Disorder, and Chronic Pain: Pediatric Clinician Perspectives

Objectives: The appropriateness and relevance of somatic symptom disorder and conversion disorder (American Psychiatric Association, 2013) diagnoses are in question as they relate to pediatric chronic pain. This survey-based study on pediatric chronic pain explores how these psychiatric diagnoses are made and perceived and how treatment of patients is approached by Canadian health care professionals working in pediatric chronic pain clinics. Method: Health care professionals (N = 50) completed the survey, which contained both qualitative and quantitative items. Results: Of participants, 88% reported moderate/advanced training in pain, whereas only 26% reported moderate/advanced training in somatic symptom disorder and conversion disorder. Somatic symptom disorder and conversion disorder were reportedly diagnosed in approximately 17% and 5% of young people with chronic pain, respectively; however, overall, the participants were not confident or only slightly confident when diagnosing these disorders. There were no major differences in the reported interventions used to treat pain, somatic symptom disorder, or conversion disorder. Conclusions: These results highlight the need for standardized training in pain and psychiatric assessment, diagnosis, and treatment; diagnostic guidelines; and how to best provide this training to health care staff who work with young people with chronic pain

Aggression, Social Stress, and the Immune System in Humans and Animal Models

Social stress can lead to the development of psychological problems ranging from exaggerated anxiety and depression to antisocial and violence-related behaviors. Increasing evidence suggests that the immune system is involved in responses to social stress in adulthood. For example, human studies show that individuals with high aggression traits display heightened inflammatory cytokine levels and dysregulated immune responses such as slower wound healing. Similar findings have been observed in patients with depression, and comorbidity of depression and aggression was correlated with stronger immune dysregulation. Therefore, dysregulation of the immune system may be one of the mediators of social stress that produces aggression and/or depression. Similar to humans, aggressive animals also show increased levels of several proinflammatory cytokines, however, unlike humans these animals are more protected from infectious organisms and have faster wound healing than animals with low aggression. On the other hand, subordinate animals that receive repeated social defeat stress have been shown to develop escalated and dysregulated immune responses such as glucocorticoid insensitivity in monocytes. In this review we synthesize the current evidence in humans, non-human primates, and rodents to show a role for the immune system in responses to social stress leading to psychiatric problems such as aggression or depression. We argue that while depression and aggression represent two fundamentally different behavioral and physiological responses to social stress, it is possible that some overlapped, as well as distinct, pattern of immune signaling may underlie both of them. We also argue the necessity of studying animal models of maladaptive aggression induced by social stress (i.e., social isolation) for understanding neuro-immune mechanism of aggression, which may be relevant to human aggression