Iterative model building, structure refinement and density modification with the PHENIX AutoBuild wizard.

The PHENIX AutoBuild wizard is a highly automated tool for iterative model building, structure refinement and density modification using RESOLVE model building, RESOLVE statistical density modification and phenix.refine structure refinement. Recent advances in the AutoBuild wizard and phenix.refine include automated detection and application of NCS from models as they are built, extensive model-completion algorithms and automated solvent-molecule picking. Model-completion algorithms in the AutoBuild wizard include loop building, crossovers between chains in different models of a structure and side-chain optimization. The AutoBuild wizard has been applied to a set of 48 structures at resolutions ranging from 1.1 to 3.2 A, resulting in a mean R factor of 0.24 and a mean free R factor of 0.29. The R factor of the final model is dependent on the quality of the starting electron density and is relatively independent of resolution

Iterative build OMIT maps: Map improvement by iterative model-building and refinement without model bias

A procedure for carrying out iterative model-building, density modification and refinement is presented in which the density in an OMIT region is essentially unbiased by an atomic model. Density from a set of overlapping OMIT regions can be combined to create a composite 'Iterative-Build' OMIT map that is everywhere unbiased by an atomic model but also everywhere benefiting from the model-based information present elsewhere in the unit cell. The procedure may have applications in the validation of specific features in atomic models as well as in overall model validation. The procedure is demonstrated with a molecular replacement structure and with an experimentally-phased structure, and a variation on the method is demonstrated by removing model bias from a structure from the Protein Data Bank

Care and communication between health professionals and patients affected by severe or chronic illness in community care settings: a qualitative study of care at the end of life

Background: Advance care planning (ACP) enables patients to consider, discuss and, if they wish, document their wishes and preferences for future care, including decisions to refuse treatment, in the event that they lose capacity to make decisions for themselves. ACP is a key component of UK health policy to improve the experience of death and dying for patients and their families. There is limited evidence about how patients and health professionals understand ACP, or when and how this is initiated. It is evident that many people find discussion of and planning for end of life care difficult, and tend to avoid the topic. Aim: To investigate how patients, their relatives and health professionals initiate and experience discussion of ACP and the outcomes of advance discussions in shaping care at the end of life. Design and data collection: Qualitative study with two workstreams: (1) interviews with 37 health professionals (general practitioners, specialist nurses and community nurses) about their experiences of ACP; and (2) longitudinal case studies of 21 patients with 6-month follow-up. Cases included a patient and, where possible, a nominated key relative and/or health professional as well as a review of medical records. Complete case triads were obtained for 11 patients. Four cases comprised the patient alone, where respondents were unable or unwilling to nominate either a family member or a professional carer they wished to include in the study. Patients were identified as likely to be within the last 6 months of life. Ninety-seven interviews were completed in total. Setting: General practices and community care settings in the East Midlands of England. Findings: The study found ACP to be uncommon and focused primarily on specific documented tasks involving decisions about preferred place of death and cardiopulmonary resuscitation, supporting earlier research. There was no evidence of ACP in nearly half (9 of 21) of patient cases. Professionals reported ACP discussions to be challenging. It was difficult to recognise when patients had entered the last year of life, or to identify their readiness to consider future planning. Patients often did not wish to do so before they had become gravely ill. Consequently, ACP discussions tended to be reactive, rather than pre-emptive, occurring in response to critical events or evidence of marked deterioration. ACP discussions intersected two parallel strands of planning: professional organisation and co-ordination of care; and the practical and emotional preparatory work that patients and families undertook to prepare themselves for death. Reference to ACP as a means of guiding decisions for patients who had lost capacity was rare. Conclusions: Advance care planning remains uncommon, is often limited to documentation of a few key decisions, is reported to be challenging by many health professionals, is not welcomed by a substantial number of patients and tends to be postponed until death is clearly imminent. Current implementation largely ignores the purpose of ACP as a means of extending personal autonomy in the event of lost capacity. Future work: Attention should be paid to public attitudes to death and dying (including those of culturally diverse and ethnic minority groups), place of death, resuscitation and the value of anticipatory planning. In addition the experiences and needs of two under-researched groups should be explored: the frail elderly, including those who manage complex comorbid conditions, unrecognised as vulnerable cases; and those patients affected by stigmatised conditions, such as substance abuse or serious mental illness who fail to engage constructively with services and are not recognised as suitable referrals for palliative and end of life care. Funding: The National Institute for Health Research Health Services and Delivery Research programme

Perspective: Measuring Sweetness in Foods, Beverages, and Diets: Toward Understanding the Role of Sweetness in Health.

Various global public health agencies recommend minimizing exposure to sweet-tasting foods or beverages. The underlying rationale is that reducing exposure to the perception of sweet tastes, without regard to the source of sweetness, may reduce preferences for sweetness, added sugar intake, caloric intake, and body weight. However, the veracity of this sequence of outcomes has yet to be documented, as revealed by findings from recent systematic reviews on the topic. Efforts to examine and document the effects of sweetness exposure are needed to support evidence-based recommendations. They require a generally agreed-upon methodology for measuring sweetness in foods, beverages, and the overall diet. Although well-established sensory evaluation techniques exist for individual foods in laboratory settings, they are expensive and time-consuming, and agreement on the optimal approach for measuring the sweetness of the total diet is lacking. If such a measure could be developed, it would permit researchers to combine data from different studies and populations and facilitate the design and conduct of new studies to address unresolved research questions about dietary sweetness. This narrative review includes an overview of available sensory techniques, their strengths and limitations, recent efforts to measure the sweetness of foods and diets across countries and cultures, and a proposed future direction for improving methods for measuring sweetness toward developing the data required to support evidence-based recommendations around dietary sweetness

JITTER: SPECIFICATION AND ASSESSMENT IN DIGITAL AUDIO EQUIPMENT Julian Dunn*

Timing jitter in digital audio equipment can subtley degrade the audio quality or even cause data transmission failure. This paper examines the jitter performance requirements for digital audio equipment in the context of the audibility of sampling jitter modulation effects and the digital audio interface specification. It concludes by presenting techniques for the measurement of jitter performance. 1