Overview of the Langley subsonic research effort on SCR configuration

Recent advances achieved in the subsonic aerodynamics of low aspect ratio, highly swept wing designs are summarized. The most significant of these advances was the development of leading edge deflection concepts which effectively reduce leading edge flow separation. The improved flow attachment results in substantial improvements in low speed performance, significant delay of longitudinal pitch up, increased trailing edge flap effectiveness, and increased lateral control capability. Various additional theoretical and/or experimental studies are considered which, in conjunction with the leading edge deflection studies, form the basis for future subsonic research effort

A Proposed Grading System to Standardize the Description of Renal Papillary Appearance at the Time of Endoscopy in Patients with Nephrolithiasis

BACKGROUND AND PURPOSE: The appearance of the renal papillae in patients with nephrolithiasis can be quite variable and can range from entirely healthy to markedly diseased. The implications of such findings remain unknown. One potential reason is the lack of a standardized system to describe such features. We propose a novel grading scale to describe papillary appearance at the time of renal endoscopy. METHODS: Comprehensive endoscopic renal assessment and mapping were performed on more than 300 patients with nephrolithiasis. Recurring abnormal papillary characteristics were identified and quantified based on degree of severity. RESULTS: Four unique papillary features were chosen for inclusion in the PPLA scoring system- ductal Plugging, Pitting, Loss of contour, and Amount of Randall's plaque. Unique scores are calculated for individual papillae based on reference examples. CONCLUSIONS: The description and study of renal papillary appearance in stone formers have considerable potential as both a clinical and research tool; however, a standardized grading system is necessary before using it for these purpos

Biopsy proven medullary sponge kidney: clinical findings, histopathology, and role of osteogenesis in stone and plaque formation

Medullary sponge kidney (MSK) is associated with recurrent stone formation, but the clinical phenotype is unclear because patients with other disorders may be incorrectly labeled MSK. We studied 12 patients with histologic findings pathognomonic of MSK. All patients had an endoscopically recognizable pattern of papillary malformation, which may be segmental or diffuse. Affected papillae are enlarged and billowy, due to markedly enlarged inner medullary collecting ducts (IMCD), which contain small, mobile ductal stones. Patients had frequent dilation of Bellini ducts, with occasional mineral plugs. Stones may form over white (Randall's) plaque, but most renal pelvic stones are not attached, and have a similar morphology as ductal stones, which are a mixture of calcium oxalate and apatite. Patients had no abnormalities of urinary acidification or acid excretion; the most frequent metabolic abnormality was idiopathic hypercalciuria. Although both Runx2 and Osterix are expressed in papillae of MSK patients, no mineral deposition was seen at the sites of gene expression, arguing against a role of these genes in this process. Similar studies in idiopathic calcium stone formers showed no expression of these genes at sites of Randall's plaque. The most likely mechanism for stone formation in MSK appears to be crystallization due to urinary stasis in dilated IMCD with subsequent passage of ductal stones into the renal pelvis where they may serve as nuclei for stone formation

Papillary Ductal Plugging Is a Mechanism for Early Stone Retention in Brushite Stone Disease

Purpose Mechanisms of early stone retention in the kidney are under studied and poorly understood. To date attachment via Randall plaque is the only widely accepted theory in this regard, which is best described in idiopathic calcium oxalate stone formers. Brushite stone formers are known to have distinct papillary morphology relative to calcium oxalate stone formers. As such we sought to determine whether stone attachment mechanisms in such patients may be similarly unique. Materials and Methods Patients undergoing percutaneous and or ureteroscopic procedures for stone removal consented to endoscopic renal papillary examination and individual stone collection. Each removed stone was processed using micro computerized tomography to assess the 3-dimensional microstructure and the minerals contained, and search for common structural features indicative of novel mechanisms of early growth and attachment to renal tissue. Results A total of 25 intact brushite stones were removed from 8 patients and analyzed. Video confirmed attachment of 13 of the 25 stones with the remainder believed to have been accidently dislodged during the procedure. Microscopic examination by light and computerized tomography failed to show evidence of Randall plaque associated with any stone containing brushite. Conversely each brushite stone demonstrated microstructural evidence of having grown attached to a ductal plug formed of apatite. Conclusions Three-dimensional analysis of small brushite stones suggests overgrowth on ductal apatite plugs as a mechanism of early stone growth and retention. Such findings represent what is to our knowledge the initial supporting evidence for a novel mechanism of stone formation which has previously been hypothesized but never verified

Association Between Randall's Plaque Stone Anchors and Renal Papillary Pits

Introduction: Renal papillary pits are commonly encountered during ureteroscopy. The mechanism by which such pits arise is unclear. One hypothesis is that pits represent sites where stones overgrowing Randall's plaque (RP) were dislodged. We sought to examine this theory by using digital ureteroscopy and stone μCT. Materials and Methods: Patients undergoing endoscopic stone removal had procedures recorded and stones analyzed by using μCT. Stones with evidence of Randall's plaque anchors (RPAs) were identified in a blinded fashion. Surgical videos were reviewed independently by two urologists. Results: Twenty-eight patients had μCT-confirmed stones with RPA. Among them, 93% were recurrent stone formers and 75% had had prior stone procedures. Metabolic abnormalities were present in 87%, with 79% classified as idiopathic calcium oxalate stone formers. A mean of 7.6 stones with RPA were identified per procedure. In each case, papillary pits were visualized before any stone manipulation and in several cases the active dislodgement of an attached stone led to immediate identification of an underlying pit. Such stones routinely demonstrated an RPA on μCT. The average depth of RPA was 302 ± 172 μm, consistent with the corresponding shallow pits visualized on the papillary surface. Conclusions: Stones overgrowing RP are capable of pulling away a piece of papilla when dislodged, resulting in a visible papillary pit. This process manifests as an RPA on the undersurface of the stone and a papillary pit on the corresponding area of attachment. Identification of pits may help identify patients who form stones primarily by the RP mechanism

A Spectroscopic Orbit for Regulus

We present a radial velocity study of the rapidly rotating B-star Regulus that indicates the star is a single-lined spectroscopic binary. The orbital period (40.11 d) and probable semimajor axis (0.35 AU) are large enough that the system is not interacting at present. However, the mass function suggests that the secondary has a low mass (M_2 > 0.30 M_sun), and we argue that the companion may be a white dwarf. Such a star would be the remnant of a former mass donor that was the source of the large spin angular momentum of Regulus itself.Comment: 18 pages, 2 figures, ApJL in pres

Informed consent in veterinary medicine: ethical implications for the profession and the animal 'patient'

Informed consent processes are a vital component of both human and veterinary medicine. Current practice encourages veterinarians to learn from insights in the human medical field about how best to achieve valid consent. However, drawing on published literature in veterinary and medical ethics, this paper identifies considerable differences between the purposes of veterinary and human medical consent. Crucially, it is argued that the legal status of animal patients as ‘property’ has implications for the ethical role of veterinary informed consent and the protection of the animal ‘patient’. It is suggested that veterinary informed consent should be viewed as an ethical pivot point where the multiple responsibilities of a veterinary professional converge. In practice, balancing these responsibilities creates considerable ethical challenges. As an example, the paper discusses the renewed call for UK veterinarians to make animal welfare their first priority; we predict that this imperative may increasingly cause veterinary informed consent to become an ethical pressure point due to tensions caused by the often conflicting interests of animals, owners and the veterinary profession. In conclusion, the paper argues that whilst gaining informed consent can often be presented as a robust ethical justification in human medicine, the same cannot be said in veterinary medicine. If the veterinary profession wish to prioritise animal welfare, there is an urgent need to re-evaluate the nature of authority gained through owner informed consent and to consider whether animal patients might need to be better protected outside the consent process in certain circumstances

Discrepancy Between Stone and Tissue Mineral Type in Patients with Idiopathic Uric Acid Stones

Objectives: To describe the papillary pathology found in uric acid (UA) stone formers, and to investigate the mineral form of tissue deposits. Materials and Methods: We studied eight UA stone formers treated with percutaneous nephrolithotomy. Papillae were imaged intraoperatively using digital endoscopy, and cortical and papillary biopsies were taken. Biopsies were analyzed by light microscopy, micro-CT, and microinfrared spectroscopy. Results: As expected, urine pH was generally low. UA supersaturation exceeded one in all but one case, compatible with the stone material. By intraoperative imaging, the renal papillae displayed a heterogeneous mixture of plaque and plugging, ranging from normal to severe. All patients had mineral in ducts of Bellini and inner medullary collecting ducts, mainly apatite with lesser amounts of urate and/or calcium oxalate in some specimens. Papillary and cortical interstitial tissue injury was modest despite the tubule plugging. No instance was found of a stone growing attached to either plaque or plugs. Conclusions: UA stone formers resemble those with ileostomy in having rather low urine pH while forming tubule plugs that contain crystals that can only form at pH values above those of their bulk urine. This discrepancy between tissue mineral deposits and stone type suggests that local tubular pH exceeds that of the bulk urine, perhaps because of localized tubule injury. The manner in which UA stones form and the discordance between tubule crystals and stone type remain open research questions

In Vivo Renal Tubule pH in Stone Forming Human Kidneys

Introduction: There is evidence that patients with a history of ileostomies who make acidic urine and form uric acid or calcium oxalate stones may plug some collecting ducts with calcium phosphate (CaP) and urate crystals. This is a paradoxical finding as such minerals should not form at an acid pH. One possible explanation is the presence of acidification defects due to focal damage to inner medullary collecting duct and duct of Bellini (BD) cells. We sought to further investigate this hypothesis through direct measurement of ductal pH in dilated Bellini ducts in patients with ileostomies undergoing percutaneous nephrolithotomy for stone removal. Methods: After obtaining IRB approval, we used a fiber-optic pH microsensor with a 140 µm diameter tip to measure intraluminal pH from the bladder, saline irrigant and dilated BD’s of patients undergoing PCNL. Results: Measurements were taken from three patients meeting inclusion criteria. Measured pH of bladder urine ranged from 4.97 – 5.58 and pH of saline irrigant used during surgery ranged from 5.17 – 5.75. BD measurements were achieved in 11 different BDs. Mean intraductal BD pH was more than 1 unit higher than bulk urine (6.43 ± 0.22 vs. 5.31 ± 0.22, p<0.01). Conclusions: This is the first evidence for focal acidification defects within injured/dilated BD of human kidneys producing a highly acidic bulk phase urine. These results may help explain the paradoxical finding of CaP and urate plugs in dilated ducts of patients with stone forming diseases characterized by highly acidic urine

Global value trees

The fragmentation of production across countries has become an important feature of the globalization in recent decades and is often conceptualized by the term “global value chains” (GVCs). When empirically investigating the GVCs, previous studies are mainly interested in knowing how global the GVCs are rather than how the GVCs look like. From a complex networks perspective, we use the World Input-Output Database (WIOD) to study the evolution of the global production system. We find that the industry-level GVCs are indeed not chain-like but are better characterized by the tree topology. Hence, we compute the global value trees (GVTs) for all the industries available in the WIOD. Moreover, we compute an industry importance measure based on the GVTs and compare it with other network centrality measures. Finally, we discuss some future applications of the GVTs