Reductions to main meal portion sizes reduce daily energy intake regardless of perceived normality of portion size: a 5 day cross-over laboratory experiment

Background Smaller portions may help to reduce energy intake. However, there may be a limit to the magnitude of the portion size reduction that can be made before consumers respond by increasing intake of other food immediately or at later meals. We tested the theoretical prediction that reductions to portion size would result in a significant reduction to daily energy intake when the resulting portion was visually perceived as ‘normal’ in size, but that a reduction resulting in a ‘smaller than normal’ portion size would cause immediate or later additional eating. Methods Over three 5-day periods, daily energy intake was measured in a controlled laboratory study using a randomized crossover design (N = 30). The served portion size of the main meal component of lunch and dinner was manipulated in three conditions: ‘large-normal’ (747 kcal), ‘small-normal’ (543 kcal), and ‘smaller than normal’ (339 kcal). Perceived ‘normality’ of portion sizes was determined by two pilot studies. Ad libitum daily energy intake from all meals and snacks was measured. Results Daily energy intake in the ‘large-normal’ condition was 2543 kcals. Daily energy intake was significantly lower in the ‘small-normal’ portion size condition (mean difference − 95 kcal/d, 95% CI [− 184, − 6], p = .04); and was also significantly lower in the ‘smaller than normal’ than the ‘small-normal’ condition (mean difference − 210 kcal/d, 95% CI [− 309, − 111], p < .001). Contrary to predictions, there was no evidence that the degree of additional food consumption observed was greater when portions were reduced past the point of appearing normal in size. Conclusions Reductions to the portion size of main-meal foods resulted in significant decreases in daily energy intake. Additional food consumption did not offset this effect, even when portions were reduced to the point that they were no longer perceived as being normal in size. Trial registration Prospectively registered protocol and analysis plan: https://osf.io/natws/; retrospectively registered: https://clinicaltrials.gov/ct2/show/NCT03811210

A Comprehensive Workflow for General-Purpose Neural Modeling with Highly Configurable Neuromorphic Hardware Systems

In this paper we present a methodological framework that meets novel requirements emerging from upcoming types of accelerated and highly configurable neuromorphic hardware systems. We describe in detail a device with 45 million programmable and dynamic synapses that is currently under development, and we sketch the conceptual challenges that arise from taking this platform into operation. More specifically, we aim at the establishment of this neuromorphic system as a flexible and neuroscientifically valuable modeling tool that can be used by non-hardware-experts. We consider various functional aspects to be crucial for this purpose, and we introduce a consistent workflow with detailed descriptions of all involved modules that implement the suggested steps: The integration of the hardware interface into the simulator-independent model description language PyNN; a fully automated translation between the PyNN domain and appropriate hardware configurations; an executable specification of the future neuromorphic system that can be seamlessly integrated into this biology-to-hardware mapping process as a test bench for all software layers and possible hardware design modifications; an evaluation scheme that deploys models from a dedicated benchmark library, compares the results generated by virtual or prototype hardware devices with reference software simulations and analyzes the differences. The integration of these components into one hardware-software workflow provides an ecosystem for ongoing preparative studies that support the hardware design process and represents the basis for the maturity of the model-to-hardware mapping software. The functionality and flexibility of the latter is proven with a variety of experimental results

Non-locality in quantum field theory due to general relativity

We show that general relativity coupled to a quantum field theory generically leads to non-local effects in the matter sector. These non-local effects can be described by non-local higher dimensional operators which remarkably have an approximate shift symmetry. When applied to inflationary models, our results imply that small non-Gaussianities are a generic feature of models based on general relativity coupled to matter fields. However, these effects are too small to be observable in the cosmic microwave background

Conformational fingerprinting with Raman spectroscopy reveals protein structure as a translational biomarker of muscle pathology

\ua9 2024 The Royal Society of Chemistry.Neuromuscular disorders are a group of conditions that can result in weakness of skeletal muscles. Examples include fatal diseases such as amyotrophic lateral sclerosis and conditions associated with high morbidity such as myopathies (muscle diseases). Many of these disorders are known to have abnormal protein folding and protein aggregates. Thus, easy to apply methods for the detection of such changes may prove useful diagnostic biomarkers. Raman spectroscopy has shown early promise in the detection of muscle pathology in neuromuscular disorders and is well suited to characterising the conformational profiles relating to protein secondary structure. In this work, we assess if Raman spectroscopy can detect differences in protein structure in muscle in the setting of neuromuscular disease. We utilise in vivo Raman spectroscopy measurements from preclinical models of amyotrophic lateral sclerosis and the myopathy Duchenne muscular dystrophy, together with ex vivo measurements of human muscle samples from individuals with and without myopathy. Using quantitative conformation profiling and matrix factorisation we demonstrate that quantitative ‘conformational fingerprinting’ can be used to identify changes in protein folding in muscle. Notably, myopathic conditions in both preclinical models and human samples manifested a significant reduction in α-helix structures, with concomitant increases in β-sheet and, to a lesser extent, nonregular configurations. Spectral patterns derived through non-negative matrix factorisation were able to identify myopathy with a high accuracy (79% in mouse, 78% in human tissue). This work demonstrates the potential of conformational fingerprinting as an interpretable biomarker for neuromuscular disorders

Wake up, wake up! It's me! It's my life! patient narratives on person-centeredness in the integrated care context: a qualitative study

Person-centered care emphasizes a holistic, humanistic approach that puts patients first, at the center of medical care. Person-centeredness is also considered a core element of integrated care. Yet typologies of integrated care mainly describe how patients fit within integrated services, rather than how services fit into the patient's world. Patient-centeredness has been commonly defined through physician's behaviors aimed at delivering patient-centered care. Yet, it is unclear how 'person-centeredness' is realized in integrated care through the patient voice. We aimed to explore patient narratives of person-centeredness in the integrated care context

Issues potentially affecting quality of life arising from long-term medicines use: a qualitative study

Background Polypharmacy is increasing and managing large number of medicines may create a burden for patients. Many patients have negative views of medicines and their use can adversely affect quality of life. No studies have specifically explored the impact of general long-term medicines use on quality of life. Objective To determine the issues which patients taking long-term medicines consider affect their day-to-day lives, including quality of life. Setting Four primary care general practices in North West England Methods Face-to-face interviews with adults living at home, prescribed four or more regular medicines for at least 1 year. Interviewees were identified from primary care medical records and purposively selected to ensure different types of medicines use. Interviews were recorded, transcribed and analysed thematically. Results Twenty-one interviews were conducted and analysed. Patients used an average of 7.8 medicines, 51 % were preventive, 40 % for symptom relief and 9 % treatment. Eight themes emerged: relationships with health professionals, practicalities, information, efficacy, side effects, attitudes, impact and control. Ability to discuss medicines with health professionals varied and many views were coloured by negative experiences, mainly with doctors. All interviewees had developed routines for using multiple medicines, some requiring considerable effort. Few felt able to exert control over medicines routines specified by health professionals. Over half sought additional information about medicines whereas others avoided this, trusting in doctors to guide their medicines use. Patients recognised their inability to assess efficacy for many medicines, notably those used for prophylaxis. All were concerned about possible side effects and some had poor experiences of discussing concerns with doctors. Medicines led to restrictions on social activities and personal life to the extent that, for some, life can revolve around medicines. Conclusion There is a multiplicity and complexity of issues surrounding medicines use, which impact on day-to-day lives for patients with long-term conditions. While most patients adapt to long-term medicines use, others did so at some cost to their quality of life

Treatment strategies and prognostic factors of patients with primary germ cell tumors in the mediastinum

Se presenta una paciente que fue intervenida quirúrgicamente por presentar una lesión tumoral a nivel del mediastino anterior, totalmente asintomática y descubierta, de forma incidental (incidentaloma), en el estudio preoperatorio por padecer litiasis vesicular. La tumoración resultó ser, histológicamente, un teratoma quístico maduro. La paciente evolucionó satisfactoriamente.It presents a patient who was surgery because of a tumor at the level of the anterior mediastinum, totally asymptomatic and uncovered, incidentally (incidentaloma), in the preoperative study due to vesicular lithiasis. The tumor turned out to be, histologically, a mature cystic teratoma. The patient evolved satisfactorily

A Critique and an Appraisal of VLSI Models of Computation

Coordinated Science Laboratory was formerly known as Control Systems LaboratoryJoint Services Electronics Program / N00014-79-C-0424National Science Foundation / MCS-81-0555

In-vitro screen of prion disease susceptibility genes using the scrapie cell assay.

Prion diseases (transmissible spongiform encephalopathies) are fatal neurodegenerative diseases including Creutzfeldt-Jakob disease (CJD) in humans, scrapie in sheep and bovine spongiform encephalopathy (BSE) in cattle. While genome-wide association studies in human and quantitative trait loci mapping in mice have provided evidence for multiple susceptibility genes, few of these have been confirmed functionally. Phenotyping mouse models is generally the method of choice. However, this is not a feasible option where many novel genes, without pre-existing models, would need to be tested. We have therefore developed and applied an in-vitro screen to triage and prioritise candidate modifier genes for more detailed future studies which is faster, far more cost effective and ethical relative to mouse bioassay models. An in vitro prion bioassay, the scrapie cell assay (SCA), uses a neuroblastoma derived cell line (PK1) that is susceptible to RML prions and able to propagate prions at high levels. In this study, we have generated stable gene silencing and/or overexpressing PK1-derived cell lines to test whether perturbation of 14 candidate genes affects prion susceptibility. While no consistent differences were determined for seven genes, highly significant changes were detected for Zbtb38, Sorcs1, Stmn2, Hspa13, Fkbp9, Actr10 and Plg, suggesting that they play key roles in the fundamental processes of prion propagation or clearance. Many neurodegenerative diseases involve the accumulation of misfolded protein aggregates and "prion-like" seeding and spread has been implicated in their pathogenesis. It is therefore expected that some of these prion-modifier genes may be of wider relevance in neurodegeneration