Quantitative evidence synthesis methods for the assessment of the effectiveness of treatment sequences for clinical and economic decision-making: a review and taxonomy of simplifying assumptions

Sequential use of alternative treatments for chronic conditions represents a complex intervention pathway; previous treatment and patient characteristics affect both the choice and effectiveness of subsequent treatments. This paper critically explores the methods for quantitative evidence synthesis of the effectiveness of sequential treatment options within a health technology assessment (HTA) or similar process. It covers methods for developing summary estimates of clinical effectiveness or the clinical inputs for the cost-effectiveness assessment and can encompass any disease condition. A comprehensive review of current approaches is presented, which considers meta-analytic methods for assessing the clinical effectiveness of treatment sequences and decision-analytic modelling approaches used to evaluate the effectiveness of treatment sequences. Estimating the effectiveness of a sequence of treatments is not straightforward or trivial and is severely hampered by the limitations of the evidence base. Randomised controlled trials (RCTs) of sequences were often absent or very limited. In the absence of sufficient RCTs of whole sequences, there is no single best way to evaluate treatment sequences; however, some approaches could be re-used or adapted, sharing ideas across different disease conditions. Each has advantages and disadvantages, and is influenced by the evidence available, extent of treatment sequences (number of treatment lines or permutations), and complexity of the decision problem. Due to the scarcity of data, modelling studies applied simplifying assumptions to data on discrete treatments. A taxonomy for all possible assumptions was developed, providing a unique resource to aid the critique of existing decision-analytic models

Plasma electrons above Saturn's main rings: CAPS observations

We present observations of thermal ( similar to 0.6 - 100eV) electrons observed near Saturn's main rings during Cassini's Saturn Orbit Insertion (SOI) on 1 July 2004. We find that the intensity of electrons is broadly anticorrelated with the ring optical depth at the magnetic footprint of the field line joining the spacecraft to the rings. We see enhancements corresponding to the Cassini division and Encke gap. We suggest that some of the electrons are generated by photoemission from ring particle surfaces on the illuminated side of the rings, the far side from the spacecraft. Structure in the energy spectrum over the Cassini division and A-ring may be related to photoelectron emission followed by acceleration, or, more likely, due to photoelectron production in the ring atmosphere or ionosphere

Poor Individual Risk Classification From Adverse Childhood Experiences Screening

Introduction: Adverse childhood experiences confer an increased risk for physical and mental health problems across the population, prompting calls for routine clinical screening based on reported adverse childhood experience exposure. However, recent longitudinal research has questioned whether adverse childhood experiences can accurately identify ill health at an individual level. // Methods: Revisiting data collected for the Adverse Childhood Experience Study between 1995 and 1997, this study derived approximate area under the curve estimates to test the ability of the retrospectively reported adverse childhood experience score to discriminate between adults with and without a range of common health risk factors and disease conditions. Furthermore, the classification accuracy of a recommended clinical definition for high-risk exposure (≥4 versus 0–3 adverse childhood experiences) was evaluated on the basis of sensitivity, specificity, positive and negative predictive values, and positive likelihood ratios. // Results: Across all health outcomes, the levels of discrimination for the continuous adverse childhood experience score ranged from very poor to fair (area under the curve=0.50–0.76). The binary classification of ≥4 versus 0–3 adverse childhood experiences yielded high specificity (true-negative detection) and negative predictive values (absence of ill health among low-risk adverse childhood experience groups). However, sensitivity (true-positive detection) and positive predictive values (presence of ill health among high-risk adverse childhood experience groups) were low, whereas positive likelihood ratios suggested only minimal-to-moderate increases in health risks among individuals reporting ≥4 adverse childhood experiences versus that among those reporting 0–3. // Conclusions: These findings suggest that screening based on the adverse childhood experience score does not accurately identify those individuals at high risk of health problems. This can lead to both allocation of unnecessary interventions and lack of provision of necessary support

When ignorance is bliss: weight perception, body mass index and quality of life in adolescents

Background/Objectives:Body weight is negatively associated with adolescent Health-Related Quality of Life (HRQoL). Despite this well-established relationship, some adolescents with obesity do not display the expected HRQoL decreases. This study hypothesised weight perception as a moderator of the association between weight status and adolescent HRQoL.Subjects/Methods:Subjects were secondary school students from an obesity prevention project in the Barwon South-West region of Victoria, Australia, entitled It’s Your Move (N=3040). Measures included standardised body mass index (BMI-z; World Health Organization growth standards), weight perception and HRQoL, measured by the Paediatric Quality of Life Inventory. Linear regression and average marginal effect analyses were conducted on cross-sectional baseline data to determine the significance of any interaction between weight perception and measured weight status in shaping adolescent HRQoL.Results:The BMI-z/perceived weight status interaction was significantly associated with adolescent HRQoL outcomes. Adolescents with BMI z-scores in the overweight/obesity range who perceived themselves as overweight had lower HRQoL than those who perceived themselves as ‘about right.’ Conversely, adolescents with BMI scores in the lower end of the normal range or in the thinness range who perceived themselves as underweight had lower HRQoL than those with ‘about right’ perceptions.Conclusions:This was the first study to report third-variable impacts of a body-perception variable on the relationship between adolescent weight status and HRQoL. Adolescents’ weight perceptions significantly moderated the relationship between overweight/obesity and reduced HRQoL. Adolescents who were outside the normal weight range and misperceived their objectively measured weight status enjoyed a higher HRQoL than adolescents whose weight perception was concordant with their actual weight status. These findings suggest that practitioners may need to exercise caution when educating adolescents about their weight status, as such ‘reality checks’ may negatively impact on adolescent HRQoL. It is suggested that more research be conducted to examine this potential effect

Discovery of heavy negative ions in Titan's ionosphere

Titan's ionosphere contains a rich positive ion population including organic molecules. Here, using CAPS electron spectrometer data from sixteen Titan encounters, we reveal the existence of negative ions. These ions, with densities up to similar to 100 cm similar to 3, are in mass groups of 10-30, 30-50, 50-80, 80-110, 110-200 and 200+ amu/charge. During one low encounter, negative ions with mass per charge as high as 10,000 amu/q are seen. Due to their unexpectedly high densities at similar to 950 km altitude, these negative ions must play a key role in the ion chemistry and they may be important in the formation of organic-rich aerosols (tholins) eventually falling to the surface

UC-318 Capstone Cybersecurity Website Hardening Group 2-01

The project we were given by Professor Privitera is to secure a web server that is a simulation of a genuine business with our case being a restaurant known as Akwaaba. The business website is hosted on Apache, MariaDB, Red Hat Linux, and PHP. We will first need to explore the network we were given to determine the system’s weaknesses to evaluate the risks and create a proper security policies plan with the help of the National Institute of Standards and Technology (NIST) standards. Following the security plan we created, our group will implement these changes into the network, hardening them to these standards. Finally, we will participate in a red/blue team cybersecurity ethical hacking procedure with our network and the two other teams. We will use white hat hacker skills to gain access to other groups’ networks while protecting our own network by patching up weaknesses if they have been breached

Neural and Aneural Regions Generated by the Use of Chemical Surface Coatings

The disordered environment found in conventional neural cultures impedes various applications where cell directionality is a key process for functionality. Neurons are highly specialized cells known to be greatly dependent on interactions with their surroundings. Therefore, when chemical cues are incorporated on the surface material, a precise control over neuronal behavior can be achieved. Here, the behavior of SH-SY5Y neurons on a variety of self-assembled monolayers (SAMs) and polymer brushes both in isolation and combination to promote cellular spatial control was determined. APTES and BIBB coatings promoted the highest cell viability, proliferation, metabolic activity, and neuronal maturation, while low cell survival was seen on PKSPMA and PMETAC surfaces. These cell-attractive and repulsive surfaces were combined to generate a binary BIBB-PKSPMA coating, whereby cellular growth was restricted to an exclusive neural region. The utility of these coatings when precisely combined could act as a bioactive/bioinert surface resulting in a biomimetic environment where control over neuronal growth and directionality can be achieved

Magnetic signatures of plasma-depleted flux tubes in the Saturnian inner magnetosphere

Initial Cassini observations have revealed evidence for interchanging magnetic flux tubes in the inner Saturnian magnetosphere. Some of the reported flux tubes differ remarkably by their magnetic signatures, having a depressed or enhanced magnetic pressure relative to their surroundings. The ones with stronger fields have been interpreted previously as either outward moving mass-loaded or inward moving plasma-depleted flux tubes based on magnetometer observations only. We use detailed multi-instrumental observations of small and large density depletions in the inner Saturnian magnetosphere from Cassini Rev. A orbit that enable us to discriminate amongst the two previous and opposite interpretations. Our analysis undoubtedly confirms the similar nature of both types of reported interchanging magnetic flux tubes, which are plasma-depleted, whatever their magnetic signatures are. Their different magnetic signature is clearly an effect associated with latitude. These Saturnian plasma-depleted flux tubes ultimately may play a similar role as the Jovian ones

Mechanical loading of tissue engineered skeletal muscle prevents dexamethasone induced myotube atrophy

Skeletal muscle atrophy as a consequence of acute and chronic illness, immobilisation, muscular dystrophies and aging, leads to severe muscle weakness, inactivity and increased mortality. Mechanical loading is thought to be the primary driver for skeletal muscle hypertrophy, however the extent to which mechanical loading can offset muscle catabolism has not been thoroughly explored. In vitro 3D-models of skeletal muscle provide a controllable, high throughput environment and mitigating many of the ethical and methodological constraints present during in vivo experimentation. This work aimed to determine if mechanical loading would offset dexamethasone (DEX) induced skeletal muscle atrophy, in muscle engineered using the C2C12 murine cell line. Mechanical loading successfully offset myotube atrophy and functional degeneration associated with DEX regardless of whether the loading occurred before or after 24 h of DEX treatment. Furthermore, mechanical load prevented increases in MuRF-1 and MAFbx mRNA expression, critical regulators of muscle atrophy. Overall, we demonstrate the application of tissue engineered muscle to study skeletal muscle health and disease, offering great potential for future use to better understand treatment modalities for skeletal muscle atrophy