A key feature of macroautophagy/autophagy is the formation of a transient de novo compartment called the phagophore, which envelops cytoplasmic material, ultimately enclosing it within an autophagosome, allowing it to be targeted for degradation. Schütter et al describe a novel mechanism that spatiotemporally coordinates phospholipid synthesis to drive phagophore expansion and autophagosome formation. These authors show that during starvation, fatty acids (FAs) are channeled into phospholipid synthesis, and the newly synthesized lipids are directed toward autophagosome biogenesis.Abbreviations ACS acyl-CoA synthetase; ER endoplasmic reticulum; FA fatty acid; FAS fatty acid synthetase; MCS membrane contact sites; PAS phagophore assembly site.Purpose This study investigated whether perceptual ratings of speech parameters were predictive of transcription intelligibility in quiet and in noise for speakers with Parkinson's disease (PD). Method Ten speakers with PD and five healthy controls read 56 sentences. One group of 60 listeners orthographically transcribed the sentences in quiet, and another group of 60 listeners transcribed in noise. An additional 23 listeners judged a variety of speech parameters, including articulation, prosody, resonance, voice quality, and ease of understanding on a visual analog scale. Scores of the visual analog scale ratings were regressed against transcription intelligibility in quiet and in noise. Results Perceptual ratings of all the speech parameters were lower for speakers with PD. Global speech understanding, indexed by ease of understanding ratings, was associated with transcription intelligibility in quiet and in noise with a stronger effect in noise. Among the rated speech parameters, ease of understanding and voice quality ratings were significant predictors of speech intelligibility in noise. Conclusions Speech in individuals with PD was more difficult for listeners to understand and was characterized by deficits in articulation, prosody, resonance, and voice quality compared to normal speech produced by healthy older adults. Ease of understanding ratings, even when performed in quiet, predicted intelligibility in noise. Poor voice quality ratings in PD, a sign of phonatory deficit, had a negative impact on intelligibility in noise for speakers with PD.General Pairwise Comparison (GPC) statistics, such as the net benefit and the win ratio, have been applied in clinical trial data analysis and design. In the literature, inferential methods based on re-sampling, asymptotic or exact methods have been proposed for these GPC statistics, but they have not been compared to each other. In this paper, the small sample bias of the variance estimation, Type I error control and 95% confidence interval coverage of the GPC inferential methods are evaluated using simulations. The exact permutation and bootstrap tests perform best in all evaluated aspects for the net benefit, while the exact bootstrap test performs best for the win ratio.Advance care planning is an opportunity for patients to express their priorities for future care. NHS England has outlined a commitment to end-of-life care, advocating a shift towards more patient-centred care. The NHS is encouraging the workforce to engage patients in conversations about what is important to them, shifting the focus from 'what is wrong with you' to 'what matters to you'. Traditionally, this was seen as the doctor's role but this conversation can and should happen with the wider skilled medical workforce. The key to advance care planning is to have these conversations early on when patients have the capacity to discuss their preferences for care. Advance care planning can occur in any setting where the patient is comfortable to have the conversation, be that at home, in the GP surgery, in hospital or another setting. Patients with advance care plans are more likely to have their wishes respected, have fewer unwanted interventions, experience reduced transitions between care settings and are more likely to die in their preferred place of death. Healthcare professionals have a duty to offer advance care planning to patients nearing the last phase of life so that care can be delivered to honour individual needs at the end of life.As the population ages, there is a higher prevalence of both dementia and conditions that require major surgery. However, patients with dementia undergoing surgery have poorer outcomes than surgical patients without dementia. This article explores new guidance about delivering perioperative care for patients with dementia presenting for surgery. Management of patients with cognitive changes begins with developing an understanding of the classifications and pathophysiology of these disease processes, and addressing any modifiable risk factors for developing dementia, postoperative cognitive decline and postoperative delirium.  https://www.selleckchem.com/products/perhexiline-maleate.html  Thorough preoperative assessment provides the opportunity to identify patients with and at risk of these cognitive impairments and to involve the appropriate multidisciplinary team in care planning. Once patients are identified, an individualised perioperative management plan addressing any issues surrounding capacity and consent, conduct of anaesthesia, possible polypharmacy and potential drug interactions, and postoperative pain management can improve quality of care and outcomes for these patients.The world's population is ageing rapidly, with significant increases in the numbers of the oldest old. This places great pressure on societies to adapt to this changing demography. Pertinent issues include provision of education and resource for long-term conditions. The priorities older people hold need to be fully understood and their contributions to society, often diverse and far-reaching, recognised with sincerity. Currently, health systems for older people can often feel reactive, fragmented and disjointed. These systems can harbour inequity and ageism, and leave both patients and health-care providers dissatisfied. Regarding the global context, the most rapidly ageing populations are in low- and middle-income countries. This partly reflects huge successes in the treatment and control of communicable diseases but gives rise to the challenge of the 'double burden', managing both communicable and non-communicable diseases simultaneously. Moreover, multimorbidity (suffering two or more chronic conditions) is commonplace and presents further challenges with regards to providing coordinated care.