Supported Privacy: An Essential Principle for End-of-Life Care for Children and Families in the PICU.

Caring for children and their families at the end-of-life is an essential but challenging aspect of care in the PICU. During and following a child's death, families often report a simultaneous need for protected privacy and ongoing supportive presence from staff. Balancing these seemingly paradoxical needs can be difficult for PICU staff and can often lead to the family feeling intruded upon or abandoned during their end-of-life experience. In this "Pediatric Critical Care Medicine Perspectives" piece, we reframe provision of privacy at the end-of-life in the PICU and describe an essential principle that aims to help the interprofessional PICU team simultaneously meet these two opposing family needs: "Supported Privacy." In addition, we offer concrete recommendations to actualize "Supported Privacy" in the PICU, focusing on environmental considerations, practical needs, and emotional responses. By incorporating the principles of "Supported Privacy" into end-of-life care practices, clinicians can support the delivery of high-quality care that meets the needs of children and families navigating the challenges and supports of end-of-life in the PICU.

"We want to include him in that journey": A qualitative descriptive study of parental experiences and considerations for sibling inclusion in the paediatric ICU.

OBJECTIVES: Siblings are an important yet often forgotten part of the paediatric intensive care unit (PICU) family experience. Commonly, siblings are supported through the experience by their parents; however, very little is known about parental experiences of providing this support. This study aims to explore parental experiences of supporting sibling inclusion in PICU. RESEARCH METHODOLOGY/DESIGN: This study utilised a qualitative descriptive approach to conduct semi-structured interviews with 6 parents of 5 children with congenital heart disease who had spent time in PICU. Data were analysed using reflexive thematic analysis. SETTING: Australian PICUs. FINDINGS: Parental considerations and experiences for sibling inclusion were identified across three key phases: Pre-inclusion, The PICU visit, and Post-inclusion. Prior to including siblings in PICU, parents considered various ways of sharing information with siblings, and weighed up the risks and benefits of bringing siblings into PICU. Parents also recounted a number of challenges and facilitators to a positive sibling experience in PICU, including supportive staff and fun activities. Finally, parents, identified that siblings require ongoing support after their inclusion in PICU and made suggestions for ongoing availability of information and supportive resources. CONCLUSIONS: This study has illuminated key parental experiences when supporting sibling inclusion in PICU before, during and after their visit. By understanding these parental experiences, PICU staff can work with and support parents where needed, helping to achieve a positive sibling inclusion experience. IMPLICATIONS FOR CLINICAL PRACTICE: Parents need ongoing support to explain the PICU to siblings of critically ill children and may benefit from specific visual resources to aid communication. In addition, PICUs should aim to ensure the physical layout is supportive of sibling needs, with dedicated spaces for siblings to play and take time out during their experience.

Coral Gardens Reef, Belize: An Acropora spp. refugium under threat in a warming world.

Live coral cover has declined precipitously on Caribbean reefs in recent decades. Acropora cervicornis coral has been particularly decimated, and few Western Atlantic Acropora spp. refugia remain. Coral Gardens, Belize, was identified in 2020 as a long-term refugium for this species. This study assesses changes in live A. cervicornis coral abundance over time at Coral Gardens to monitor the stability of A. cervicornis corals, and to explore potential threats to this important refugium. Live coral cover was documented annually from 2012-2019 along five permanent transects. In situ sea-surface temperature data were collected at Coral Gardens throughout the study period and compared with calibrated satellite data to calculate Maximum Monthly Mean (MMM) temperatures and Degree Heating Weeks (DHW). Data on bathymetry, sediment, substrate, herbivore abundance, and macroalgal abundance were collected in 2014 and 2019 to assess potential threats to Coral Gardens. Live coral cover declined at all five transect sites over the study period. The greatest loss of live coral occurred between 2016 and 2017, coincident with the earliest and highest maximum average temperatures recorded at the study site, and the passage of a hurricane in 2016. Structural storm damage was not observed at Coral Gardens, though live coral cover declined after the passage of the storm. Uranium-thorium (230Th) dating of 26 dead in situ fragments of A. cervicornis collected in 2015 from Coral Gardens revealed no correlation between coral mortality and tropical storms and hurricanes in the recent past. Our data suggest that several other common drivers for coral decline (i.e. herbivory, predation, sedimentation, pH) may likely be ruled out for Coral Gardens. At the end of the study period, Coral Gardens satisfied most criteria for refugium status. However, the early onset, higher mean, and longer duration of above-average temperatures, as well as intermittent temperature anomalies likely played a critical role in the stability of this refugium. We suggest that temperature stress in 2016 and perhaps 2015 may have increased coral tissue vulnerability at Coral Gardens to a passing hurricane, threatening the status of this unique refugium.

Coral Gardens Reef, Belize: A refugium in the face of Caribbean-wide Acropora spp. coral decline.

Caribbean Acropora spp. corals have undergone a decline in cover since the second half of the twentieth century. Loss of these architecturally complex and fast-growing corals has resulted in significant, cascading changes to the character, diversity, and available eco-spaces of Caribbean reefs. Few thriving Acropora spp. populations exist today in the Caribbean and western North Atlantic seas, and our limited ability to access data from reefs assessed via long-term monitoring efforts means that reef scientists are challenged to determine resilience and longevity of existing Acropora spp. reefs. Here we used multiple dating methods to measure reef longevity and determine whether Coral Gardens Reef, Belize, is a refuge for Acropora cervicornis against the backdrop of wider Caribbean decline. We used a new genetic-aging technique to identify sample sites, and radiocarbon and high-precision uranium-thorium (U-Th) dating techniques to test whether one of the largest populations of extant A. cervicornis in the western Caribbean is newly established after the 1980s, or represents a longer-lived, stable population. We did so with respect for ethical sampling of a threatened species. Our data show corals ranging in age from 1910 (14C) or 1915 (230Th) to at least November 2019. While we cannot exclude the possibility of short gaps in the residence of A. cervicornis earlier in the record, the data show consistent and sustained living coral throughout the 1980s and up to at least 2019. We suggest that Coral Gardens has served as a refuge for A. cervicornis and that identifying other, similar sites may be critical to efforts to grow, preserve, conserve, and seed besieged Caribbean reefs.

Exploring the use of Immersive Virtual Reality to enhance Psychological Well-Being in Pediatric Oncology: A pilot randomized controlled trial.

PURPOSE: To investigate whether Immersive Virtual Reality (VR) has a greater positive influence on oncology patients' physical and emotional mood states when compared to an iPad attentional control condition. Our secondary objective was to understand what factors influenced VR effectiveness. METHOD: Participants were 90 oncology inpatients, aged 7-19 years, and their primary parent caregiver. Using a randomized controlled study design patients were allocated to VR (three content groups) or an iPad control condition. Pre-post-intervention self-report state measures were collected using visual analogue scales and an objective measure of physiological arousal (pulse rate). Post-intervention, patients reported on level of immersion, enjoyment and simulator sickness. RESULTS: Patients benefited from both Immersive VR and novel iPad intervention with no statistically significant differences found between conditions on child outcomes. However, patients accessing Immersive VR consistently reported greater positive shifts in mood state and reductions in negative symptoms when compared with iPad. No change was observed in physiological arousal levels (pulse rate) in either condition before, during or immediately after intervention. Moderation analysis showed that the degree of child illness (PedsQL), sex, age, and level of immersion were important in influencing the magnitude of differences between the VR and iPad conditions on mood, anxiety and pain. CONCLUSIONS: These preliminary findings support the use of Immersive VR in clinical oncology settings to improve patient well-being. Further studies examining the application of Immersive VR in supporting children adjusting to hospitalization and cancer treatment are therefore warranted. Factors found to moderate VR effectiveness provide important clinical implications.

National Newborn Screening for cystic fibrosis in the Republic of Ireland: genetic data from the first 6.5 years.

Cystic fibrosis (CF) is the most common life-limiting autosomal recessive disease in the Republic of Ireland (ROI), with a previously quoted incidence of 1 in 1353 and carrier rate of 1 in 19. The National Newborn Screening (NBS) for CF was incorporated in July 2011 in the ROI. A cut-off point of the top 1% Immunoreactive Trypsinogen (IRT) was taken as an indication for 38 CFTR variant panel to maximise identification of affected CF cases and to minimise detection of carriers. All neonates from July 2011 to Dec 2017 with an elevated IRT on NBS were tested with 38 CFTR mutation panel and included. Clinical and laboratory database were analysed. In the first 6.5 years a total of 5,053 newborns (1.16% of total births) were screened with 38 CFTR panel. 170 CF affected cases, 320 unaffected carriers, 32 CF Screening Positive Inconclusive Diagnosis (CFSPID) were identified. There was one missed diagnosis. The most common disease-causing variant was c.1521_1523delCTT (p.(Phe508del)) followed by c.1652G>A (p.(Gly551Asp)). 95 out of 170 (55%) affected newborns were homozygous for c.1521_1523delCTT (p.(Phe08del)) and 25 (15%) carried at least one copy of c.1652G>A (p.(Gly551Asp)). Hence, 70% of affected newborns were eligible for CFTR modulator treatment. The NBS programme has identified almost triple the number of affected newborn with c.1652G>A (p.(Gly551Asp)) than previously quoted figures and identified less than 50% of carriers than predicted. The revised incidence and carrier frequency of CF in the ROI is 1 in 2570 and 1 in 25, respectively.

Feasibility, Acceptability, and Clinical Implementation of an Immersive Virtual Reality Intervention to Address Psychological Well-Being in Children and Adolescents With Cancer.

Objective: Virtual reality (VR), a novel and highly immersive technology, offers promise in addressing potential psychological impacts of cancer treatments and hospitalization. The primary aim of this study was to examine multiple key user perspectives on the acceptability and feasibility of an Immersive VR therapeutic intervention for use with hospitalized patients with cancer. Secondary aims were to identify issues and opportunities related to the adoption and clinical implementation of VR in pediatric oncology settings. Method: The study was conducted at The Royal Children's Hospital (RCH), Melbourne, Australia. Thirty multidisciplinary oncology health care professionals participated in an initial test of VR intervention usability (Stage 1). Ninety oncology inpatients (7-19 years) and their parent caregivers participated in a pilot randomized controlled study to examine the effectiveness of an Immersive VR therapeutic intervention (Stage 2). This mixed methods study reports Stages 1 and 2 quantitative and qualitative data related to VR feasibility and acceptability. Results: Results indicate favorable perceptions from health care professionals with respect to ease of use and usefulness of VR, and had positive intentions to use it in the future. Parent caregivers reported high acceptability of VR for their hospitalized child. Patients reported high satisfaction of the VR intervention within minimal adverse effects. Barriers and facilitators to VR use with seriously ill children and specific recommendations for content development were elicited. Conclusion: This study shows that there are several potential clinical uses for Immersive VR intervention, beyond medical procedural distraction, to support psychological adjustment to hospitalization and patient quality of life.

Dating the skull from Broken Hill, Zambia, and its position in human evolution.

The cranium from Broken Hill (Kabwe) was recovered from cave deposits in 1921, during metal ore mining in what is now Zambia1. It is one of the best-preserved skulls of a fossil hominin, and was initially designated as the type specimen of Homo rhodesiensis, but recently it has often been included in the taxon Homo heidelbergensis2-4. However, the original site has since been completely quarried away, and-although the cranium is often estimated to be around 500 thousand years old5-7-its unsystematic recovery impedes its accurate dating and placement in human evolution. Here we carried out analyses directly on the skull and found a best age estimate of 299 ± 25 thousand years (mean ± 2σ). The result suggests that later Middle Pleistocene Africa contained multiple contemporaneous hominin lineages (that is, Homo sapiens8,9, H. heidelbergensis/H. rhodesiensis and Homo naledi10,11), similar to Eurasia, where Homo neanderthalensis, the Denisovans, Homo floresiensis, Homo luzonensis and perhaps also Homo heidelbergensis and Homo erectus12 were found contemporaneously. The age estimate also raises further questions about the mode of evolution of H. sapiens in Africa and whether H. heidelbergensis/H. rhodesiensis was a direct ancestor of our species13,14.

"He Bore it Like a Scarlet Letter": Medical Student Reflections on Substance Use Disorders.

OBJECTIVE: Substance abuse in the context of the opioid crisis presents a major public health concern. Despite some evidence that medical students' attitudes towards substance use disorders worsen during medical school, very few studies have examined how students' early clinical experiences with substance use disorders shape their views of this clinical population. This study uses student reflective essays to explore these formative educational experiences. METHODS: Using content analysis, the authors analyzed a collection of 802 medical student reflective essays written during core clerkships (excluding Psychiatry), coding for ethical and professional themes as well as descriptions of substance use disorders. In addition to the qualitative identification of themes, the authors used chi-square analysis to determine which themes had statistically significant associations with substance use disorders. RESULTS: Fifty-three essays described patients with substance use disorders. The most common substances described were opioids (n = 25), alcohol (n = 18), and cocaine (n = 11). There were five themes statistically associated with substance use disorders (p < 0.05): (1) adequate treatment, (2) pain, (3) difficult patient, (4) jumping to conclusions, and (5) malingering. CONCLUSIONS: In the sample, students found the treatment of pain to be a significant ethical challenge related to substance use disorders. In considering a comprehensive educational plan, medical educators may need to consider educational venues outside of the Psychiatry clerkship to address substance use disorders.

Identification of a novel cystic fibrosis mutation in three patients of South Asian descent.

INTRODUCTION: The cystic fibrosis (CF) clinical profile and associated CFTR mutation spectrum is poorly understood in the South Asian population. This is likely due to the lack of diagnostic resources and the absence of a centralised CF database and screening programme, despite a relatively large proportion of the global population. METHODS: Following identification of a previously unreported CFTR mutation (c.2805_2810delinsTCAGA; p.(Pro936Ginfs*6)) in a newly diagnosed patient of Indian descent, we interrogated national registries for other cases. RESULTS: We identified three European-born subjects of South Asian descent with CF due to a novel CFTR mutation. All three subjects presented in infancy and each had a severe phenotype with intestinal complications as a presenting feature. Two subjects were diagnosed prior to the advent of universal screening. Preliminary genetic screening failed to identify the causative mutation in all three patients. CONCLUSION: Our work highlights the value of extended or targeted genotyping in selected populations. It also demonstrates the benefit of routine collaboration between national registries. This will promote the identification of novel mutations; leading to greater understanding of genotype-phenotype associations, improved individual prognostication and ultimately the improved availability of novel precision therapies. This collaboration is essential if we are to achieve health equality for people with CF living in resource-limited settings.

Managing uncertainty in inherited cardiac pathologies-an international multidisciplinary survey.

Multi-gene testing is useful in genetically heterogeneous conditions, including inherited cardiac pathologies. Increasing the number of genes analysed increases diagnostic yield of variants of certain, likely, or uncertain pathogenicity. Concerns exist regarding management of variants of uncertain/likely pathogenicity in conditions of oligogenic inheritance or variable expressivity. We surveyed a sample of colleagues across different specialties and departments internationally to compare management of patients with class 3 or class 4 variants in genes associated with non-syndromic cardiomyopathy or arrhythmia. An electronic survey regarding clinical management of variants ( www.surveymonkey.com/r/cardiacvariants ) was designed and distributed to colleagues internationally via professional bodies and direct email. 150 respondents (88 centres, 27 countries) completed the survey, most of whom were Clinical Geneticists or Genetic Counsellors. Most respondents offer pre-symptomatic testing to asymptomatic relatives of an individual with class 4 or class 5 variants. A minority of respondents offer pre-symptomatic testing for class 3 variants. Considering class 4 variants, 22 (15%) are fully reassuring that the patient with a negative predictive test would not develop the familial phenotype, while 123 (82%) counselled patients about the possibility of variant reclassification. Variability existed between and within centres and specialties. Multiple "free text" comments were provided. Recurring themes including need for multidisciplinary input, technical concerns, and concern regarding duty to review variants of uncertain significance. This study demonstrates that variability in management of likely pathogenic/uncertain variants exists. Close multi-disciplinary input is essential. The development of disorder or gene-specific evidence-based guidelines might ameliorate uncertainty in management.

Seasonal to decadal scale influence of environmental drivers on Ba/Ca and Y/Ca in coral aragonite from the southern Great Barrier Reef.

Extensive catchment modification since European settlement on the eastern coast of Australia results in poor coastal water quality, which poses a major threat for near shore coral communities in the iconic Great Barrier Reef (GBR). Long lived inshore corals have the potential to provide long-term temporal records of changing water quality both pre- and post-anthropogenic modification. However, water quality proxies require more study and validation of the robustness of coral-hosted geochemical proxies for a specific site is critical. This study investigated the long-term (1958-2010) influence of environmental drivers on high-resolution Ba/Ca and Y/Ca proxies obtained from Porites sp. coral from Great Keppel Island, southern GBR, Australia. Geochemical proxy records were influenced by environmental change on a seasonal to decadal scale. Although seasonal oscillations of Ba/Ca and Y/Ca were related to rainfall and discharge from the Fitzroy River catchment, some uncorrelated anomalous peaks were evident throughout the time series. Regardless, the behaviour of these proxies was significantly consistent over the longer time scale. Most long-term drought-breaking floods, including one that occurred in winter, resulted in significant increase in the targeted elemental ratios owing to higher terrigenous sediment flux to the near shore marine environment from a catchment with reduced groundcover. Following this intense flushing event, elemental ratios were reduced in subsequent wet periods as a result of less sediment being available for transport to coastal seawater. Ba/Ca and Y/Ca proxies can be valuable tools in reconstructing multiyear variations in terrestrial runoff and associated inshore water quality. As these proxies and their regional and local controls are better understood they will aid our understanding of how reefs have responded and may respond to changing water conditions.

DIALS: implementation and evaluation of a new integration package.

The DIALS project is a collaboration between Diamond Light Source, Lawrence Berkeley National Laboratory and CCP4 to develop a new software suite for the analysis of crystallographic X-ray diffraction data, initially encompassing spot finding, indexing, refinement and integration. The design, core algorithms and structure of the software are introduced, alongside results from the analysis of data from biological and chemical crystallography experiments.

Erratum: Expanding Lorentz and spectrum corrections to large volumes of reciprocal space for single-crystal time-of-flight neutron diffraction. Corrigendum.

[This corrects the article DOI: 10.1107/S1600576716001369.].

U-Th dating reveals regional-scale decline of branching Acropora corals on the Great Barrier Reef over the past century.

Hard coral cover on the Great Barrier Reef (GBR) is on a trajectory of decline. However, little is known about past coral mortality before the advent of long-term monitoring (circa 1980s). Using paleoecological analysis and high-precision uranium-thorium (U-Th) dating, we reveal an extensive loss of branching Acropora corals and changes in coral community structure in the Palm Islands region of the central GBR over the past century. In 2008, dead coral assemblages were dominated by large, branching Acropora and living coral assemblages by genera typically found in turbid inshore environments. The timing of Acropora mortality was found to be occasionally synchronous among reefs and frequently linked to discrete disturbance events, occurring in the 1920s to 1960s and again in the 1980s to 1990s. Surveys conducted in 2014 revealed low Acropora cover (<5%) across all sites, with very little evidence of change for up to 60 y at some sites. Collectively, our results suggest a loss of resilience of this formerly dominant key framework builder at a regional scale, with recovery severely lagging behind predictions. Our study implies that the management of these reefs may be predicated on a shifted baseline.

High-speed fixed-target serial virus crystallography.

We report a method for serial X-ray crystallography at X-ray free-electron lasers (XFELs), which allows for full use of the current 120-Hz repetition rate of the Linear Coherent Light Source (LCLS). Using a micropatterned silicon chip in combination with the high-speed Roadrunner goniometer for sample delivery, we were able to determine the crystal structures of the picornavirus bovine enterovirus 2 (BEV2) and the cytoplasmic polyhedrosis virus type 18 polyhedrin, with total data collection times of less than 14 and 10 min, respectively. Our method requires only micrograms of sample and should therefore broaden the applicability of serial femtosecond crystallography to challenging projects for which only limited sample amounts are available. By synchronizing the sample exchange to the XFEL repetition rate, our method allows for most efficient use of the limited beam time available at XFELs and should enable a substantial increase in sample throughput at these facilities.

Drop-on-demand sample delivery for studying biocatalysts in action at X-ray free-electron lasers.

X-ray crystallography at X-ray free-electron laser sources is a powerful method for studying macromolecules at biologically relevant temperatures. Moreover, when combined with complementary techniques like X-ray emission spectroscopy, both global structures and chemical properties of metalloenzymes can be obtained concurrently, providing insights into the interplay between the protein structure and dynamics and the chemistry at an active site. The implementation of such a multimodal approach can be compromised by conflicting requirements to optimize each individual method. In particular, the method used for sample delivery greatly affects the data quality. We present here a robust way of delivering controlled sample amounts on demand using acoustic droplet ejection coupled with a conveyor belt drive that is optimized for crystallography and spectroscopy measurements of photochemical and chemical reactions over a wide range of time scales. Studies with photosystem II, the phytochrome photoreceptor, and ribonucleotide reductase R2 illustrate the power and versatility of this method.

Prehistorical and historical declines in Caribbean coral reef accretion rates driven by loss of parrotfish.

Caribbean coral reefs have transformed into algal-dominated habitats over recent decades, but the mechanisms of change are unresolved due to a lack of quantitative ecological data before large-scale human impacts. To understand the role of reduced herbivory in recent coral declines, we produce a high-resolution 3,000 year record of reef accretion rate and herbivore (parrotfish and urchin) abundance from the analysis of sediments and fish, coral and urchin subfossils within cores from Caribbean Panama. At each site, declines in accretion rates and parrotfish abundance were initiated in the prehistorical or historical period. Statistical tests of direct cause and effect relationships using convergent cross mapping reveal that accretion rates are driven by parrotfish abundance (but not vice versa) but are not affected by total urchin abundance. These results confirm the critical role of parrotfish in maintaining coral-dominated reef habitat and the urgent need for restoration of parrotfish populations to enable reef persistence.

Structure of photosystem II and substrate binding at room temperature.

Light-induced oxidation of water by photosystem II (PS II) in plants, algae and cyanobacteria has generated most of the dioxygen in the atmosphere. PS II, a membrane-bound multi-subunit pigment protein complex, couples the one-electron photochemistry at the reaction centre with the four-electron redox chemistry of water oxidation at the Mn4CaO5 cluster in the oxygen-evolving complex (OEC). Under illumination, the OEC cycles through five intermediate S-states (S0 to S4), in which S1 is the dark-stable state and S3 is the last semi-stable state before O-O bond formation and O2 evolution. A detailed understanding of the O-O bond formation mechanism remains a challenge, and will require elucidation of both the structures of the OEC in the different S-states and the binding of the two substrate waters to the catalytic site. Here we report the use of femtosecond pulses from an X-ray free electron laser (XFEL) to obtain damage-free, room temperature structures of dark-adapted (S1), two-flash illuminated (2F; S3-enriched), and ammonia-bound two-flash illuminated (2F-NH3; S3-enriched) PS II. Although the recent 1.95 Å resolution structure of PS II at cryogenic temperature using an XFEL provided a damage-free view of the S1 state, measurements at room temperature are required to study the structural landscape of proteins under functional conditions, and also for in situ advancement of the S-states. To investigate the water-binding site(s), ammonia, a water analogue, has been used as a marker, as it binds to the Mn4CaO5 cluster in the S2 and S3 states. Since the ammonia-bound OEC is active, the ammonia-binding Mn site is not a substrate water site. This approach, together with a comparison of the native dark and 2F states, is used to discriminate between proposed O-O bond formation mechanisms.

Advances in X-ray free electron laser (XFEL) diffraction data processing applied to the crystal structure of the synaptotagmin-1 / SNARE complex.

X-ray free electron lasers (XFELs) reduce the effects of radiation damage on macromolecular diffraction data and thereby extend the limiting resolution. Previously, we adapted classical post-refinement techniques to XFEL diffraction data to produce accurate diffraction data sets from a limited number of diffraction images (Uervirojnangkoorn et al., 2015), and went on to use these techniques to obtain a complete data set from crystals of the synaptotagmin-1 / SNARE complex and to determine the structure at 3.5 Å resolution (Zhou et al., 2015). Here, we describe new advances in our methods and present a reprocessed XFEL data set of the synaptotagmin-1 / SNARE complex. The reprocessing produced small improvements in electron density maps and the refined atomic model. The maps also contained more information than those of a lower resolution (4.1 Å) synchrotron data set. Processing a set of simulated XFEL diffraction images revealed that our methods yield accurate data and atomic models.