Nearly all the sky is covered by Lyman-α emission around high-redshift galaxies.

Galaxies are surrounded by large reservoirs of gas, mostly hydrogen, that are fed by inflows from the intergalactic medium and by outflows from galactic winds. Absorption-line measurements along the lines of sight to bright and rare background quasars indicate that this circumgalactic medium extends far beyond the starlight seen in galaxies, but very little is known about its spatial distribution. The Lyman-α transition of atomic hydrogen at a wavelength of 121.6 nanometres is an important tracer of warm (about 104 kelvin) gas in and around galaxies, especially at cosmological redshifts greater than about 1.6 at which the spectral line becomes observable from the ground. Tracing cosmic hydrogen through its Lyman-α emission has been a long-standing goal of observational astrophysics1-3, but the extremely low surface brightness of the spatially extended emission is a formidable obstacle. A new window into circumgalactic environments was recently opened by the discovery of ubiquitous extended Lyman-α emission from hydrogen around high-redshift galaxies4,5. Such measurements were previously limited to especially favourable systems6-8 or to the use of massive statistical averaging9,10 because of the faintness of this emission. Here we report observations of low-surface-brightness Lyman-α emission surrounding faint galaxies at redshifts between 3 and 6. We find that the projected sky coverage approaches 100 per cent. The corresponding rate of incidence (the mean number of Lyman-α emitters penetrated by any arbitrary line of sight) is well above unity and similar to the incidence rate of high-column-density absorbers frequently detected in the spectra of distant quasars11-14. This similarity suggests that most circumgalactic atomic hydrogen at these redshifts has now been detected in emission.

Author Correction: Nearly all the sky is covered by Lyman-α emission around high-redshift galaxies.

Change history: In this Letter, author M. Akhlaghi should be associated with affiliation (2) rather than (3). This error has been corrected online.

Understanding the needs and preferences for cancer care among First Nations people: An integrative review.

AIM: This systematic review aimed to identify the needs and preferences for cancer care services among Australian First Nations people. DESIGN: Integrative review. DATA SOURCES: An integrative review was conducted. A wide range of search terms were used to increase the sensitivity and specificity of the searches in electronic databases. Methodological quality assessment, data extraction, was conducted independently by two reviewers, and a narrative synthesis was conducted. RESULTS: Forty-two studies were included. A total of 2965 Australian First Nations adults, both men and women of various ages across the lifespan, were represented; no First Nations children affected by cancer were represented in the studies. Three themes emerged which included: (1) discrimination, racism and trauma, resulting from colonization, directly impacted First National people's cancer care experience; (2) cultural ways of knowing, being and doing are fundamental to how First Nations people engage with cancer care services; and (3) First Nations people need culturally safe person-centred cancer care services that address practical needs. CONCLUSION: Most participants represented in this review experienced discrimination, racism and trauma, resulting from colonization, which directly negatively impacted Aboriginal peoples' cancer care experience. While the Optimal Cancer Pathway (OCP) was launched in Australia several years ago, people with cancer may continue to experience distressing unmet care needs. PATIENT OR PUBLIC CONTRIBUTION: Our team includes both First Nations people, non-First Nations researchers and healthcare professionals with expertise in cancer care. The researchers employed decolonizing restorative approaches to ensure voice, respect, accountability and reciprocity in this review work. IMPLICATIONS FOR NURSING PRACTICE: Members of the multidisciplinary team including nurses and policymakers should reflect on these findings, ensure that they have up-to-date cultural safety training and stand together with Indigenous and non-Indigenous cancer leaders to take proactive steps to stamp out and dismantle oppression in health, and safely implement the OCP.

Therapeutic efficacy of anti-dandruff shampoos: a randomized clinical trial comparing products based on potentiated zinc pyrithione and zinc pyrithione/climbazole.

OBJECTIVES: Dandruff is a chronic, relapsing scalp condition that negatively impacts the quality of life of sufferers. Regular use of anti-fungal shampoos represents a proven therapeutic strategy to improve the most common symptoms of flakes and itch. Two recent approaches for enhancing the efficacy of anti-fungal shampoos are maximizing bio-availability of the active material or the addition of a second active material. Our aim is to compare the therapeutic efficacy of these two approaches - maximization of bio-availability of the zinc pyrithione (ZPT) active material or the combination of ZPT with a secondary active material. METHODS: The anti-fungal potency of shampoos representing each of these approaches was evaluated in vitro using a standard microbiology method. Spatial delivery of ZPT particles in the follicular infundibulum was assessed in vivo using a novel confocal microscopy methodology. Clinical efficacy was assessed in a randomized, double-blind trial involving 620 male and female subjects using scalp flaking and epidermal histamine level as endpoints. RESULTS: The shampoo formula with maximized ZPT bio-availability known as the Potentiated ZPT formula exhibited greater anti-fungal potency than the Dual Active shampoo containing both ZPT and climbazole. The Potentiated ZPT formula also delivered more ZPT to the lower infundibulum than the Dual Active shampoo. A 4-week treatment with the Potentiated ZPT formula resulted in superior clinical efficacy compared with the Dual Active product at all 4 weekly time points for both flaking and epidermal histamine endpoints. CONCLUSION: These results highlight the critical role that the shampoo vehicle plays in realizing full potency of active materials. By optimizing the delivery vehicle, the enhanced anti-fungal potency and the maximized spatial delivery of active materials result in greater symptomatic improvement than a product with two active materials. The therapeutic efficacy of a product based on a complex delivery vehicle such as a shampoo must be considered from a full-product perspective rather than just the active system as the non-active components of the composition will often play a significant role in the overall product pharmacology and resultant efficacy.

To understand the experiences, needs, and preferences for supportive care, among children and adolescents (0-19 years) diagnosed with cancer: a systematic review of qualitative studies.

PURPOSE: This study aimed to understand the experiences, needs, and preferences for supportive care, among children and adolescents (0-19 years) diagnosed with cancer. METHODS: A qualitative systematic review has been reported according to PRISMA guidelines. A comprehensive search was conducted across multiple databases (APA PsycINFO, CINAHL, and Medline) and citation searches. Studies were screened according to pre-determined inclusion and exclusion criteria. Methodological quality was evaluated. Findings were extracted in relation to the context of interest of experiences, needs, and preferences of supportive care. Each finding was accompanied by a qualitative verbatim illustration representing the participant's voice. RESULTS: 4449 publications were screened, and 44 studies were included. Cancer populations represented in the included studies included lymphoma, leukaemia, brain cancer, sarcomas, and neuroblastoma. Two overarching synthesised findings were identified as (1) coping, caring relationships, communication, and impact of the clinical environment, and (2) experiences of isolation, fear of the unknown, restricted information, and changing self. Children and adolescents articulated that cancer care would be enhanced by developing a sense of control over their body and healthcare, being involved in communication and shared decision-making, and ensuring the clinical environment is age-appropriate. Many experienced a sense of disconnection from the rest of the world (including peers, school, and experiences of prejudice and bullying), and a lack of tailored support and information were identified as key unmet care needs that require further intervention. CONCLUSIONS: Children and adolescent who are diagnosed with cancer are a unique and understudied group in oncological survivorship research, with the slowest progress in improvement of care over time. This review will facilitate the development of future interventions and promote the importance of tailored support for children and adolescents at all stages of the cancer journey. IMPLICATIONS FOR CANCER SURVIVORS: Children and adolescents continue to experience a range of difficulties despite routine contact with cancer healthcare professionals. Children and adolescents should be carefully assessed about their individual circumstances and preferences for support given the clear implications from this review that "one size" does not fit all.

What are the experiences of supportive care in people affected by brain cancer and their informal caregivers: A qualitative systematic review.

PURPOSE: To critically synthesise qualitative research to understand experiences of supportive care in people affected by brain cancer and their informal caregivers. METHODS: A qualitative systematic review was conducted according to the Joanna Briggs methodology and has been reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) Guidelines. Electronic databases were searched by an expert systematic review librarian for all qualitative studies irrespective of research design. All publications were double screened by two reviewers using a pre-determined exclusion and inclusion criteria. The review was managed using Covidence systematic review software. Methodological quality assessment and data extraction were performed. Qualitative findings accompanied by illustrative quotes from included studies were extracted and grouped into categories, which created the overall synthesised findings. RESULTS: A total of 33 studies were included which represented a total sample of 671 participants inclusive of 303 patients and 368 informal caregivers. There was a total of 220 individual findings included in this review, which were synthesised into two findings (1) caregivers and patients perceived supports which would have been helpful and (2) caregiver and patient experiences of unmet supportive care needs. CONCLUSION: This review highlighted the suffering and distress caused by brain cancer and associated treatments. Both patients and their informal caregivers experienced disconnect from themselves in renegotiating roles, and a profound sense of loneliness as the physical deterioration of the disease progressed. Both patients and informal caregivers reported similar unmet needs within the current service provision for brain cancer. However, what is apparent is that current cancer services are provided solely for patients, with little or no consideration to the support needs of both the patient and their informal caregiver. Service re-design is needed to improve care coordination with individualised informational support, implementation of holistic needs assessments for both the patients and their caregivers, better community support provision, improved opportunities for emotional care with early referral for palliative care services. IMPLICATIONS FOR CANCER SURVIVORS: It is recommended that members of the multidisciplinary brain cancer team reflect on these findings to target holistic needs assessments and develop shared self-management care plans for both the patient and the informal caregiver.

The discovery of a galaxy-wide superwind from a young massive galaxy at redshift z approximately 3.

High-velocity galactic outflows, driven by intense bursts of star formation and black hole accretion, are processes invoked by current theories of galaxy formation to terminate star formation in the most massive galaxies and to deposit heavy elements in the intergalactic medium. From existing observational evidence (for high-redshift galaxies) it is unclear whether such outflows are localized to regions of intense star formation just a few kiloparsecs in extent, or whether they instead have a significant impact on the entire galaxy and its surroundings. Here we present two-dimensional spectroscopy of a star-forming galaxy at redshift z = 3.09 (seen 11.5 gigayears ago, when the Universe was 20 per cent of its current age): its spatially extended Lyalpha line emission appears to be absorbed by H i in a foreground screen covering the entire galaxy, with a lateral extent of at least 100 kpc and remarkable velocity coherence. This screen was ejected from the galaxy during a starburst several 10(8) years earlier and has subsequently swept up gas from the surrounding intergalactic medium and cooled. This demonstrates the galaxy-wide impact of high-redshift superwinds.

The GTP-binding protein Ypt1 is required for transport in vitro: the Golgi apparatus is defective in ypt1 mutants.

The YPT1 gene encodes a raslike, GTP-binding protein that is essential for growth of yeast cells. We show here that mutations in the ypt1 gene disrupt transport of carboxypeptidase Y to the vacuole in vivo and transport of pro-alpha-factor to a site of extensive glycosylation in the Golgi apparatus in vitro. Two different ypt1 mutations result in loss of function of the Golgi complex without affecting the activity of the endoplasmic reticulum or soluble components required for in vitro transport. The function of the mutant Golgi apparatus can be restored by preincubation with wild-type cytosol. The transport defect observed in vitro cannot be overcome by addition of Ca++ to the reaction mixture. We have also established genetic interactions between ypt1 and a subset of the other genes required for transport to and through the Golgi apparatus.

Isolation of a functional vesicular intermediate that mediates ER to Golgi transport in yeast.

We have used an in vitro assay that reconstitutes transport from the ER to the Golgi complex in yeast to identify a functional vesicular intermediate in transit to the Golgi apparatus. Permeabilized yeast cells, which serve as the donor in this assay, release a homogeneous population of vesicles that are biochemically distinct from the donor ER fraction. The isolated vesicles, containing a post-ER/pre-Golgi form of the marker protein pro-alpha-factor, were able to bind to and fuse with exogenously added Golgi membranes. The ability to isolate fusion competent vesicles provides direct evidence that ER to Golgi membrane transport is mediated by a discrete population of vesicular carriers.

Dictyostelium discoideum mutants with temperature-sensitive defects in endocytosis.

We have isolated and characterized temperature-sensitive endocytosis mutants in Dictyostelium discoideum. Dictyostelium is an attractive model for genetic studies of endocytosis because of its high rates of endocytosis, its reliance on endocytosis for nutrient uptake, and tractable molecular genetics. Endocytosis-defective mutants were isolated by a fluorescence-activated cell sorting (FACS) as cells unable to take up a fluorescent marker. One temperature-sensitive mutant (indy1) was characterized in detail and found to exhibit a complete block in fluid phase endocytosis at the restrictive temperature, but normal rates of endocytosis at the permissive temperature. Likewise, a potential cell surface receptor that was rapidly internalized in wild-type cells and indy1 cells at the permissive temperature was poorly internalized in indy1 under restrictive conditions. Growth was also completely arrested at the restrictive temperature. The endocytosis block was rapidly induced upon shift to the restrictive temperature and reversed upon return to normal conditions. Inhibition of endocytosis was also specific, as other membrane-trafficking events such as phagocytosis, secretion of lysosomal enzymes, and contractile vacuole function were unaffected at the restrictive temperature. Because recycling and transport to late endocytic compartments were not affected, the site of the defect's action is probably at an early step in the endocytic pathway. Additionally, indy1 cells were unable to proceed through the normal development program at the restrictive temperature. Given the tight functional and growth phenotypes, the indy1 mutant provides an opportunity to isolate genes responsible for endocytosis in Dictyostelium by complementation cloning.

Dictyostelium discoideum mutants with conditional defects in phagocytosis.

We have isolated and characterized Dictyostelium discoideum mutants with conditional defects in phagocytosis. Under suspension conditions, the mutants exhibited dramatic reductions in the uptake of bacteria and polystyrene latex beads. The initial binding of these ligands was unaffected, however, indicating that the defect was not in a plasma membrane receptor: Because of the phagocytosis defect, the mutants were unable to grow when cultured in suspensions of heat-killed bacteria. The mutants exhibited normal capacities for fluid phase endocytosis and grew as rapidly as parental (AX4) cells in axenic medium. Both the defects in phagocytosis and growth on bacteria were corrected when the mutant Dictyostelium cells were cultured on solid substrates. Reversion and genetic complementation analysis suggested that the mutant phenotypes were caused by single gene defects. While the precise site of action of the mutations was not established, the mutations are likely to affect an early signaling event because the binding of bacteria to mutant cells in suspension was unable to trigger the localized polymerization of actin filaments required for ingestion; other aspects of actin function appeared normal. This class of conditional phagocytosis mutant should prove to be useful for the expression cloning of the affected gene(s).

Decontamination of beef subprimal cuts intended for blade tenderization or moisture enhancement.

The prevalence of Escherichia coli O157:H7 on beef subprimal cuts intended for mechanical tenderization was evaluated. This evaluation was followed by the assessment of five antimicrobial interventions at minimizing the risk of transferring E. coli O157:H7 to the interior of inoculated subprimal cuts during blade tenderization (BT) or moisture enhancement (ME). Prevalence of E. coli O157:H7 on 1,014 uninoculated beef subprimals collected from six packing facilities was 0.2%. Outside round pieces inoculated with E. coli O157:H7 at 10(4) CFU/100 cm2 were treated with (i) no intervention, (ii) surface trimming, (iii) hot water (82 degrees C), (iv) warm 2.5% lactic acid (55 degrees C), (v) warm 5.0% lactic acid (55 degrees C), or (vi) 2% activated lactoferrin followed by warm 5.0% lactic acid (55 degrees C) and then submitted to BT or ME. Prevalence (n=196) of internalized (BT and ME) E. coli O157:H7 was 99%. Enumeration of E. coli 0157:H7 (n=192) revealed mean surface reductions of 0.93 to 1.10 log CFU/100 cm2 for all antimicrobial interventions. E. coli O157:H7 was detected on 3 of the 76 internal BT samples and 73 of the 76 internal ME samples. Internal ME samples with no intervention had significantly higher mean E. coli O157:H7 populations than did those internal samples treated with an intervention, but there were no significant differences in E. coli O157:H7 populations among internal BT samples. Results of this study demonstrate that the incidence of E. coli O157:H7 on the surface of beef subprimal cuts is low and that interventions applied before mechanical tenderization can effectively reduce the transfer of low concentrations of E. coli O157:H7 to the interior of beef subprimal cuts.

Colchicine blocks the action of parathyroid hormone but not nicotinamide on renal phosphate transport.

Nicotinamide, like parathyroid hormone, is a rapidly acting specific inhibitor of Na+-dependent transport of phosphate (Pi) across the brush-border membrane of the proximal tubule of the mammalian kidney. Pretreatment of rats with colchicine (0.7 mg/kg body weight) for 1 h led to a significantly diminished phosphaturic response to parathyroid hormone (synthetic 1-34 fragment, 4 micrograms/kg). In contrast, the same dose of colchicine had no effect on the renal response to nicotinamide (1.0 g/kg), measured both as the change in urinary Pi excretion and as Na+-dependent Pi uptake by isolated brush-border membrane vesicles. These data suggest indirectly that the intracellular mechanism that mediates the inhibitory effects of nicotinamide on renal Pi transport does not require intact microtubules.

Progress and problems in immunoassays for serum pituitary gonadotrophins: evidence from the UK external quality assessment schemes, (EQAS) 1980-1988.

Trends in the quality of assays for serum gonadotrophins performed by laboratories in the UK EQAS during the 1980s are reviewed, with particular reference to the effects of the recent introduction of immunometric assays (IMA) as an alternative to radioimmunoassay (RIA). IMA gave results which were on average 17% higher than RIA for FSH, and 33% lower for LH. These bias characteristics were not entirely accounted for by differences in assay standardisation, but appeared to reflect the different isoforms of the hormones detected by the monoclonal antibodies used in the IMA. Between-laboratory agreement remained, consequently, unsatisfactory overall (geometric coefficient of variation, GCV, 20-30%), although good within method groups (GCV 10%). IMA were less vulnerable to non-specific background interference than many RIA, and could avoid interference from HCG. Some IMA were, however, vulnerable to interference from heterophilic antibodies in patients' sera. The differences between RIA and the various IMA in numerical values reported, and in their vulnerability to interferences underline the need for care in interpreting assay results.

Quality of performance of assays for serum growth hormone in the United Kingdom (UK): evidence from the UK external quality assessment scheme, 1980-1987.

The performance of laboratories in the UK External Quality Assessment Scheme for growth hormone (GH) during the years 1980 to 1987 is reviewed. The number of participating laboratories has increased steadily and is at present 67; about one half use immunoradiometric assay (IRMA) kits and the use of such kits is increasing at the expense of 'in-house' radioimmunoassays (RIAs). The consensus mean, which is used as the target value for assessing performance, has remained accurate and reproducible against this changing background. The between-laboratory geometric coefficient of variation has remained at about 18% during the period reviewed, revealing unsatisfactory between-laboratory agreement. This is in part due to poor within-laboratory performance in a small proportion of laboratories but it is also due to the negative bias of some IRMA kits. Most IRMA kits do appear, however, to provide marginally better within-laboratory precision than RIA, and are less vulnerable to non-specific interference. The laboratory interpretation of results was assessed from time to time, and was generally satisfactorily performed. In an attempt to identify the causes of poor performance, a detailed survey of assay methods and laboratory practice has been carried out; the results are described in an associated report [1].

A comparison of the lung deposition of budesonide from Easyhaler, Turbuhaler and pMDI plus spacer in asthmatic patients.

Inhaled corticosteroids in pressurized metered does inhalers (pMDIs) are often delivered via a large volume spacer device, but these are bulky and inconvenient. Dry powder inhalers (DPIs) provide a highly portable and convenient propellant-free alternative to pMDIs for asthma maintenance therapy However, each DPI could have unique in vivo delivery characteristcs. In order to quantify the total and regional lung deposition of budesonide (200 microg) from (a) Easyhaler, (b) Turbuhaler and (c) pMDI plus Nebuhaler 750 ml spacer, a three-way randomized cross-over study was carried out in 12 mild to moderate asthmatic patients. Deposition was quantified by the imaging technique of gamma scintigraphy Optimal inhalation techniques were used throughout. Mean (SD) whole lung deposition (% metered dose) was similar for Easyhaler [18.5 (7.8) %] and Turbuhaler [21.8 (8.2) %], but was significantly higher for pMDI plus Nebuhaler [44.1 (10.0) %, P < 0.01]. The regional distribution patterns in the lungs were predominantly central for all three devices. Nebuhaler reduced oropharyngeal deposition significantly compared with the two DPIs. Easyhaler showed comparable deposition to Turbuhaler and hence drugs delivered by Easyhaler would be expected to have a similar clinical effect to those delivered by Turbuhaler in asthma maintenance therapy.

Quality of performance of assays for maternal serum alphafetoprotein in the United Kingdom: evidence from the UK external quality assessment scheme 1980-87.

Between-laboratory agreement in the UK EQAS for maternal serum alphafetoprotein has improved steadily since 1976 and the geometric coefficient of variation is now 8 to 9% at levels of 50 to 150 kU/L. The use of a common standard and commercial assay kits appear to have contributed to this trend. Within-laboratory performance is also generally good, about 50% of participants maintain a bias of less than 5%, together with a scatter of the bias of less than 10%. These data indicate that the quality of assay performance is adequate for the requirements of screening programmes for open neural tube effects. The improvement in laboratory performance is such that between-laboratory agreement is better expressed in kU/L than as multiples of the median. Errors in interpretation of clearly normal or abnormal results appear to be rare (0.4%), and contribute little to overall false positive and negative rates. However, they assume significance as most are due to avoidable errors.

Assays for prolactin: guidelines for the provision of a clinical biochemistry service.

This paper summarises the views of the authors on the provision of a prolactin assay service. We discuss the pathophysiology of prolactin secretion and the clinical indications that arise from that. We cover the rather complex issue of the definition of normal and elevated prolactin levels. From these considerations, certain guidelines on the analytical performance of prolactin assays and their provision in a clinical biochemistry service are given. The extent to which currently available methods and performance as revealed by the UK External Quality Assessment Scheme (EQAS) match these guidelines are described and certain conclusions are reached. Finally, probable future developments are briefly discussed. The main conclusions and recommendations are as follows: Reagents of appropriate quality are available to enable prolactin immunoassays to be provided in UK clinical biochemistry laboratories. These are provided either separately or in the form of kits from both commercial and NHS sources. There is no requirement for individual laboratories to undertake their own antiserum production or prolactin iodination. Acceptable performance (as defined using internal QC procedures and the UK EQAS) is achievable using these reagents/kits, although one commercial kit shows a consistent marked negative bias. Reference ranges, including 'normal ranges', show considerable between-centre variability. Many centres have not established their own ranges, even those using in-house methods. Reference ranges for use in clinical biochemistry laboratories are proposed in this report. Some general guidance on the provision of a prolactin service is given, although this does not differ in principle from that appropriate for other peptide hormone analytes. There is no evidence that centres with small workloads perform any worse than average, although it may be more cost-efficient for such centres to send the samples elsewhere. As with other peptide analytes, non-isotopic immunometric methodology is likely to replace current radioimmunoassay methods in the near future.

Improved performance of plasma gonadotrophin assays using common reagents and assay protocols: evidence from the UK External Quality Assessment Scheme.

Radioimmunoassay kits prepared in the Chelsea Hospital for Women for follicle stimulating hormone (FSH) and luteinising hormone (LH) have been used in 26 UK laboratories for over 2 years. Data from the UK External Quality Assessment Schemes for FSH and LH have been used to provide an independent assessment of the performance of these kits over a 12-month period. For both analytes, users of the kits were found to have: a low variability of the bias, implying good within-laboratory, between-assay precision; a lower between-laboratory, within-sample geometric coefficient of variation than users of 'own' methods, implying better between-laboratory agreement; method bias that did not differ significantly from laboratories using 'own' method protocols. This survey indicates that a non-commercial organisation can produce immunoassay kits that improve the quality of FSH and LH assays generally available.

Progress in immunoassays for serum prolactin: evidence from the UK External Quality Assessment Scheme (EQAS) 1980-1989.

The quality of serum prolactin assays routinely performed by UK laboratories has been monitored in an external quality assessment scheme (EQAS) over a 10-year period, during which participation in the EQAS increased three-fold, and considerable changes in methods and standardization were introduced. The all-laboratory mean was used as the sample target value, and proved to be stable and accurate. Overall between-laboratory agreement in the clinically important range improved from a geometric coefficient of variation (GCV) of 25% to 14%. This appears to reflect the increased use of kits in place of 'in-house' assays, the more widespread availability of international standards and the absence of any marked differences in bias between the commonly used methods. Published guidelines on the clinical interpretation of prolactin values should, therefore, be widely applicable. The EQAS data indicate that, in general, the quality of performance of prolactin assays is adequate for their clinical application.