Experiments in the Social Sciences: The relationship between External and Internal Validity

The article identifies a latent debate in the recent literature on the role and worth of experiments in economics and other social sciences concerning the relationship between the external and the internal validity of experimental designs. Our work identifies two incompatible views regarding the relationship between internal and external validity of experiments. While in the methodological literature references to the idea that there is a trade-off between the internal and external validity of experiments abound, this view coexists with the position stating that internal validity is rather a prerequisite of external validity. By identifying the contours of this implicit debate in the recent methodological literature around the use of experiments in the social sciences we call attention upon a series of insufficiently conceptualized issues regarding the central notions of internal and external validity and we question the standard view positing a trade-off between the two. This article stands against common associations of internal validity and external validity with the distinction between field and laboratory experiments and assesses critically the arguments that link the artificiality of experimental settings done in the laboratory with the purported trade-off between internal and external validity

Functional role of PGAM5 multimeric assemblies and their polymerization into filaments.

PGAM5 is a mitochondrial protein phosphatase whose genetic ablation in mice results in mitochondria-related disorders, including neurodegeneration. Functions of PGAM5 include regulation of mitophagy, cell death, metabolism and aging. However, mechanisms regulating PGAM5 activation and signaling are poorly understood. Using electron cryo-microscopy, we show that PGAM5 forms dodecamers in solution. We also present a crystal structure of PGAM5 that reveals the determinants of dodecamer formation. Furthermore, we observe PGAM5 dodecamer assembly into filaments both in vitro and in cells. We find that PGAM5 oligomerization into a dodecamer is not only essential for catalytic activation, but this form also plays a structural role on mitochondrial membranes, which is independent of phosphatase activity. Together, these findings suggest that modulation of the oligomerization of PGAM5 may be a regulatory switch of potential therapeutic interest

Progression and adherence to an individually prescribed and supervised resistance training intervention in older adults recovering in hospital from lower limb fragility fracture

This study evaluated adherence and progression with a 12-week resistance training program amongst a sample of older adults recovering in hospital from lower limb fragility fracture. Forty-nine participants (mean age 84 years) commenced the resistance training program seven days after the injury. The exercise prescription involved training of the hip and knee extensors, hip abductors, and ankle plantar- and dorsi flexors using resistive bands. Exercise sessions were completed tri-weekly for six weeks under supervision by a physiotherapist and tri-weekly for an additional six weeks independently. Adherence was assessed as the proportion of exercise sessions completed of those prescribed and any progression in resistance was documented. Level of adherence was not found to be influenced by age, gender, cognition or strength but was greater amongst those admitted from the community setting and for the first six weeks when supervision was present. Participants were able to obtain similar levels of resistance for the injured side compared to the noninjured side for all exercises excluding hip abduction and those admitted from the community setting achieved higher levels of resistance compared to those admitted from the residential care setting. These findings suggest that an early resistance training program is feasible and well tolerated amongst older adults recovering from lower limb fragility fracture. Further work is necessary to determine how this level of resistance training translates into functional improvements and how to improve adherence levels in clinical rehabilitation settings

Expanding Our Understanding of Adherence: The Role of Health Literacy and Cognitive Function in Adherence and Outcomes in Head and Neck Cancer

Background: Health literacy is the degree to which a person has the capacity to obtain, process, and understand basic information and services needed to make decisions about their health care. Poor health literacy has been associated with difficulties managing medications, assessing and evaluating health information, completing medical and financial forms, and comparing nutritional information of foods. As such, health literacy is closely related to adherence to medical treatment. Cognitive function contributes to one\u27s health literacy, though also independently contributes to adherence. Patients with head and neck cancers require complex, often multimodal care, and both health literacy and cognitive function have been found to be lower than the general population. However no study has examined the interaction between cognitive function and health literacy within treatment for head and neck cancer and outcomes. Objectives: To examine the role of cognitive function and health literacy in adherence to definitive and adjuvant radiotherapy and chemoradiotherapy and disease-free and overall survival in patients with head and neck cancer. Methods: 149 patients who received either definitive or adjuvant radiotherapy or chemoradiotherapy for squamous cell carcinoma of the head and neck and were assessed by psycho-oncology provider before initiating treatment were included. Patients between August 2017 through March 2020 were included. Patients were administered the Montreal Cognitive Assessment (MoCA) and the Rapid Estimate of Adult Literacy in Medicine (REALM-SF) by the psych-oncologist before starting treatment. Cancer and treatment related variables, including adherence, were obtained via chart review. Adherence was defined as having completed the treatment recommended by the Multi-disciplinary Tumor Board. Results: Patients were predominantly male (78%), white (73%), with an average age of 62 years (SD=9.1). The average years of education was 13.6 years (SD=2.6). The mean health literacy score was 6.3 out of 7 (SD=1.3, range 0-7), indicating reading at 7-8th grade level. The mean cognitive function score was 23.8 out of 30 (SD=3.6, range 10-30, scores less than 26 are indicative of cognitive impairment). Sixteen percent of patients were non-adherent to treatment recommendations and this was not associated with either health literacy or cognitive function (P=0.5 & 0.36, respectively). Lower health literacy was associated with later stage at presentation (P\u3c0.05). Health literacy was not associated with disease-free or overall survival (P=0.66 & 0.11, respectively). However, cognitive function was associated with overall survival (P\u3c0.0001) but not disease-free survival (P=0.22). Conclusions: Psychosocial variables such as health literacy and cognitive function are infrequently considered or studied in head and neck cancer. However, there exists significant evidence that patients with head and neck cancer tend to have higher rates of cognitive impairment and lower health literacy than the general population. Further, literacy and cognitive function are known to contribute to health outcomes in other populations. The current study found that cognitive impairment, but not health literacy, is associated with overall survival, while not being associated with treatment adherence. Further research is needed into the pathways that cognitive function interacts with cancer care and survival. This study highlights the need for assessment of cognitive function in patients with head and neck cancer, as identification and intervention with these patients can aid in survival outcomes and quality of life

Slowing resource loops in the clothing industry through circular business model experimentation

No description supplie

Predictions of microbial thermal inactivation in solid foods: isothermal and non-isothermal conditions

This work focuses on the use of the Gompertz-inspired model to predict the thermal inactivation behaviour of microorganisms obtained in solid food products, validated for isothermal and non-isothermal conditions. Experiments were carried out in parsley, artificially inoculated with Listeria innocua. For the isothermal conditions tested, the predictive ability of the model was confined. The higher the temperature, the higher deviations observed (i.e. the model underestimates the inactivation behaviour). However, for the non-isothermal condition tested, the model predicted the microbial response accurately

On the use of the gompertz model to predict microbial thermal inactivation under isothermal and non-isothermal conditions

Food processes should be designed to provide an adequate margin of safety against microbiological risk of food poisoning and food spoilage throughout shelf life. In this field, the use of mathematical models that describe the microorganisms’ kinetics in such conditions is an important tool for convenient design, control and optimization of efficient processes. If those models are accurate and precise, one can extract the best aiming at predictive purposes. The Gompertz equation is commonly applied to describe sigmoidal kinetics. Besides the proven adequacy of the model in those kinetics descriptions, most of the reported works do not use Gompertz equation in the most convenient form, and insightful information could be obtained with re-parameterized forms. This work aims at reviewing the use of the Gompertz model to describe inactivation, as well as re-parameterized forms that include parameters related to the survival curve features. Microbial survival often presents a shoulder prior to inactivation, followed by a linear phase (corresponding to a maximum inactivation rate) and a tail residual population. The versatility of the Gompertz model in describing kinetics with different shapes, varying from a log-linear tendency till a complete sigmoidal shape, makes it attractive for predictive purposes, both under static and dynamic temperature conditions. Drawbacks and critical features of the model, when it is applied to microbial responses, will be overview.info:eu-repo/semantics/acceptedVersio

Promoting tau secretion and propagation by hyperactive p300/CBP via autophagy-lysosomal pathway in tauopathy.

BackgroundThe trans-neuronal propagation of tau has been implicated in the progression of tau-mediated neurodegeneration. There is critical knowledge gap in understanding how tau is released and transmitted, and how that is dysregulated in diseases. Previously, we reported that lysine acetyltransferase p300/CBP acetylates tau and regulates its degradation and toxicity. However, whether p300/CBP is involved in regulation of tau secretion and propagation is unknown.MethodWe investigated the relationship between p300/CBP activity, the autophagy-lysosomal pathway (ALP) and tau secretion in mouse models of tauopathy and in cultured rodent and human neurons. Through a high-through-put compound screen, we identified a new p300 inhibitor that promotes autophagic flux and reduces tau secretion. Using fibril-induced tau spreading models in vitro and in vivo, we examined how p300/CBP regulates tau propagation.ResultsIncreased p300/CBP activity was associated with aberrant accumulation of ALP markers in a tau transgenic mouse model. p300/CBP hyperactivation blocked autophagic flux and increased tau secretion in neurons. Conversely, inhibiting p300/CBP promoted autophagic flux, reduced tau secretion, and reduced tau propagation in fibril-induced tau spreading models in vitro and in vivo.ConclusionsWe report that p300/CBP, a lysine acetyltransferase aberrantly activated in tauopathies, causes impairment in ALP, leading to excess tau secretion. This effect, together with increased intracellular tau accumulation, contributes to enhanced spreading of tau. Our findings suggest that inhibition of p300/CBP as a novel approach to correct ALP dysfunction and block disease progression in tauopathy