Persistent unexplained congenital clitoromegaly in females born extremely prematurely

Objective: Unexplained clitoromegaly is a rare but well recognised feature in girls born premature. Although detected at birth, girls may re-present during childhood to paediatric urologists and gynaecologists who should be aware of this condition. The aim of the study was to describe the clinical findings and management of a series of girls presenting with persistent congenital clitoromegaly associated with prematurity. / Materials and methods: This was a retrospective notes review set in a tertiary referral centre for Paediatric and Adolescent Gynaecology (PAG). / Results: Eight girls with a mean age of 6 years were seen over an eight year period. In all cases a Disorder of Sex Development (DSD) had been previously excluded. The main symptoms were discomfort or concern about appearance. On examination five girls had excess skin over the clitoris and three had enlarged corporal tissue. Management included reassurance and simple measures to ease discomfort. In two cases the parents requested referral to a paediatric urologist to consider clitoral surgery. / Conclusion: As survival rates for extreme prematurity improve, paediatric urologists and gynaecologists are likely to see more of these cases. Clinicians must be familiar with this condition to ensure children are managed appropriately

Nomadic ecology shaped the highland geography of Asia's Silk Roads

There are many unanswered questions about the evolution of the ancient 'Silk Roads' across Asia. This is especially the case in their mountainous stretches, where harsh terrain is seen as an impediment to travel. Considering the ecology and mobility of inner Asian mountain pastoralists, we use ‘flow accumulation’ modelling to calculate the annual routes of nomadic societies (from 750 m to 4,000 m elevation). Aggregating 500 iterations of the model reveals a high-resolution flow network that simulates how centuries of seasonal nomadic herding could shape discrete routes of connectivity across the mountains of Asia. We then compare the locations of known high-elevation Silk Road sites with the geography of these optimized herding flows, and find a significant correspondence in mountainous regions. Thus, we argue that highland Silk Road networks (from 750 m to 4,000 m) emerged slowly in relation to long-established mobility patterns of nomadic herders in the mountains of inner Asia

Improved Roundtrip Spanners, Emulators, and Directed Girth Approximation

Roundtrip spanners are the analog of spanners in directed graphs, where the roundtrip metric is used as a notion of distance. Recent works have shown existential results of roundtrip spanners nearly matching the undirected case, but the time complexity for constructing roundtrip spanners is still widely open. This paper focuses on developing fast algorithms for roundtrip spanners and related problems. For any $n$-vertex directed graph $G$ with $m$ edges (with non-negative edge weights), our results are as follows: - 3-roundtrip spanner faster than APSP: We give an $\tilde{O}(m\sqrt{n})$-time algorithm that constructs a roundtrip spanner of stretch $3$ and optimal size $O(n^{3/2})$. Previous constructions of roundtrip spanners of the same size either required $\Omega(nm)$ time [Roditty, Thorup, Zwick SODA'02; Cen, Duan, Gu ICALP'20], or had worse stretch $4$ [Chechik and Lifshitz SODA'21]. - Optimal roundtrip emulator in dense graphs: For integer $k\ge 3$, we give an $O(kn^2\log n)$-time algorithm that constructs a roundtrip \emph{emulator} of stretch $(2k-1)$ and size $O(kn^{1+1/k})$, which is optimal for constant $k$ under Erd\H{o}s' girth conjecture. Previous work of [Thorup and Zwick STOC'01] implied a roundtrip emulator of the same size and stretch, but it required $\Omega(nm)$ construction time. Our improved running time is near-optimal for dense graphs. - Faster girth approximation in sparse graphs: We give an $\tilde{O}(mn^{1/3})$-time algorithm that $4$-approximates the girth of a directed graph. This can be compared with the previous $2$-approximation algorithm in $\tilde{O}(n^2, m\sqrt{n})$ time by [Chechik and Lifshitz SODA'21]. In sparse graphs, our algorithm achieves better running time at the cost of a larger approximation ratio.Comment: To appear in SODA 202

Approximation Algorithms and Hardness for nn-Pairs Shortest Paths and All-Nodes Shortest Cycles

We study the approximability of two related problems on graphs with $n$ nodes and $m$ edges: $n$-Pairs Shortest Paths ($n$-PSP), where the goal is to find a shortest path between $O(n)$ prespecified pairs, and All Node Shortest Cycles (ANSC), where the goal is to find the shortest cycle passing through each node. Approximate $n$-PSP has been previously studied, mostly in the context of distance oracles. We ask the question of whether approximate $n$-PSP can be solved faster than by using distance oracles or All Pair Shortest Paths (APSP). ANSC has also been studied previously, but only in terms of exact algorithms, rather than approximation. We provide a thorough study of the approximability of $n$-PSP and ANSC, providing a wide array of algorithms and conditional lower bounds that trade off between running time and approximation ratio. A highlight of our conditional lower bounds results is that for any integer $k\ge 1$, under the combinatorial $4k$-clique hypothesis, there is no combinatorial algorithm for unweighted undirected $n$-PSP with approximation ratio better than $1+1/k$ that runs in $O(m^{2-2/(k+1)}n^{1/(k+1)-\epsilon})$ time. This nearly matches an upper bound implied by the result of Agarwal (2014). A highlight of our algorithmic results is that one can solve both $n$-PSP and ANSC in $\tilde O(m+ n^{3/2+\epsilon})$ time with approximation factor $2+\epsilon$ (and additive error that is function of $\epsilon$), for any constant $\epsilon>0$. For $n$-PSP, our conditional lower bounds imply that this approximation ratio is nearly optimal for any subquadratic-time combinatorial algorithm. We further extend these algorithms for $n$-PSP and ANSC to obtain a time/accuracy trade-off that includes near-linear time algorithms.Comment: Abstract truncated to meet arXiv requirement. To appear in FOCS 202

Acoustic Wave Velocity as a Selection Trait in Eucalyptus nitens

Previous studies in Eucalyptus nitens have revealed favourable genetic correlations exist between acoustic wave velocity (AWV) in standing trees and modulus of elasticity (MOE), which can determine the suitability of trees for structural timber and/or engineered wood products. This study investigates the strength and stability of genetic variation in standing tree AWV across a range of environments in Tasmania, where there are a number of large plantation estates and breeding trials. Trees under study were from open-pollinated progeny trials established in 1993. Across sites, for standing tree AWV the ranking of E. nitens races did not change and within-race additive genetic correlations were strong (0.61 to 0.99). Heritabilities (0.16 to 0.74) and coefficients of additive genetic variation (2.6 to 4.8) were moderate for this trait. Correlations between standing tree AWV and both basic density and diameter at breast height (DBH) were favourable. Results indicate that there is potential to improve MOE in E. nitens through the exploitation of genetic variation in AWV among and within races, the expression of genetic variation in AWV is relatively stable across different growing environments, and past selection for basic density and growth in pulpwood breeding programs is unlikely to have adversely affected MOE

Do PTK2 gene polymorphisms contribute to the interindividual variability in muscle strength and the response to resistance training? A preliminary report.

The protein tyrosine kinase-2 (PTK2) gene encodes focal adhesion kinase, a structural protein involved in lateral transmission of muscle fiber force. We investigated whether single-nucleotide polymorphisms (SNPs) of the PTK2 gene were associated with various indexes of human skeletal muscle strength and the interindividual variability in the strength responses to resistance training. We determined unilateral knee extension single repetition maximum (1-RM), maximum isometric voluntary contraction (MVC) knee joint torque, and quadriceps femoris muscle specific force (maximum force per unit physiological cross-sectional area) before and after 9 wk of knee extension resistance training in 51 untrained young men. All participants were genotyped for the PTK2 intronic rs7843014 A/C and 3'-untranslated region (UTR) rs7460 A/T SNPs. There were no genotype associations with baseline measures or posttraining changes in 1-RM or MVC. Although the training-induced increase in specific force was similar for all PTK2 genotypes, baseline specific force was higher in PTK2 rs7843014 AA and rs7460 TT homozygotes than in the respective rs7843014 C- (P = 0.016) and rs7460 A-allele (P = 0.009) carriers. These associations between muscle specific force and PTK2 SNPs suggest that interindividual differences exist in the way force is transmitted from the muscle fibers to the tendon. Therefore, our results demonstrate for the first time the impact of genetic variation on the intrinsic strength of human skeletal muscle

The UK quality and outcomes framework pay-for-performance scheme and spirometry: rewarding quality or just quantity? A cross-sectional study in Rotherham, UK

Background: Accurate spirometry is important in the management of COPD. The UK Quality and Outcomes Framework pay-for-performance scheme for general practitioners includes spirometry related indicators within its COPD domain. It is not known whether high achievement against QOF spirometry indicators is associated with spirometry to BTS standards. Methods: Data were obtained from the records of 3,217 patients randomly sampled from 5,649 patients with COPD in 38 general practices in Rotherham, UK. Severity of airflow obstruction was categorised by FEV1 (% predicted) according to NICE guidelines. This was compared with clinician recorded COPD severity. The proportion of patients whose spirometry met BTS standards was calculated in each practice using a random sub-sample of 761 patients. The Spearman rank correlation between practice level QOF spirometry achievement and performance against BTS spirometry standards was calculated. Results: Spirometry as assessed by clinical records was to BTS standards in 31% of cases (range at practice level 0% to 74%). The categorisation of airflow obstruction according to the most recent spirometry results did not agree well with the clinical categorisation of COPD recorded in the notes (Cohen's kappa = 0.34, 0.30 - 0.38). 12% of patients on COPD registers had FEV1 (% predicted) results recorded that did not support the diagnosis of COPD. There was no association between quality, as measured by adherence to BTS spirometry standards, and either QOF COPD9 achievement (Spearman's rho = -0.11), or QOF COPD10 achievement (rho = 0.01). Conclusion: The UK Quality and Outcomes Framework currently assesses the quantity, but not the quality of spirometry

Regulation of C3 Activation by the Alternative Complement Pathway in the Mouse Retina

The purpose of this study was to examine the retinas of mice carrying hemizygous and null double deletions of Cfb-/- and Cfh-/-, and to compare these with the single knockouts of Cfb, Cfh and Cfd. Retinas were isolated from wild type (WT), Cfb-/-/Cfh-/-, Cfb-/-/Cfh+/-, Cfh-/-/Cfb+/-, Cfb-/-, Cfh-/- Cfd-/-, and Cfd+/- mice. Complement proteins were evaluated by western blotting, ELISA and immunocytochemistry, and retinal morphology was assessed using toluidine blue stained semi-thin sections. WT mice showed staining for C3 and its breakdown products in the retinal vasculature and the basal surface of the retinal pigment epithelium (RPE). Cfb-/- mice exhibited a similar C3 staining pattern to WT in the retinal vessels but a decrease in C3 and its breakdown products at the basal surface of the RPE. Deletion of both Cfb and Cfh restored C3 to levels similar to those observed in WT mice, however this reversal of phenotype was not observed in Cfh-/-/Cfb+/- or Cfb-/-/Cfh+/- mice. Loss of CFD caused an increase in C3 and a decrease in C3 breakdown products along the basal surface of the RPE. Overall the retinal morphology and retinal vasculature did not appear different across the various genotypes. We observed that C3 accumulates at the basal RPE in Cfb-/-, Cfb-/-/Cfh-/-, Cfb-/-/Cfh+/-, Cfd-/- and WT mice, but is absent in Cfh-/- and Cfh-/-/Cfb+/- mice, consistent with its consumption in the serum of mice lacking CFH when CFB is present. C3 breakdown products along the surface of the RPE were either decreased or absent when CFB, CFH or CFD was deleted or partially deleted