Atmospheric waves and global seismoacoustic observations of the January 2022 Hunga eruption, Tonga.

The 15 January 2022 climactic eruption of Hunga volcano, Tonga, produced an explosion in the atmosphere of a size that has not been documented in the modern geophysical record. The event generated a broad range of atmospheric waves observed globally by various ground-based and spaceborne instrumentation networks. Most prominent was the surface-guided Lamb wave (≲0.

Copper-catalyzed dicarbonyl stress in NAFLD mice: protective effects of Oleuropein treatment on liver damage.

Background: Nonalcoholic fatty liver disease (NAFLD) or more appropriately, metabolic associated fatty liver disease (MAFLD), is the hepatic manifestation of metabolic syndrome. An imbalance of copper homeostasis has been described in the progression of NAFLD/MAFLD toward NASH/MASH. We were interested in understanding whether the chelating activity of Oleuropein (Ole) was able to improve the copper accumulation and the related pro-oxidant and glycative damage in the liver of mice fed HFD.

Transthyretin amyloid fibrils alter primary fibroblast structure, function, and inflammatory gene expression.

Age-related wild-type transthyretin amyloidosis (wtATTR) is characterized by systemic deposition of amyloidogenic fibrils of misfolded transthyretin (TTR) in the connective tissue of many organs. In the heart, this leads to cardiac dysfunction, which is a significant cause of age-related heart failure. The hypothesis tested is that TTR affects cardiac fibroblasts in ways that may contribute to fibrosis.

Molecular determinants of response to PI3K/akt/mTOR and KRAS pathways inhibitors in NSCLC cell lines.

Despite the impressive results obtained in the preclinical setting, all the inhibitors targeting two central cascades in cancer, the PI3K/akt/mTOR and the KRAS/MEK/ERK pathways, have shown, apart from very few exceptions, disappointing efficacy when translated to the clinic. One of the main reasons of their clinical failure seems to be the lack of a clear molecular determinant of response to these drugs. In this study, we tried to address this point by evaluating the cytotoxic activity of different inhibitors targeting the two pathways at different levels in a panel of ten NSCLC cell lines harboring alterations in PI3K, KRAS or both.

Co-creation of services to maintain independence and optimise well-being: Learnings from Australia's Older Women Living Alone (OWLA) project.

For many populations at risk of social isolation, including Older Women Living Alone (OWLA), existing services to maintain independence and optimise well-being are difficult to access, unsuitable or unavailable. Co-creation is a strategy to develop 'person-centred' services that meet the needs of individuals. We adapted an existing framework for co-creation and used participatory action research methods, supported by an evidence base comprising a systematic review, analysis of routinely collected data and interviews, to develop person-centred services for OWLA.

LKB1 Deficiency Renders NSCLC Cells Sensitive to ERK Inhibitors.

Introduction: Serine/threonine kinase 11 (LKB1/STK11) is one of the most mutated genes in NSCLC accounting for approximately one-third of cases and its activity is impaired in approximately half of KRAS-mutated NSCLC. At present, these patients cannot benefit from any specific therapy.

Methods: Through CRISPR/Cas9 technology, we systematically deleted LKB1 in both wild-type (WT) and KRAS-mutated human NSCLC cells.

Using co-creation and multi-criteria decision analysis to close service gaps for underserved populations.

Background: Navigating treatment pathways remains a challenge for populations with complex needs due to bottlenecks, service gaps and access barriers. The application of novel methods may be required to identify and remedy such problems.

Objective: To demonstrate a novel approach to identifying persistent service gaps, generating potential solutions and prioritizing action.

Correction to: Are Quality-Adjusted Life Years a Good Proxy Measure of Individual Capabilities?

Open Access This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0International License.

Economic evaluation of simulated and traditional clinical placements in occupational therapy education.

Introduction: This economic evaluation complements results of the randomised controlled trial that established non-inferiority of the learning outcomes of a one-week simulated clinical placement (SCP) in occupational therapy qualifying degrees in comparison to an equivalent traditional clinical placement (TCP). This companion study presents detailed cost analyses of two placement alternatives and a cost-benefit study to assess the value for money of SCP. An economic evaluation of simulated versus traditional placements has not previously been conducted in Australia.

Generation and characterization of MEK and ERK inhibitors- resistant non-small-cells-lung-cancer (NSCLC) cells.

Background: The RAS/RAF/MEK/ERK pathway is one of the most downregulated pathway in cancer. Inhibitors of RAF and MEK have established clinical use while ERK inhibitors recently faced the clinic. We aimed to generate resistant cell lines which could be helpful for defining new combinations able to overcome resistance.

Sharing and the Provision of "Cost-Ineffective" Life-Extending Services to Less Severely Ill Patients.

Background: Cost-utility analysis prioritizes services using cost, life-years, and the health state utility of the life-years. Nevertheless, a significant body of evidence suggests that the public would prefer more variables to be considered in decision making and at least some sharing of the budget with services for severe conditions that are not cost-effective because of their high cost.

Objectives: To examine whether this preference for sharing persists for less severe conditions when both cost effectiveness and illness severity would indicate that resources should be allocated to other services.

Uncertainty and the Undervaluation of Services for Severe Health States in Cost-Utility Analyses.

Objectives: To test the hypothesis that the "severity effect"-the preference for more than utility-maximizing expenditure on severe health states-may be the result of, or exacerbated by, the uncertainty associated with the chance of contracting the illness that causes the severe health state.

Methods: Survey respondents were asked to imagine that they will contract one of two illnesses and asked to allocate a budget between two insurance policies, each of which provides services for the treatment of one of the illnesses. A person's final health state varied with the amount of insurance purchased for the illness that occurred and therefore with the level of treatment.

Does a patient's health potential affect the social valuation of health services?

Background: Patients with a permanent impairment may be unable to reach full health. Consequently health services which cure illnesses which are unrelated to the impairment may increase health less than services for patients with no impairment. While it has been argued that this should not lead to discrimination against impaired patients there is little evidence to determine whether this equity-efficiency trade-off is consistent with social values.

Communal Sharing and the Provision of Low-Volume High-Cost Health Services: Results of a Survey.

Introduction: This paper suggests and tests a reason why the public might support the funding of services for rare diseases (SRDs) when the services are effective but not cost effective, i.e. when more health could be produced by allocating funds to other services.

Wee1 inhibitor MK1775 sensitizes KRAS mutated NSCLC cells to sorafenib.

Non-Small-Cell Lung Cancer (NSCLC) is a poorly chemosensitive tumor and targeted therapies are only used for about 15% of patients where a specific driving and druggable lesion is observed (EGFR, ALK, ROS). KRAS is one of the most frequently mutated genes in NSCLC and patients harboring these mutations do not benefit from specific treatments. Sorafenib, a multi-target tyrosine kinase inhibitor, was proposed as a potentially active drug in KRAS-mutated NSCLC patients, but clinical trials results were not conclusive.

Does the use of the proportional shortfall help align the prioritisation of health services with public preferences?

It has been proposed that equity may be included in the economic evaluation of health services using the 'proportional shortfall' (PS)-the proportion of a person's QALY expectation that they would lose because of an illness. The present paper reports the results of a population survey designed to test whether PS helped to explain people's preferences for health services and whether it did this better than the absolute shortfall or the equity related variables that PS seeks to replace. Survey respondents were asked to allocate 100 votes between 13 scenarios and a standard scenario.

"Fibromyalgia and quality of life: mapping the revised fibromyalgia impact questionnaire to the preference-based instruments".

Background: The revised version of the Fibromyalgia Impact Questionnaire (FIQR) is one of the most widely used specific questionnaires in FM studies. However, this questionnaire does not allow calculation of QALYs as it is not a preference-based measure. The aim of this study was to develop mapping algorithm which enable FIQR scores to be transformed into utility scores that can be used in the cost utility analyses.

Are Quality-Adjusted Life Years a Good Proxy Measure of Individual Capabilities?

Background: There is a debate in the health economics literature concerning the most appropriate way of applying Amartya Sen's capability approach in economic evaluation studies. Some suggest that quality-adjusted life years (QALYs) alone are adequate while others argue that this approach is too narrow and that direct measures of capability wellbeing provide a more extensive application of Sen's paradigm.

Objective: This paper empirically explores whether QALYs provide a good proxy for individual capabilities.

Assessing the validity of the ICECAP-A capability measure for adults with depression.

Background: Effectiveness and cost-effectiveness are increasingly important considerations in determining which mental health services are funded. Questions have been raised concerning the validity of generic health status instruments used in economic evaluation for assessing mental health problems such as depression; measuring capability wellbeing offers a possible alternative. The aim of this study is to assess the validity of the ICECAP-A capability instrument for individuals with depression.

Volcanic tremor and plume height hysteresis from Pavlof Volcano, Alaska.

The March 2016 eruption of Pavlof Volcano, Alaska, produced an ash plume that caused the cancellation of more than 100 flights in North America. The eruption generated strong tremor that was recorded by seismic and remote low-frequency acoustic (infrasound) stations, including the EarthScope Transportable Array. The relationship between the tremor amplitudes and plume height changes considerably between the waxing and waning portions of the eruption.

Activity of Pan-Class I Isoform PI3K/mTOR Inhibitor PF-05212384 in Combination with Crizotinib in Ovarian Cancer Xenografts and PDX.

The Phosphatidyl inositol-3 kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) and c-Met signaling pathways are often deregulated in cancer. The two pathways are interconnected and at least c-Met has been implicated in drug resistance. The aim of the study was to assess in ovarian cancer preclinical models, the efficacy and tolerability of a dual PI3K mTOR inhibitor (PF-05212384 or gedatolisib) and a c-Met inhibitor (crizotinib) either as single agents or in combination.

Estimating Utility Weights for the Vision Related Quality of Life Index.

Purpose: The VisQoL instrument was constructed as a vision-specific addition to the AQoL-6D multi-attribute utility instrument. The composite instrument, the AQoL-7D, was assigned utility scores that are the basis for now estimating VisQoL utilities when it is used as a stand-alone instrument. This study aimed to construct mapping functions that allow utility scores to be assigned to the Vision Related Quality of Life (VisQoL) instrument, a stand-alone vision-specific quality-of-life measure.

Mapping Between the Sydney Asthma Quality of Life Questionnaire (AQLQ-S) and Five Multi-Attribute Utility Instruments (MAUIs).

Purpose: Economic evaluation of health services commonly requires information regarding health-state utilities. Sometimes this information is not available but non-utility measures of quality of life may have been collected from which the required utilities can be estimated. This paper examines the possibility of mapping a non-utility-based outcome, the Sydney Asthma Quality of Life Questionnaire (AQLQ-S), onto five multi-attribute utility instruments: Assessment of Quality of Life 8 Dimensions (AQoL-8D), EuroQoL 5 Dimensions 5-Level (EQ-5D-5L), Health Utilities Index Mark 3 (HUI3), 15 Dimensions (15D), and the Short-Form 6 Dimensions (SF-6D).