Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 27
Filter
Add more filters

Publication year range
1.
Nature ; 580(7803): 372-375, 2020 04.
Article in English | MEDLINE | ID: mdl-32296179

ABSTRACT

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.


Subject(s)
Biological Evolution , Hominidae , Skull , Animals , Fossils , Time Factors
2.
Pediatr Crit Care Med ; 25(5): e258-e262, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38695704

ABSTRACT

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.


Subject(s)
Intensive Care Units, Pediatric , Privacy , Terminal Care , Humans , Terminal Care/ethics , Terminal Care/psychology , Intensive Care Units, Pediatric/organization & administration , Child , Professional-Family Relations , Family/psychology
3.
Nature ; 539(7627): 43-47, 2016 11 03.
Article in English | MEDLINE | ID: mdl-27680699

ABSTRACT

BinAB is a naturally occurring paracrystalline larvicide distributed worldwide to combat the devastating diseases borne by mosquitoes. These crystals are composed of homologous molecules, BinA and BinB, which play distinct roles in the multi-step intoxication process, transforming from harmless, robust crystals, to soluble protoxin heterodimers, to internalized mature toxin, and finally to toxic oligomeric pores. The small size of the crystals-50 unit cells per edge, on average-has impeded structural characterization by conventional means. Here we report the structure of Lysinibacillus sphaericus BinAB solved de novo by serial-femtosecond crystallography at an X-ray free-electron laser. The structure reveals tyrosine- and carboxylate-mediated contacts acting as pH switches to release soluble protoxin in the alkaline larval midgut. An enormous heterodimeric interface appears to be responsible for anchoring BinA to receptor-bound BinB for co-internalization. Remarkably, this interface is largely composed of propeptides, suggesting that proteolytic maturation would trigger dissociation of the heterodimer and progression to pore formation.


Subject(s)
Bacillus/chemistry , Bacterial Toxins/chemistry , Culicidae , Insecticides/chemistry , Larva , Lasers , Animals , Binding Sites , Crystallization , Crystallography, X-Ray , Culicidae/metabolism , Hydrogen-Ion Concentration , Larva/chemistry , Larva/metabolism , Models, Molecular , Protein Multimerization , Proteolysis , Tyrosine/chemistry
4.
Nature ; 540(7633): 453-457, 2016 12 15.
Article in English | MEDLINE | ID: mdl-27871088

ABSTRACT

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.


Subject(s)
Cyanobacteria/chemistry , Electrons , Lasers , Photosystem II Protein Complex/chemistry , Photosystem II Protein Complex/metabolism , Temperature , Ammonia/chemistry , Ammonia/metabolism , Bacterial Proteins/chemistry , Bacterial Proteins/metabolism , Binding Sites , Crystallization , Manganese/metabolism , Models, Molecular , Oxygen/metabolism , Substrate Specificity , Water/metabolism
5.
Nat Methods ; 14(8): 805-810, 2017 Aug.
Article in English | MEDLINE | ID: mdl-28628129

ABSTRACT

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.


Subject(s)
Algorithms , Crystallography, X-Ray/methods , Image Enhancement/methods , Image Interpretation, Computer-Assisted/methods , Imaging, Three-Dimensional/methods , Viruses/ultrastructure , Reproducibility of Results , Sample Size , Sensitivity and Specificity
6.
Nat Methods ; 14(4): 443-449, 2017 Apr.
Article in English | MEDLINE | ID: mdl-28250468

ABSTRACT

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.


Subject(s)
Crystallography, X-Ray/methods , Lasers , Acoustics , Photosystem II Protein Complex/chemistry , Phytochrome/chemistry , Ribonucleotide Reductases/chemistry , Spectrometry, X-Ray Emission/methods
7.
Proc Natl Acad Sci U S A ; 114(39): 10350-10355, 2017 09 26.
Article in English | MEDLINE | ID: mdl-28893981

ABSTRACT

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.


Subject(s)
Anthozoa/growth & development , Coral Reefs , Environmental Monitoring/methods , Global Warming , Radiometric Dating/methods , Animals , Australia , Thorium/chemistry , Uranium/chemistry
8.
Acad Psychiatry ; 44(2): 122-128, 2020 Apr.
Article in English | MEDLINE | ID: mdl-32048175

ABSTRACT

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.


Subject(s)
Clinical Clerkship , Problem-Based Learning , Students, Medical/psychology , Substance-Related Disorders , Writing , Alcohol Drinking/adverse effects , Education, Medical, Undergraduate , Female , Humans , Male , Malingering/psychology , Opiate Alkaloids/adverse effects , Substance-Related Disorders/psychology , Substance-Related Disorders/therapy
9.
Nat Methods ; 13(1): 59-62, 2016 Jan.
Article in English | MEDLINE | ID: mdl-26619013

ABSTRACT

We describe a concentric-flow electrokinetic injector for efficiently delivering microcrystals for serial femtosecond X-ray crystallography analysis that enables studies of challenging biological systems in their unadulterated mother liquor. We used the injector to analyze microcrystals of Geobacillus stearothermophilus thermolysin (2.2-Å structure), Thermosynechococcus elongatus photosystem II (<3-Å diffraction) and Thermus thermophilus small ribosomal subunit bound to the antibiotic paromomycin at ambient temperature (3.4-Å structure).


Subject(s)
Crystallography/methods , Photosystem II Protein Complex/metabolism , Ribosomes/metabolism , Models, Molecular
10.
Intensive Crit Care Nurs ; 83: 103696, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38608616

ABSTRACT

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.


Subject(s)
Intensive Care Units, Pediatric , Parents , Qualitative Research , Siblings , Humans , Intensive Care Units, Pediatric/organization & administration , Parents/psychology , Male , Female , Siblings/psychology , Australia , Child , Child, Preschool , Adult , Infant , Interviews as Topic/methods
11.
Proc Biol Sci ; 280(1750): 20122100, 2013 Jan 07.
Article in English | MEDLINE | ID: mdl-23135672

ABSTRACT

The inshore reefs of the Great Barrier Reef (GBR) have undergone significant declines in water quality following European settlement (approx. 1870 AD). However, direct evidence of impacts on coral assemblages is limited by a lack of historical baselines prior to the onset of modern monitoring programmes in the early 1980s. Through palaeoecological reconstructions, we report a previously undocumented historical collapse of Acropora assemblages at Pelorus Island (central GBR). High-precision U-series dating of dead Acropora fragments indicates that this collapse occurred between 1920 and 1955, with few dates obtained after 1980. Prior to this event, our results indicate remarkable long-term stability in coral community structure over centennial scales. We suggest that chronic increases in sediment flux and nutrient loading following European settlement acted as the ultimate cause for the lack of recovery of Acropora assemblages following a series of acute disturbance events (SST anomalies, cyclones and flood events). Evidence for major degradation in reef condition owing to human impacts prior to modern ecological surveys indicates that current monitoring of inshore reefs on the GBR may be predicated on a significantly shifted baseline.


Subject(s)
Anthozoa/physiology , Coral Reefs , Human Activities , Water Pollutants, Chemical/toxicity , Animals , Environmental Monitoring , Geologic Sediments/analysis , Humans , Population Dynamics , Queensland , Water Movements
12.
PLoS One ; 18(2): e0280852, 2023.
Article in English | MEDLINE | ID: mdl-36753468

ABSTRACT

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.


Subject(s)
Anthozoa , Refugium , Animals , Gardens , Belize , Coral Reefs
13.
Cytotherapy ; 12(7): 853-6, 2010 Nov.
Article in English | MEDLINE | ID: mdl-20942603

ABSTRACT

The last decade has seen a dramatic rise in the development of new cellular therapeutics in a wide range of indications. There have been acceptable safety profiles reported in early studies using blood-derived and adherent stem cell products, but also an inconsistent efficacy record. Further expansion has been hindered in part by a lack of capital (both private and public) and delayed entry into the cell therapy space by large healthcare and pharmaceutical companies, those members of the industry most reliably able to initiate and maintain advanced-phase clinical trials. With recognition that the International Society for Cellular Therapy (ISCT) is uniquely positioned to serve the global translational regenerative medicine research community as a network hub for scientific standards and policy, the ISCT commissioned the establishment of an Industry Task Force (ITF) to address current and future roles for industry. The objectives of the ITF were to gather information and prioritize efforts for a new Commercialization Committee (CC) and to construct innovative platforms that would foster constructive and synergistic collaborations between industry and ISCT. Recommendations and conclusions of the ITF included that the new CC: (1) foster new relationships with therapeutic and stem cell societies, (2) foster educational workshops and forums to cross-educate and standardize practices, (3) create industry subcommittees to address priority initiatives, with clear benchmarks and global implementation, and (4) establish a framework for a greater industry community within ISCT, opening doors for industry to share the new vision for commercialization of cell therapy, emphasizing the regenerative medicine space.


Subject(s)
Cell- and Tissue-Based Therapy , Clinical Trials as Topic , Drug Industry , Commerce , Humans , Practice Guidelines as Topic , Regenerative Medicine , Societies, Scientific , Translational Research, Biomedical
14.
J Pediatr Oncol Nurs ; 37(4): 265-277, 2020.
Article in English | MEDLINE | ID: mdl-32536320

ABSTRACT

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.


Subject(s)
Neoplasms/therapy , Virtual Reality Exposure Therapy/methods , Virtual Reality , Adolescent , Australia , Child , Feasibility Studies , Female , Humans , Male , Neoplasms/psychology , Outcome and Process Assessment, Health Care , Pilot Projects , Quality of Life , User-Computer Interface
15.
PLoS One ; 15(9): e0239267, 2020.
Article in English | MEDLINE | ID: mdl-32997690

ABSTRACT

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.


Subject(s)
Anthozoa/physiology , Conservation of Natural Resources , Coral Reefs , Refugium , Animals , Belize , Caribbean Region , Endangered Species , Population Dynamics
16.
Eur J Oncol Nurs ; 48: 101804, 2020 Oct.
Article in English | MEDLINE | ID: mdl-32949941

ABSTRACT

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.


Subject(s)
Anxiety Disorders/therapy , Medical Oncology/standards , Oncology Nursing/standards , Pediatrics/standards , Practice Guidelines as Topic , Stress, Psychological/therapy , Virtual Reality Exposure Therapy/standards , Adolescent , Adult , Child , Child, Preschool , Female , Humans , Male , Pilot Projects , Young Adult
17.
Clin Respir J ; 14(6): 586-588, 2020 Jun.
Article in English | MEDLINE | ID: mdl-32043836

ABSTRACT

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.


Subject(s)
Asian People/genetics , Cystic Fibrosis Transmembrane Conductance Regulator/genetics , Cystic Fibrosis/genetics , Adolescent , Adult , Cystic Fibrosis/complications , Cystic Fibrosis/diagnosis , Cystic Fibrosis/pathology , Exocrine Pancreatic Insufficiency/diagnosis , Exocrine Pancreatic Insufficiency/etiology , Female , Genetic Association Studies , Genetic Testing/standards , Genotype , Humans , Infant , Intestinal Obstruction/diagnosis , Intestinal Obstruction/etiology , Intestinal Obstruction/surgery , Male , Meconium Ileus/diagnosis , Meconium Ileus/etiology , Meconium Ileus/surgery , Mutation , Phenotype , Sweat/chemistry
18.
Eur J Hum Genet ; 28(12): 1669-1674, 2020 12.
Article in English | MEDLINE | ID: mdl-32483343

ABSTRACT

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.


Subject(s)
Cystic Fibrosis Transmembrane Conductance Regulator/genetics , Cystic Fibrosis/genetics , Genetic Testing/statistics & numerical data , Neonatal Screening/standards , Cystic Fibrosis/diagnosis , Female , Gene Frequency , Genetic Testing/standards , Heterozygote , Humans , Infant, Newborn , Ireland , Male , Mutation , Sensitivity and Specificity
19.
Eur J Hum Genet ; 27(8): 1178-1185, 2019 08.
Article in English | MEDLINE | ID: mdl-30979968

ABSTRACT

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.


Subject(s)
Arrhythmias, Cardiac/genetics , Cardiomyopathies/genetics , Genetic Predisposition to Disease/genetics , Genetic Testing/methods , Genetic Variation , Surveys and Questionnaires , Arrhythmias, Cardiac/diagnosis , Arrhythmias, Cardiac/therapy , Cardiomyopathies/diagnosis , Cardiomyopathies/therapy , Humans , Interdisciplinary Communication , Internationality , Reproducibility of Results , Uncertainty , Whole Genome Sequencing/methods
20.
Sci Total Environ ; 639: 1099-1109, 2018 Oct 15.
Article in English | MEDLINE | ID: mdl-29929279

ABSTRACT

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.


Subject(s)
Anthozoa/physiology , Calcium Carbonate/analysis , Coral Reefs , Environmental Monitoring , Animals , Australia , Islands , Seasons
SELECTION OF CITATIONS
SEARCH DETAIL