The falling chain of Hopkins, Tait, Steele and Cayley

A uniform, flexible and frictionless chain falling link by link from a heap by the edge of a table falls with an acceleration $g/3$ if the motion is nonconservative, but $g/2$ if the motion is conservative, $g$ being the acceleration due to gravity. Unable to construct such a falling chain, we use instead higher-dimensional versions of it. A home camcorder is used to measure the fall of a three-dimensional version called an $xyz$-slider. After frictional effects are corrected for, its vertical falling acceleration is found to be $a_x/g = 0.328 \pm 0.004$. This result agrees with the theoretical value of $a_x/g = 1/3$ for an ideal energy-conserving $xyz$-slider.Comment: 17 pages, 5 figure

Author Correction:C16orf72/HAPSTR1/TAPR1 functions with BRCA1/Senataxin to modulate replication-associated R-loops and confer resistance to PARP disruption

Correction to: Nature Communications https://doi.org/10.1038/s41467-023-40779-9, published online 17 August 2023

Health care costs for the treatment of breast cancer recurrent events: estimates from a UK-based patient-level analysis

Cost pressures and the need to demonstrate cost-effectiveness of new interventions require consideration of the costs of treating disease. This study presents analyses of resource use data covering 199 postmenopausal women who experienced a breast cancer recurrent event between 1991 and 2004 and were treated at the Western General Hospital, Edinburgh. Aggregate (5-year) treatment costs for alternative recurrent events were estimated, as well as the annual costs incurred by patients experiencing contralateral, locoregional, or distant recurrence, who remained alive without further recurrence for a year. The 95% confidence intervals for the 5-year costs of recurrence ranged from £10 000 to £37 000 for locoregional recurrence, and £14 500–£20 000 for distant recurrence. No evidence of significant variations in these costs across time periods between 1991 and 2004 was identified. Annual costs for patients remaining in the same health state showed high initial costs for contralateral and locoregional recurrence, with low costs in subsequent years, while costs associated with distant recurrence declined at a slower rate and plateaued at 4–5 years post-diagnosis. The cost estimates presented in this paper not only inform the magnitude of the resource consequences of breast cancer recurrences, but they are also better suited to informing cost-effectiveness analyses, which have a far greater role in allocating health-care resources

Using system dynamics for collaborative design: a case study

<p>Abstract</p> <p>Background</p> <p>In order to facilitate the collaborative design, system dynamics (SD) with a group modelling approach was used in the early stages of planning a new stroke unit. During six workshops a SD model was created in a multiprofessional group.</p> <p>Aim</p> <p>To explore to which extent and how the use of system dynamics contributed to the collaborative design process.</p> <p>Method</p> <p>A case study was conducted using several data sources.</p> <p>Results</p> <p>SD supported a collaborative design, by facilitating an explicit description of stroke care process, a dialogue and a joint understanding. The construction of the model obliged the group to conceptualise the stroke care and experimentation with the model gave the opportunity to reflect on care.</p> <p>Conclusion</p> <p>SD facilitated the collaborative design process and should be integrated in the early stages of the design process as a quality improvement tool.</p

Distinctive mitochondrial genome of Calanoid copepod Calanus sinicus with multiple large non-coding regions and reshuffled gene order: Useful molecular markers for phylogenetic and population studies

<p>Abstract</p> <p>Background</p> <p>Copepods are highly diverse and abundant, resulting in extensive ecological radiation in marine ecosystems. <it>Calanus sinicus </it>dominates continental shelf waters in the northwest Pacific Ocean and plays an important role in the local ecosystem by linking primary production to higher trophic levels. A lack of effective molecular markers has hindered phylogenetic and population genetic studies concerning copepods. As they are genome-level informative, mitochondrial DNA sequences can be used as markers for population genetic studies and phylogenetic studies.</p> <p>Results</p> <p>The mitochondrial genome of <it>C. sinicus </it>is distinct from other arthropods owing to the concurrence of multiple non-coding regions and a reshuffled gene arrangement. Further particularities in the mitogenome of <it>C. sinicus </it>include low A + T-content, symmetrical nucleotide composition between strands, abbreviated stop codons for several PCGs and extended lengths of the genes <it>atp6 </it>and <it>atp8 </it>relative to other copepods. The monophyletic Copepoda should be placed within the Vericrustacea. The close affinity between Cyclopoida and Poecilostomatoida suggests reassigning the latter as subordinate to the former. Monophyly of Maxillopoda is rejected. Within the alignment of 11 <it>C. sinicus </it>mitogenomes, there are 397 variable sites harbouring three 'hotspot' variable sites and three microsatellite loci.</p> <p>Conclusion</p> <p>The occurrence of the <it>circular subgenomic fragment </it>during laboratory assays suggests that special caution should be taken when sequencing mitogenomes using long PCR. Such a phenomenon may provide additional evidence of mitochondrial DNA recombination, which appears to have been a prerequisite for shaping the present mitochondrial profile of <it>C. sinicus </it>during its evolution. The lack of synapomorphic gene arrangements among copepods has cast doubt on the utility of gene order as a useful molecular marker for deep phylogenetic analysis. However, mitochondrial genomic sequences have been valuable markers for resolving phylogenetic issues concerning copepods. The variable site maps of <it>C. sinicus </it>mitogenomes provide a solid foundation for population genetic studies.</p

The mitochondrial genome of Sinentomon erythranum (Arthropoda: Hexapoda: Protura): an example of highly divergent evolution

<p>Abstract</p> <p>Background</p> <p>The phylogenetic position of the Protura, traditionally considered the most basal hexapod group, is disputed because it has many unique morphological characters compared with other hexapods. Although mitochondrial genome information has been used extensively in phylogenetic studies, such information is not available for the Protura. This has impeded phylogenetic studies on this taxon, as well as the evolution of the arthropod mitochondrial genome.</p> <p>Results</p> <p>In this study, the mitochondrial genome of <it>Sinentomon erythranum </it>was sequenced, as the first proturan species to be reported. The genome contains a number of special features that differ from those of other hexapods and arthropods. As a very small arthropod mitochondrial genome, its 14,491 nucleotides encode 37 typical mitochondrial genes. Compared with other metazoan mtDNA, it has the most biased nucleotide composition with T = 52.4%, an extreme and reversed AT-skew of -0.351 and a GC-skew of 0.350. Two tandemly repeated regions occur in the A+T-rich region, and both could form stable stem-loop structures. Eighteen of the 22 tRNAs are greatly reduced in size with truncated secondary structures. The gene order is novel among available arthropod mitochondrial genomes. Rearrangements have involved in not only small tRNA genes, but also PCGs (protein-coding genes) and ribosome RNA genes. A large block of genes has experienced inversion and another nearby block has been reshuffled, which can be explained by the tandem duplication and random loss model. The most remarkable finding is that <it>trnL2(UUR) </it>is not located between <it>cox1 </it>and <it>cox2 </it>as observed in most hexapod and crustacean groups, but is between <it>rrnL </it>and <it>nad1 </it>as in the ancestral arthropod ground pattern. The "<it>cox1</it>-<it>cox2</it>" pattern was further confirmed in three more representative proturan species. The phylogenetic analyses based on the amino acid sequences of 13 mitochondrial PCGs suggest <it>S</it>. <it>erythranum </it>failed to group with other hexapod groups.</p> <p>Conclusions</p> <p>The mitochondrial genome of <it>S. erythranum </it>shows many different features from other hexapod and arthropod mitochondrial genomes. It underwent highly divergent evolution. The "<it>cox1</it>-<it>cox2</it>" pattern probably represents the ancestral state for all proturan mitogenomes, and suggests a long evolutionary history for the Protura.</p

Anastrozole versus tamoxifen for the prevention of locoregional and contralateral breast cancer in postmenopausal women with locally excised ductal carcinoma in situ (IBIS-II DCIS): a double-blind, randomised controlled trial

Background Third-generation aromatase inhibitors are more effective than tamoxifen for preventing recurrence in postmenopausal women with hormone-receptor-positive invasive breast cancer. However, it is not known whether anastrozole is more effective than tamoxifen for women with hormone-receptor-positive ductal carcinoma in situ (DCIS). Here, we compare the efficacy of anastrozole with that of tamoxifen in postmenopausal women with hormone-receptor-positive DCIS. Methods In a double-blind, multicentre, randomised placebo-controlled trial, we recruited women who had been diagnosed with locally excised, hormone-receptor-positive DCIS. Eligible women were randomly assigned in a 1:1 ratio by central computer allocation to receive 1 mg oral anastrozole or 20 mg oral tamoxifen every day for 5 years. Randomisation was stratified by major centre or hub and was done in blocks (six, eight, or ten). All trial personnel, participants, and clinicians were masked to treatment allocation and only the trial statistician had access to treatment allocation. The primary endpoint was all recurrence, including recurrent DCIS and new contralateral tumours. All analyses were done on a modified intention-to-treat basis (in all women who were randomised and did not revoke consent for their data to be included) and proportional hazard models were used to compute hazard ratios and corresponding confidence intervals. This trial is registered at the ISRCTN registry, number ISRCTN37546358. Results Between March 3, 2003, and Feb 8, 2012, we enrolled 2980 postmenopausal women from 236 centres in 14 countries and randomly assigned them to receive anastrozole (1449 analysed) or tamoxifen (1489 analysed). Median follow-up was 7·2 years (IQR 5·6–8·9), and 144 breast cancer recurrences were recorded. We noted no statistically significant difference in overall recurrence (67 recurrences for anastrozole vs 77 for tamoxifen; HR 0·89 [95% CI 0·64–1·23]). The non-inferiority of anastrozole was established (upper 95% CI <1·25), but its superiority to tamoxifen was not (p=0·49). A total of 69 deaths were recorded (33 for anastrozole vs 36 for tamoxifen; HR 0·93 [95% CI 0·58–1·50], p=0·78), and no specific cause was more common in one group than the other. The number of women reporting any adverse event was similar between anastrozole (1323 women, 91%) and tamoxifen (1379 women, 93%); the side-effect profiles of the two drugs differed, with more fractures, musculoskeletal events, hypercholesterolaemia, and strokes with anastrozole and more muscle spasm, gynaecological cancers and symptoms, vasomotor symptoms, and deep vein thromboses with tamoxifen. Conclusions No clear efficacy differences were seen between the two treatments. Anastrozole offers another treatment option for postmenopausal women with hormone-receptor-positive DCIS, which may be be more appropriate for some women with contraindications for tamoxifen. Longer follow-up will be necessary to fully evaluate treatment differences

The Mitochondrial Genome of Toxocara canis

Toxocara canis (Ascaridida: Nematoda), which parasitizes (at the adult stage) the small intestine of canids, can be transmitted to a range of other mammals, including humans, and can cause the disease toxocariasis. Despite its significance as a pathogen, the genetics, epidemiology and biology of this parasite remain poorly understood. In addition, the zoonotic potential of related species of Toxocara, such as T. cati and T. malaysiensis, is not well known. Mitochondrial DNA is known to provide genetic markers for investigations in these areas, but complete mitochondrial genomic data have been lacking for T. canis and its congeners. In the present study, the mitochondrial genome of T. canis was amplified by long-range polymerase chain reaction (long PCR) and sequenced using a primer-walking strategy. This circular mitochondrial genome was 14162 bp and contained 12 protein-coding, 22 transfer RNA, and 2 ribosomal RNA genes consistent for secernentean nematodes, including Ascaris suum and Anisakis simplex (Ascaridida). The mitochondrial genome of T. canis provides genetic markers for studies into the systematics, population genetics and epidemiology of this zoonotic parasite and its congeners. Such markers can now be used in prospecting for cryptic species and for exploring host specificity and zoonotic potential, thus underpinning the prevention and control of toxocariasis in humans and other hosts