Thriving in the wake of a storm: A systematic qualitative review & meta-synthesis on facilitating post-traumatic growth in patients living with Acquired Brain Injury.

Acquired Brain Injury (ABI) often results in significant challenges, yet it may also facilitate Post-Traumatic Growth (PTG). This review explores a critical question: "What are the main factors contributing to PTG following ABI, and what potential barriers to its development are perceived by ABI survivors?" Here we aim to systematically uncover these contributors and barriers to PTG through a meta-synthesis, involving a comprehensive review of previously published qualitative research on this topic. A literature search was conducted across PsycINFO, CINAHL, and MEDLINE up to December 2022 to identify studies for inclusion. From an initial pool of 1,946 records, eleven articles were selected for inclusion. Reflexive thematic analysis yielded three analytical themes including "Journey to Self-Rediscovery", "Strength in Connection" and "Overcoming Obstacles". Our findings also revealed facilitators and barriers across multiple levels of scale including personal (e.g., acceptance versus resignation), interpersonal (e.g., positive social ties versus difficulties making social connections), and systemic (e.g., new meaning and purpose versus financial constraints) scales. Our research extends existing knowledge in ABI rehabilitation, providing a more nuanced understanding of the dynamics influencing PTG with implications for clinicians seeking to promote wellbeing following brain injury.

Crystal Structure of Non-Structural Protein 10 from Severe Acute Respiratory Syndrome Coronavirus-2.

Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), causing Coronavirus Disease 19 (COVID-19), emerged at the end of 2019 and quickly spread to cause a global pandemic with severe socio-economic consequences. The early sequencing of its RNA genome revealed its high similarity to SARS, likely to have originated from bats. The SARS-CoV-2 non-structural protein 10 (nsp10) displays high sequence similarity with its SARS homologue, which binds to and stimulates the 3'-to-5' exoribonuclease and the 2'-O-methlytransferase activities of nsps 14 and 16, respectively. Here, we report the biophysical characterization and 1.6 Å resolution structure of the unbound form of nsp10 from SARS-CoV-2 and compare it to the structures of its SARS homologue and the complex-bound form with nsp16 from SARS-CoV-2. The crystal structure and solution behaviour of nsp10 will not only form the basis for understanding the role of SARS-CoV-2 nsp10 as a central player of the viral RNA capping apparatus, but will also serve as a basis for the development of inhibitors of nsp10, interfering with crucial functions of the replication-transcription complex and virus replication.

Improved molecular recognition of Carbonic Anhydrase IX by polypeptide conjugation to acetazolamide.

The small molecule inhibitor acetazolamide (AZM) was conjugated to a set of designed polypeptides and the resulting conjugates were evaluated for their affinity to Human Carbonic Anhydrase II (HCA II) using surface plasmon resonance. The dissociation constant of the AZM-HCA II complex was 38nM and that of the AZM conjugated polypeptide (4-C10L17-AZM) to HCA II was found to be 4nM, an affinity enhancement of a factor of 10 due to polypeptide conjugation. For Human Carbonic Anhydrase IX (HCA IX) the dissociation constant of AZM was 3nM, whereas that of the 4-C10L17-AZM conjugate was 90pM, a 33-fold affinity enhancement. This dramatic affinity increase due to polypeptide conjugation was achieved for a small molecule ligand with an already high affinity to the target protein. This supports the concept that enhancements due to polypeptide conjugation are not limited to small molecule ligands that bind proteins in the mM to µM range but may be used also for nM ligands to provide recognition elements with dissociation constants in the pM range. Evaluations of two HCA IX constructs that do not carry the proteoglycan (PG) domain did not show significant affinity differences between AZM and the polypeptide conjugate, providing evidence that the improved binding of 4-C10L17-AZM to HCA IX emanated from interactions between the polypeptide segment and the PG domain found only in one carbonic anhydrase, HCA IX.

The extended impact of co-designed personalised aids for people living with chronic conditions: an exploratory study in a healthcare setting.

Assistive technology has great potential to help individuals living with chronic health conditions, however devices often fail to align with the unique requirements of users. These results in device abandonment and missed opportunities to benefit people. This exploratory study aims to evaluate the short and longer-term satisfaction, psychological benefit, use and resources involved in co-designed customised assistive devices within a current healthcare service. Individuals with chronic health conditions identified daily living challenges. Eleven individuals completed the trial and were involved throughout the design process. Outcome measures evaluated the impact of the devices provided, healthcare utilisation, help required, and resources used. Nineteen custom assistive devices were produced for twenty-four challenges in daily living identified. At 3-months, eighteen devices were still being used. Daily challenges had become easier for individuals to complete and required less help from informal carers. Individuals were satisfied with the devices and service provided. Improvements in competence, adaptability and self-esteem were sustained long-term. The average clinician's time required to produce a device was 5 h 55 min, with an average cost of £203.79. People with chronic conditions were able to benefit from the co-design process resulting in satisfaction and long-term utilisation of the device, and positive psycho-social benefits. The costs associated with embedding this approach in a healthcare service were calculated. Scaling up the co-design process reduced the associated costs per device compared to previous work. Further work is required to evaluate co-designing across larger samples and explore opportunities to further improve the cost-efficiency.

By involving users in the design process, healthcare professionals can create devices that better meet users' expectations, preferences and functional needs, thereby increasing overall usability, satisfaction and utilisation long-term of the devices.Incorporating the individual's perspective and needs into the design process enabled users to better understand the solutions that could be produced and thus encouraged users to identify other challenges in daily living they faced where an assistive device could assist them.Through being provided with devices to support them with specific challenges they faced, individuals were able to perform more tasks independently, reducing the need for help from family members and informal carers for the associated tasks.Re-evaluating the solutions generated with other previous research may help identify common design solutions and features to enable further scaling-up of this co-design approach.

Group-based positive psychotherapy for people living with acquired brain injury: a protocol for a feasibility study.

BACKGROUND: Acquired brain injury (ABI) and other chronic conditions are placing unprecedented pressure on healthcare systems. In the UK, 1.3 million people live with the effects of brain injury, costing the UK economy approximately £15 billion per year. As a result, there is an urgent need to adapt existing healthcare delivery to meet increasing current and future demands. A focus on wellbeing may provide an innovative opportunity to reduce the pressure on healthcare services while also supporting patients to live more meaningful lives. The overarching aims of the study are as follows: (1) evaluate the feasibility of conducting a positive psychotherapy intervention for individuals with ABI and (2) ascertain under what conditions such an intervention would merit a fully powered randomised controlled trial (RCT) compared to a standard control group (TAU). METHODS AND ANALYSIS: A randomised, two-arm feasibility trial involving allocation of patients to either a treatment group (positive psychotherapy) or control group (treatment as usual) group, according to a 1:1 ratio. A total of 60 participants at three sites will be recruited including 20 participants at each site. Assessments will be conducted at baseline, on completion of the 8-week intervention and 3 months following completion. These will include a range of questionnaire-based measures, psychophysiology and qualitative outcomes focusing on feasibility outcomes and participant experience. This study has been approved by the Wales Research Ethics Committee (IRAS project ID: 271,251, REC reference: 19/WA/0336). DISCUSSION: This study will be the first to examine the feasibility of an innovative, holistic positive psychotherapy intervention for people living with ABI, focused on individual, collective and planetary wellbeing, and will enable us to determine whether to proceed to a full randomised controlled trial. TRIAL REGISTRATION: ISRCTN12690685 , registered 11th November 2020.

Can a previously co-designed device be used by others? A service evaluation of the use of the Sativex spray holder for individuals with multiple sclerosis.

PURPOSE: Co-design has previously been used to design custom assistive devices, involving the end user in the process to ensure the device meets their needs. From devices previously created, designs could be re-used and modified to meet variations in the needs of other individuals with similar clinical needs. This service evaluation explored the re-usability of a holder for helping administer the spray medication Sativex, for individuals with multiple sclerosis. METHODS: This evaluation was conducted in a UK based Rehabilitation Engineering NHS department. Five individuals who were currently prescribed Sativex trialled the device and provided feedback to further customise the device. Questionnaires evaluated the satisfaction and impact of the devices provided. The resources to provide the devices were calculated. RESULTS: Three of the five individuals who trialled the Sativex spray holder were using long term. Modifications to the shape of the holder were made due to differences in hand strength and dexterity from the initial user. Results indicated high satisfaction with the device and service provided, with improvements in the individuals' competence, adaptability and self-esteem. The mean cost of providing and modifying the device was £78.62. CONCLUSIONS: The previously co-designed Sativex spray holder was used by other individuals, demonstrating how a co-design framework can be used to identify user needs and modifications to previous designs and then implement design changes. The wider use of the device helped off-set the initial costs associated with co-designing devices. Further work is required to explore how other devices could be modified to meet individual needs.IMPLICATIONS FOR REHABILITATIONA previously co-designed assistive device was re-used and modified to accommodate for variation's in the different needs of individual users, for example due to differences in hand strength and dexterity.Through utilising a robust framework to identify user needs, deviations from the original design were identified and implemented. This improved the cost-effectiveness associated with co-designing custom assistive devices, off-setting the initial high cost associated with producing a custom device.There are secondary benefits to initially co-designing devices within healthcare settings beyond the initial user through re-using and modifying devices.

Inhibition of D-xylose isomerase by polyols: atomic details by joint X-ray/neutron crystallography.

D-Xylose isomerase (XI) converts the aldo-sugars xylose and glucose to their keto analogs xylulose and fructose, but is strongly inhibited by the polyols xylitol and sorbitol, especially at acidic pH. In order to understand the atomic details of polyol binding to the XI active site, a 2.0 Å resolution room-temperature joint X-ray/neutron structure of XI in complex with Ni(2+) cofactors and sorbitol inhibitor at pH 5.9 and a room-temperature X-ray structure of XI containing Mg(2+) ions and xylitol at the physiological pH of 7.7 were obtained. The protonation of oxygen O5 of the inhibitor, which was found to be deprotonated and negatively charged in previous structures of XI complexed with linear glucose and xylulose, was directly observed. The Ni(2+) ions occupying the catalytic metal site (M2) were found at two locations, while Mg(2+) in M2 is very mobile and has a high B factor. Under acidic conditions sorbitol gains a water-mediated interaction that connects its O1 hydroxyl to Asp257. This contact is not found in structures at basic pH. The new interaction that is formed may improve the binding of the inhibitor, providing an explanation for the increased affinity of the polyols for XI at low pH.

Room-temperature ultrahigh-resolution time-of-flight neutron and X-ray diffraction studies of H/D-exchanged crambin.

The room-temperature (RT) X-ray structure of H/D-exchanged crambin is reported at 0.85 Å resolution. As one of the very few proteins refined with anisotropic atomic displacement parameters at two temperatures, the dynamics of atoms in the RT and 100 K structures are compared. Neutron diffraction data from an H/D-exchanged crambin crystal collected at the Protein Crystallography Station (PCS) showed diffraction beyond 1.1 Å resolution. This is the highest resolution neutron diffraction reported to date for a protein crystal and will reveal important details of the anisotropic motions of H and D atoms in protein structures.

Wellbeing, Whole Health and Societal Transformation: Theoretical Insights and Practical Applications.

Society faces several major interrelated challenges which have an increasingly profound impact on global health including inequalities, inequities, chronic disease and the climate catastrophe. We argue here that a focus on the determinants of wellbeing across multiple domains offers under-realised potential for promoting the 'whole health' of individuals, communities and nature. Here, we review recent theoretical innovations that have laid the foundations for our own theoretical model of wellbeing - the GENIAL framework - which explicitly links health to wellbeing, broadly defined. We emphasise key determinants across multiple levels of scale spanning the individual, community and environmental levels, providing opportunities for positive change that is either constrained or facilitated by a host of sociostructural factors lying beyond the immediate control of the individual (e.g. social cohesion and health-related inequities can either promote or adversely impact on wellbeing, respectively). Following this, we show how the GENIAL theoretical framework has been applied to various populations including university students and people living with neurological disorders, with a focus on acquired brain injury. The wider implication of our work is discussed in terms of its contribution to the understanding of 'whole health' as well as laying the foundations for a 'whole systems' approach to improving health and wellbeing in a just and sustainable way.

Assessing the use of co-design to produce bespoke assistive technology solutions within a current healthcare service: a service evaluation.

PURPOSE: Co-design involves engaging with the end-user in the design process and may help reduce the barriers to assistive technology use. Previous research has used co-design in the provision of assistive technology, but no research has looked at applying it within a healthcare setting. This service evaluation examines the use of co-design in providing customized assistive devices within a current UK healthcare based Rehabilitation Engineering department. METHODS: This evaluation reports on three case studies. Individuals identified a range of challenges in daily living. The participants worked with the clinician in trialling prototypes and providing feedback to develop custom devices. A mixed-method approach of questionnaires and semi-structured interviews were used to evaluate the devices provided and the co-design approach. The resources required to provide the device were also calculated. RESULTS: Five different devices were developed, which were able to overcome the challenges identified. Results indicated participants were satisfied with both the devices and service provided. Participants expressed other benefits including increased independence, increased positive emotions and reduced mental load. Participants indicated they liked being involved in the design process and their feedback helped ensure the devices were customized to their needs. CONCLUSIONS: The use of co-design was able to produce customized assistive device that met the needs of the individuals within a current healthcare service. Further work is required to assess the feasibility of utilising a co-design approach for the provision of other custom assistive technology in the future and explore if this can overcome the barriers to assistive technology use.Implications for rehabilitationEnd-user involvement, the design process can help enable customized assistive devices to be provided that better meet the user's needs.The custom assistive devices provided not only helped the individuals overcome the challenges identified but had wider reaching benefits for the individuals physical and mental health and wellbeing.End-users valued being able to input into the co-design process and working closely with the clinician in developing the device.

Riding the wave into wellbeing: A qualitative evaluation of surf therapy for individuals living with acquired brain injury.

Nature has long demonstrated the capacity to facilitate wellbeing. Interventions involving the natural environment such as surf therapy, are increasingly being used to facilitate aspects of wellbeing in clinical populations. However, explorations of how nature-based interventions such as surf therapy may be used to promote wellbeing in the context of neurorehabilitation are missing from the peer-reviewed literature. Here we characterize the experience of a five-week surfing intervention involving fifteen adults living with the psycho-social and cognitive sequelae of acquired brain injury. Insights were analysed using reflexive thematic analysis, which highlighted the importance of seven overarching themes, including: 1) Connection to Nature, 2) Facilitating Trust and Safety, 3) Managing and Accepting Difficult Emotions, 4) Facilitating Positive Emotion, Meaning and Purpose, 5) Building Community through Social Connection, and 6) Positive Change. Barriers and opportunities (theme 7) were also identified as components on which clinical services may be improved. We present a theoretical model for the benefits of surf therapy in people living with acquired brain injury (ABI) based on these themes and reflections on findings from the wider literature. Findings emphasise the importance of leveraging community partnerships to augment the holistic model of neurorehabilitation and potential implications for service redesign are discussed, focusing on recent developments in wellbeing science.

Exploring the barriers to using assistive technology for individuals with chronic conditions: a meta-synthesis review.

PURPOSE: Assistive technology can provide a key tool to enabling independence, greater inclusion and participation in society for individuals with chronic conditions. This potential is currently not always realized due to barriers to accessing and using assistive technology. This review aims to identify the common barriers to acquiring and using assistive technology for users with chronic conditions through a systematic meta-synthesis. This differs from other systematic reviews by applying a transdiagnostic approach to identify if barriers are common across chronic conditions. MATERIALS AND METHODS: A systematic literature search of five scientific databases (PubMed, SCOPUS, PsycINFO, CINAHL and Medline) was conducted to identify relevant qualitative studies. The search was conducted in November 2019. For the identified articles, thematic content analysis was conducted and the methodological quality was evaluated using the Critical Appraisal Skills Programme (CASP) checklist for qualitative research. RESULTS: Forty papers met the inclusion criteria and were included in the analysis. Fifty-one descriptive themes grouped into six overarching analytical themes were identified from the studies. The analytical themes identified were: the design and function of the assistive technology, service provision, information and awareness, psychological barriers, support network and societal barriers. CONCLUSIONS: The barriers are interconnected and common across different health conditions. More involvement in personalized care for developing strategies, adaptation of home technologies and provision of assistive technology could overcome the service provision and design barriers to assistive technology. Accessible information and providing greater awareness will be important to overcoming information, psychological and societal barriers to assistive technology.Implications for rehabilitationIndividuals with chronic conditions face complex barriers to acquiring and using assistive technology as a result of the devices themselves, their individual context, the healthcare context where assistive technology is provided and wider societal barriers.The provision of assistive technology needs to change away from the traditional medical model of the "expert" clinician and instead focus on more user involvement to deliver personalised care that utilises the users lived knowledge and experiences.Assistive technology provision should be considered alongside how to adapt everyday mainstream technology to meet user needs; the provision of devices should encourage creative problem solving rather then relying on pre-defined prescription lists of assistive technology.

Identifying Suitable Cognitive Assessments for Children and Adolescents with Acquired Brain Injury for use by Occupational Therapists in Acute and Subacute Hospital Contexts: A Scoping Review.

AIM: To appraise the literature evaluating psychometric properties and clinical utility of cognitive assessments available for use by occupational therapists in acute and subacute hospital contexts with children aged 4-18 years diagnosed with an acquired brain injury. METHODS: Scoping review. Assessments and associated studies were evaluated for their methodologic quality using the COnsensus-based standard for the Selection of health Measurement INstruments (COSMIN) strategy. RESULTS: Forty-one studies evaluated 49 different assessments and reported on assessment psychometrics (n = 40), clinical utility (n = 1) and five reported on both. Fourteen assessments with the strongest psychometric properties and clinical utility were shortlisted. CONCLUSION: A gold standard assessment was not identified. Instead, a shortlist of functional, performance-based, technology-based, and self-report assessments were identified as relevant for the setting and population, but requiring further investigation. Future development of a cognitive assessment in partnership with therapists working in tertiary pediatric settings will ensure optimal clinical utility and validity.

Identification of fragments binding to SARS-CoV-2 nsp10 reveals ligand-binding sites in conserved interfaces between nsp10 and nsp14/nsp16.

Since the emergence of SARS-CoV-2 in 2019, Covid-19 has developed into a serious threat to our health, social and economic systems. Although vaccines have been developed in a tour-de-force and are now increasingly available, repurposing of existing drugs has been less successful. There is a clear need to develop new drugs against SARS-CoV-2 that can also be used against future coronavirus infections. Non-structural protein 10 (nsp10) is a conserved stimulator of two enzymes crucial for viral replication, nsp14 and nsp16, exhibiting exoribonuclease and methyltransferase activities. Interfering with RNA proofreading or RNA cap formation represents intervention strategies to inhibit replication. We applied fragment-based screening using nano differential scanning fluorometry and X-ray crystallography to identify ligands targeting SARS-CoV-2 nsp10. We identified four fragments located in two distinct sites: one can be modelled to where it would be located in the nsp14-nsp10 complex interface and the other in the nsp16-nsp10 complex interface. Microscale thermophoresis (MST) experiments were used to quantify fragment affinities for nsp10. Additionally, we showed by MST that the interaction by nsp14 and 10 is weak and thereby that complex formation could be disrupted by small molecules. The fragments will serve as starting points for the development of more potent analogues using fragment growing techniques and structure-based drug design.

Neutron structure of human carbonic anhydrase II: a hydrogen-bonded water network "switch" is observed between pH 7.8 and 10.0.

The neutron structure of wild-type human carbonic anhydrase II at pH 7.8 has been determined to 2.0 Å resolution. Detailed analysis and comparison to the previously determined structure at pH 10.0 show important differences in the protonation of key catalytic residues in the active site as well as a rearrangement of the H-bonded water network. For the first time, a completed H-bonded network stretching from the Zn-bound solvent to the proton shuttling residue, His64, has been directly observed.

High-resolution neutron crystallographic studies of the hydration of the coenzyme cob(II)alamin.

The hydration of the coenzyme cob(II)alamin has been studied using high-resolution monochromatic neutron crystallographic data collected at room temperature to a resolution of 0.92 Å on the original D19 diffractometer with a prototype 4° × 64° detector at the high-flux reactor neutron source run by the Institute Laue-Langevin. The resulting structure provides hydrogen-bonding parameters for the hydration of biomacromolecules to unprecedented accuracy. These experimental parameters will be used to define more accurate force fields for biomacromolecular structure refinement. The presence of a hydrophobic bowl motif surrounded by flexible side chains with terminal functional groups may be significant for the efficient scavenging of ligands. The feasibility of extending the resolution of this structure to ultrahigh resolution was investigated by collecting time-of-flight neutron crystallographic data during commissioning of the TOPAZ diffractometer with a prototype array of 14 modular 2° × 21° detectors at the Spallation Neutron Source run by Oak Ridge National Laboratory.

Moving Beyond Disciplinary Silos Towards a Transdisciplinary Model of Wellbeing: An Invited Review.

The construct of wellbeing has been criticised as a neoliberal construction of western individualism that ignores wider systemic issues such as inequality and anthropogenic climate change. Accordingly, there have been increasing calls for a broader conceptualisation of wellbeing. Here we impose an interpretative framework on previously published literature and theory, and present a theoretical framework that brings into focus the multifaceted determinants of wellbeing and their interactions across multiple domains and levels of scale. We define wellbeing as positive psychological experience, promoted by connections to self, community and environment, supported by healthy vagal function, all of which are impacted by socio-contextual factors that lie beyond the control of the individual. By emphasising the factors within and beyond the control of the individual and highlighting how vagal function both affects and are impacted by key domains, the biopsychosocial underpinnings of wellbeing are explicitly linked to a broader context that is consistent with, yet complementary to, multi-levelled ecological systems theory. Reflecting on the reciprocal relationships between multiple domains, levels of scale and related social contextual factors known to impact on wellbeing, our GENIAL framework may provide a foundation for a transdisciplinary science of wellbeing that has the potential to promote the wellbeing of individuals while also playing a key role in tackling major societal challenges.

The Impact of Psycho-Social Interventions on the Wellbeing of Individuals With Acquired Brain Injury During the COVID-19 Pandemic.

Individuals with Acquired Brain Injury (ABI) suffer chronic impairment across cognitive, physical and psycho-social domains, and the experience of anxiety, isolation and apathy has been amplified by the COVID-19 pandemic. A qualitative evaluation was conducted of 14 individuals with ABI who had participated in series of COVID adapted group-based intervention(s) that had been designed to improve wellbeing. Eight themes were identified: Facilitating Safety, Fostering Positive Emotion, Managing and Accepting Difficult Emotions, Promoting Meaning, Finding Purpose and Accomplishment, Facilitating Social Ties, (Re)Connecting to Nature, and Barriers to Efficacy. Findings are discussed with respects to recent theoretical developments in positive psychology and wellbeing science and support the use of online and outdoor interventions to enhance wellbeing in individuals living with ABI during the COVID-19 pandemic. This paper makes a unique contribution to second wave positive psychology (PP2.0) through the application of recent advances in wellbeing science to an ABI population during the COVID-19 pandemic. In doing so, this paper lays the foundation for new interventions that not only reduce impairment and distress, but also create opportunities for meaning and enhanced wellbeing in people living with chronic conditions and those individuals living with ABI in particular.

Protectors of Wellbeing During the COVID-19 Pandemic: Key Roles for Gratitude and Tragic Optimism in a UK-Based Cohort.

The COVID-19 pandemic has presented a global threat to physical and mental health worldwide. Research has highlighted adverse impacts of COVID-19 on wellbeing but has yet to offer insights as to how wellbeing may be protected. Inspired by developments in wellbeing science and guided by our own theoretical framework (the GENIAL model), we examined the role of various potentially protective factors in a sample of 138 participants from the United Kingdom. Protective factors included physical activity (i.e., a health behaviour that helps to build psychological wellbeing), tragic optimism (optimism in the face of tragedy), gratitude (a prosocial emotion), social support (the perception or experience of being loved, cared for, and valued by others), and nature connectedness (physical and psychological connection to nature). Initial analysis involved the application of one-sample t-tests, which confirmed that wellbeing (measured by the Warwick-Edinburgh Mental Well-being scale) in the current sample (N = 138; M = 46.08, SD = 9.22) was significantly lower compared to previous samples (d = -0.36 and d = -0.41). Protective factors were observed to account for up to 50% of variance in wellbeing in a hierarchical linear regression that controlled for a range of sociostructural factors including age, gender, and subjective social status, which impact on wellbeing but lie beyond individual control. Gratitude and tragic optimism emerged as significant contributors to the model. Our results identify key psychological attributes that may be harnessed through various positive psychology strategies to mitigate the adverse impacts of hardship and suffering, consistent with an existential positive psychology of suffering.

Macromolecular neutron crystallography at the Protein Crystallography Station (PCS).

The Protein Crystallography Station (PCS) at Los Alamos Neutron Science Center is a high-performance beamline that forms the core of a capability for neutron macromolecular structure and function determination. Neutron diffraction is a powerful technique for locating H atoms and can therefore provide unique information about how biological macromolecules function and interact with each other and smaller molecules. Users of the PCS have access to neutron beam time, deuteration facilities, the expression of proteins and the synthesis of substrates with stable isotopes and also support for data reduction and structure analysis. The beamline exploits the pulsed nature of spallation neutrons and a large electronic detector in order to collect wavelength-resolved Laue patterns using all available neutrons in the white beam. The PCS user facility is described and highlights from the user program are presented.