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The Atmospheric River Tracking Method Intercomparison Project (ARTMIP) is an international collaborative effort to understand and quantify the uncertainties in atmospheric river (AR) science based on detection algorithm alone. Currently, there are many AR identification and tracking algorithms in the literature with a wide range of techniques and conclusions. ARTMIP strives to provide the community with information on different methodologies and provide guidance on the most appropriate algorithm for a given science question or region of interest. All ARTMIP participants will implement their detection algorithms on a specified common dataset for a defined period of time. The project is divided into two phases: Tier 1 will utilize the Modern-Era Retrospective analysis for Research and Applications, version 2 (MERRA-2) reanalysis from January 1980 to June 2017 and will be used as a baseline for all subsequent comparisons. Participation in Tier 1 is required. Tier 2 will be optional and include sensitivity studies designed around specific science questions, such as reanalysis uncertainty and climate change. High-resolution reanalysis and/or model output will be used wherever possible. Proposed metrics include AR frequency, duration, intensity, and precipitation attributable to ARs. Here, we present the ARTMIP experimental design, timeline, project requirements, and a brief description of the variety of methodologies in the current literature. We also present results from our 1-month proof-of-concept trial run designed to illustrate the utility and feasibility of the ARTMIP project.

This study examined whether connecting storytelling and tinkering can advance early STEM (science, technology, engineering, and mathematics) learning opportunities for children. A total of 62 families with 4- to 10-year-old ( M  = 8.03) children were observed via Zoom. They watched a video invitation to tinker at home prepared by museum educators prior to tinkering. Then, half of the families were prompted to think up a story before tinkering (story-based tinkering group), whereas the other half were simply asked to begin tinkering (no-story group). Once they had finished tinkering, researchers elicited children's reflections about their tinkering experience. A subset of the families ( n  = 45) also reminisced about their tinkering experience several weeks later. The story instructions provided before tinkering engendered children's storytelling during tinkering and when reflecting on the experience. Children in the story-based tinkering group also talked the most about STEM both during tinkering, and subsequently when reminiscing with their parents about their tinkering experience., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Marcus, Solis, Sellars and Haden.)

The law relating to consent and the process dentists need to go through to gain valid and informed consent to treat patients changed significantly following the landmark ruling of Montgomery v Lanarkshire Health Board. In this paper, we revisit the history of patient consent, give an update on the current legal situation in the UK, and produce a unique 'consent workflow' to aid in the process of gaining valid and informed consent to treat. The aim is to clarify the legal standing and provide a framework that dentists and other healthcare professionals can adapt to their current clinical practice while increasing the confidence of those involved in the consent process; both professionals and patients., (© 2023. The Author(s), under exclusive licence to the British Dental Association.)

Since its beginnings in the mid-1990s, evidence-based dentistry (EBD) has gradually gained acceptance into the understanding of dental practitioners. Despite this, most treatment provided by dentists cannot truly be described as being based on experimental evidence. The aim of this paper is to explore the reasons why EBD has not yet reached its full potential. The weakness of evidence produced, as well as the attitude of dentists towards EBD, will be examined. The role of the trusted source in disseminating information will be discussed and examples are given of how this concept could be used to further integrate evidence into everyday practice. Suggestions will be made regarding how research waste can be cut by producing less but more relevant research. Furthermore, realistic ideas on how EBD can be utilised in practice will be provided with the aim to shift towards the concept of evidence-based practice (EBP).

It was a watershed moment when Archie Cochrane published his work on Effectiveness and efficiency: random reflections on health services which was considered the start of evidence-based healthcare as we now know it. From there onward, evidence-based dentistry (EBD) has developed and evolved and there has been little attention to the interlink between EBD and ethics. The aim of this paper is to explore some of the ethical basis of evidence-based approach to healthcare utilising Beauchamp and Childress' four principles. EBD will be examined in relation to a variety of ethical theories. The case will be made that dentistry can, at times, be considered the orphaned field of medicine and an examination will be presented about how this may affect the uptake of EBD in practice. While exploring the strengths and weaknesses of EBD from an ethical viewpoint, we will highlight some of the challenges facing many dental practitioners in judging what is considered high-quality evidence and examine ways in which this could be improved with links to patient outcomes from an ethical perspective.

Background: Older women have poorer survival from breast cancer, which may be at least partly due to poor breast cancer awareness leading to delayed presentation and more advanced stage at diagnosis. In a randomised trial, an intervention to promote early presentation of breast cancer in older women increased breast cancer awareness at 1 year compared with usual care (24 versus 4%). We examined its effectiveness in routine clinical practice., Methods: We piloted the intervention delivered by practising health professionals to women aged about 70 in four breast screening services. We measured the effect on breast cancer awareness at 1 year compared with comparison services, where women did not receive the intervention., Results: At 1 year, 25% of women in pilot services were breast cancer aware compared with 4% in comparison services (p = 0.001). The components of breast cancer awareness were knowledge of breast cancer non-lump symptoms (pilot: 63% vs comparison: 82% at 1 year; OR = 2.56, 95% CI 1.92-3.42), knowledge of age related risk (pilot: 8% vs comparison: 36% at 1 year; OR = 5.56, 95% CI 4.0-7.74) and reported breast checking (pilot: 70% vs comparison: 78% at 1 year; OR = 1.49, 95% CI 1.13-1.96)., Conclusion: The intervention may be as effective in routine clinical practice as in a randomised controlled trial. This intervention has the potential to reduce patient delay in the diagnosis of breast cancer in older women., Trial Registration: The PEP trial was registered with the International Standard Registered Clinical/soCial sTudy Number (ISRCTN) as a clinical trial ( ISRCTN31994827 ) on 3rd October 2007.

Background: The value of screen detection and treatment of ductal carcinoma in situ (DCIS) is a matter of controversy. At present, the extent to which the diagnosis and treatment of DCIS could prevent the occurrence of invasive breast cancer in the future is not clear. We sought to estimate the association between detection of DCIS at screening and invasive interval cancers subsequent to the relevant screen., Methods: We obtained aggregate data for screen-detected cancers from 84 local screening units within 11 regional Quality Assurance Reference Centres in England, Wales, and Northern Ireland from the National Health Service Breast Screening Programme. Data for DCIS diagnoses were obtained for women aged 50-64 years who were invited to and attended mammographic breast screening from April 1, 2003, to March 31, 2007 (4 screening years). Patient-level data for interval cancer arising in the 36 months after each of these were analysed by Poisson regression with invasive interval cancer screen detection rate as the outcome variable; DCIS detection frequencies were fitted first as a continuous and then as a categorical variable. We repeated this analysis after adjustment with both small size and high-grade invasive screen-detected cancers., Findings: We analysed data for 5,243,658 women and on interval cancers occurring in the 36 months after the relevant screen. The average frequency of DCIS detected at screening was 1·60 per 1000 women screened (median 1·50 [unit range 0·54-3·56] [corrected to] per 1000 women). There was a significant negative association of screen-detected DCIS cases with the rate of invasive interval cancers (Poisson regression coefficient -0·084 [95% CI -0·13 to -0·03]; p=0·002). 90% of units had a DCIS detection frequency within the range of 1·00 to 2·22 per 1000 women; in these units, for every three screen-detected cases of DCIS, there was one fewer invasive interval cancer in the next 3 years. This association remained after adjustment for numbers of small screen-detected invasive cancers and for numbers of grade 3 invasive screen-detected cancers., Interpretation: The association between screen-detected DCIS and subsequent invasive interval cancers suggests that detection and treatment of DCIS is worthwhile in prevention of future invasive disease., Funding: UK Department of Health Policy Research Programme and NHS Cancer Screening Programmes., (Copyright © 2016 Duffy et al. Open Access article distributed under the terms of CC BY. Published by Elsevier Ltd.. All rights reserved.)

Background: The introduction of two-view mammography at incident (subsequent) screens in the National Health Service Breast Screening Programme (NHSBSP) has led to an increased number of cancers detected at screen. However, the effect of two-view mammography on interval cancer rates has yet to be assessed., Methods: Routine screening and interval cancer data were collated from all screening programmes in the United Kingdom for women aged 50-64, screened between 1 April 2003 and 31 March 2005. Interval cancer rates were compared based on whether two-view mammography was in use at the last routine screen., Results: The reduction in interval cancers following screening using two-view mammography compared with one view was 0.68 per 1,000 women screened. Overall, this suggests the introduction of two-view mammography at incident screen was accompanied by a 15-20% reduction in interval cancer rates in the NHSBSP., Conclusion: The introduction of two-view mammography at incident screens is associated with a reduction in incidence of interval cancers. This is consistent with previous publications on a contemporaneous increase in screen-detected cancers. The results provide further evidence of the benefit of the use of two-view mammography at incident screens.

Background: X-ray mammography remains the predominant test for screening for breast cancer, with the aim of reducing breast cancer mortality. In the English NHS Breast Screening Programme each woman's mammograms are examined separately by two expert readers. The two readers read each batch in the same order and each indicates if there should be recall for further tests. This is a highly skilled, pressurised, repetitive and frequently intellectually unchallenging activity where readers examine one or more batches of 30-50 women's mammograms in each session. A vigilance decrement or performance decrease over time has been observed in similar repetitive visual tasks such as radar operation., Methods/design: The CO-OPS study is a pragmatic, multi-centre, two-arm, double blind cluster randomised controlled trial of a computer software intervention designed to reduce the effects of a vigilance decrement in breast cancer screening. The unit of randomisation is the batch. Intervention batches will be examined in the opposite order by the two readers (one forwards, one backwards). Control batches will be read in the same order as one another, as is current standard practice. The hypothesis is that cancer detection rates will be higher in the intervention group because each readers' peak performance will occur when examining different women's mammograms. The trial will take place in 44 English breast screening centres for 1 year and 4 months. The primary outcome is cancer detection rate, which will be extracted from computer records after 1 year of the trial. The secondary outcomes include rate of disagreement between readers (a more statistically powerful surrogate for cancer detection rate), recall rate, positive predictive value, and interval cancer rate (cancers found between screening rounds which will be measured three years after the end of the trial)., Discussion: This is the first trial of an intervention to ameliorate a vigilance decrement in breast cancer screening., Trial Registration: ISRCTN46603370 (submitted: 24 October 2012, date of registration: 26 March 2013).

Background. Women over 70 with breast cancer have poorer one-year survival and present at a more advanced stage than younger women. Promoting early symptomatic presentation in older women may reduce stage cost effectively and is unlikely to lead to overdiagnosis. After examining efficacy in a randomised controlled trial, we piloted a brief health professional-delivered intervention to equip women to present promptly with breast symptoms, as an integral part of the final invited mammogram at age ~70, in the English National Health Service Breast Screening Programme. Methods. We trained mammographers, who then offered the intervention to older women in four breast screening services. We examined breast cancer awareness at baseline and one month in women receiving the intervention, and also in a service where the intervention was not offered. Results. We trained 27 mammographers to deliver the intervention confidently to a high standard. Breast cancer awareness increased 7-fold at one month in women receiving the intervention compared with 2-fold in the comparison service (odds ratio 15.2, 95% confidence interval 10.0 to 23.2). Conclusions. The PEP Intervention can be implemented in routine clinical practice with a potency similar to that achieved in a randomised controlled trial. It has the potential to reduce delay in diagnosis for breast cancer in older women.

Codling moth, Cydia pomonella (L.), is a cosmopolitan pest of apple, potentially causing severe damage to the fruit. Currently used methods of combating this insect do not warrant full success or are harmful to the environment. The use of plant-derived semiochemicals for manipulation with fruit-infesting behavior is one of the new avenues for controlling this pest. Here, we explore the potential of Ginkgo biloba and its synthetic metabolites for preventing apple feeding and infestation by neonate larvae of C. pomonella. Experiments with crude extracts indicated that deterrent constituents of ginkgo are present among alkylphenols, terpene trilactones, and flavonol glycosides. Further experiments with ginkgo synthetic metabolites of medical importance, ginkgolic acids, kaempferol, quercetin, isorhamnetin, ginkgolides, and bilobalide, indicated that three out of these chemicals have feeding deterrent properties. Ginkgolic acid 15:0 prevented fruit infestation at concentrations as low as 1 mg/mL, bilobalide had deterrent effects at 0.1 mg/mL and higher concentrations, and ginkgolide B at 10 mg/mL. On the other hand, kaempferol and quercetin promoted fruit infestation by codling moth neonates. Ginkgolic acids 13:0, 15:1, and 17:1, isorhamnetin, and ginkgolides A and C had no effects on fruit infestation-related behavior. Our research is the first report showing that ginkgo constituents influence fruit infestation behavior and have potential applications in fruit protection.

Despite their importance as members of the Roundabout (Robo) family in the control of axonal and vascular patterning, the transcriptional regulation of these genes is poorly understood. In this study, we show that members of the Sry-related high mobility box (Sox) transcription factor family as being transcriptional regulators of roundabout4 (robo4), a Robo gene family member that participates in sprouting angiogenesis in vivo, in zebrafish. Double whole mount in situ hybridization analysis in zebrafish embryos revealed co-localization of the vascular relevant Sox factors sox7 or sox18 mRNA with robo4 transcripts in developing intersomitic vessels. A 3-kb human ROBO4 promoter element was able to drive reporter expression in zebrafish to recapitulate the endogenous temporal intersomitic vessel expression pattern of robo4. EMSA analysis confirmed binding of Sox18 to a canonical Sox binding site (from -1170 bp to -1176 bp) in the ROBO4 promoter (3 kb), and mutation analysis indicated that this site was partially responsible for ROBO4 promoter activity in ECs. A combination of gain- and loss-of-function analysis identified Sox7 and Sox18 co-regulation of robo4 but not fli1a transcripts in zebrafish. Finally, Sox-mediated robo4 transcriptional regulation is conserved across evolution. These studies imply Sox-mediated transcriptional regulation of Robo4 in the developing embryonic vasculature.

Context: Extracts of Artemisia annua (L.) (Asteraceae) and artemisinins are used for treatment of malaria, parasitic infections and have potent anticancer properties in cell lines. Eucalyptus oil and 1,8-cineole have antimicrobial, immune-stimulatory, anti-inflammatory, antioxidant, analgesic, and spasmolytic effects. Codling moth, Cydia pomonella, (L.) (Tortricidae), is a major cosmopolitan pest of the apple, potentially causing damage translating to 40 billion US dollars per year, globally. Currently used control measures are either hazardous to agricultural workers and harmful to environment, or ineffective. The potential of plant-derived semiochemicals for codling moth control is heavily understudied., Objective: This study evaluated the potential of A. annua extracts, and two chemicals that this plant contains, artemisinin and 1,8-cineole, for preventing apple feeding and infestation by neonate Cydia pomonella larvae., Methods: We studied effects of A. annua extracts, artemisinin and 1,8-cineole on apple infestation by neonate codling moth larvae using fruit choice assay in laboratory experiments. Preference of fruit treated with test solutions versus fruit treated with solvent was recorded and analyzed., Results: Crude A. annua extracts prevented fruit feeding at 1, 3, and 10 mg/ml. Artemisinin had feeding deterrent effects at 10 and 30 mg/ml, and 1,8-cineole at 100 and 300 mg/ml., Discussion and Conclusions: A. annua contains chemicals that prevent apple infestation by codling moth neonates. Artemisinin and 1,8-cineole are among them, but there are other, polar constituents of A. annua, which have similar effects. There is a potential of using our findings in codling moth control and production of codling moth-resistant apples.

Objective: To assess the feasibility and acceptability of randomizing the phased introduction of the extension of the invited age range in the National Health Service (NHS) Breast Screening Programme in England from 50-70 to 47-73 years., Setting: Six volunteer breast screening units (BSUs) in England., Methods: Cluster-randomized trial of invitation versus no invitation for breast screening., Study Participants: women aged 47-49 and 71-73 years in screening batches randomized between 1 June 2009 and 31 May 2010., Outcomes: workload, screening uptake among women invited, self-referrals among women not invited, and screening outcomes among women invited., Results: A total of 312 screening batches (clusters) were randomized including 60,708 women. Screening uptake was 63% in women aged 47-49 and 62% in women aged 71-73. Those who attended screening in the younger age group were more likely to be recalled for assessment than older attendees (7.5% vs. 3.0%) but less likely to be diagnosed with breast cancer (0.5% vs. 1.1%). Among women not invited, 0.2% of those aged 47-49 and 6.8% of those aged 71-73 self-referred for screening. Despite the extra workload BSUs largely coped although there was some slippage in round lengths and other targets., Conclusion: No major problems of feasibility or acceptability of randomization were found. This pilot study has informed the randomized phasing-in of the age extension across the whole of England.

Craniometaphyseal dysplasia (CMD) is a rare skeletal disorder characterized by progressive thickening and increased mineral density of craniofacial bones and abnormally developed metaphyses in long bones. Linkage studies mapped the locus for the autosomal dominant form of CMD to an approximately 5-cM interval on chromosome 5p, which is defined by recombinations between loci D5S810 and D5S1954. Mutational analysis of positional candidate genes was performed, and we describe herein three different mutations, in five different families and in isolated cases, in ANK, a multipass transmembrane protein involved in the transport of intracellular pyrophosphate into extracellular matrix. The mutations are two in-frame deletions and one in-frame insertion caused by a splicing defect. All mutations cluster within seven amino acids in one of the six possible cytosolic domains of ANK. These results suggest that the mutated protein has a dominant negative effect on the function of ANK, since reduced levels of pyrophosphate in bone matrix are known to increase mineralization.

The vestibular and ototoxic effects of the aminoglycoside antibiotics (streptomycin, gentamycin, kanamycin, tobramycin, neomycin) are well known; streptomycin, in particular, has been found to cause irreversible, profound, high frequency sensorineural deafness in hypersensitive persons. Aminoglycoside ototoxicity occurs both sporadically and within families and has been associated with a mitochondrial DNA (mtDNA) 1555A to G point mutation in the 12S ribosomal RNA gene. We report on the molecular analysis of a South African family with streptomycin induced sensorineural deafness in which we have found transmission of this same predisposing mutation. It is now possible to identify people who are at risk of hearing loss if treated with aminoglycosides in the future and to counsel them accordingly. In view of the fact that aminoglycoside antibiotics remain in widespread use for the treatment of infections, in particular for tuberculosis, which is currently of epidemic proportions in South Africa, this finding has important implications for the family concerned. In addition, other South African families may potentially be at risk if they carry the same mutation.

An autosomal recessive syndrome of progressive rod-cone dystrophy, sensorineural deafness, and renal dysfunction was identified in 14 children in 9 Afrikaner families in South Africa. The renal involvement, which is of the Fanconi type, leads to rickets-like skeletal changes and kidney failure. Each of the children was initially misdiagnosed as having retinitis pigmentosa or Usher syndrome, on a basis of minor retinal pigmentation. This condition, which appears to be a hitherto undocumented entity, warrants differentiation from these disorders.