Playing mathematics.

We are used to thinking of mathematics as a symbolic activity. Here I argue that it may also be seen as a performative one. Making an analogy with music, I draw attention to the ways in which mathematics may not only be written down but also played out.

The mystery of our mathematical universe.

Why is it that fundamental laws discovered through pure mathematics have been able to describe the behavior of our physical world with such precision? Given that the physical universe is composed of mathematical properties, some have posited that mathematics is the language of the universe, whose laws reveal what appears to be a hidden order in the natural world. Physicist S. James Gates, Jr. and science writer Margaret Wertheim explore the uncanny ability of mathematics to reveal the laws of nature.

Cystine Stone Formers Have Impaired Health-Related Quality of Life Compared with Noncystine Stone Formers: A Case-Referent Study Piloting the Wisconsin Stone Quality of Life Questionnaire Among Patients with Cystine Stones.

INTRODUCTION: Cystinuria is a rare cause of urolithiasis. Affected patients have an earlier onset and more aggressive disease than patients with other stone etiologies. We assessed the health-related quality of life (HRQOL) of cystine stone-forming patients using the disease-specific Wisconsin Stone Quality of Life questionnaire (WISQOL). METHODS: Cystine patients treated in our stone clinics (n = 12) completed the WISQOL; information about medical and stone histories was gathered. Patients were matched with noncystine stone formers (n = 12) for gender, age, and comorbidities. In addition, a second control group (n = 90), also from our institution and consisting of mixed calcium stone formers, was included. WISQOL responses were compared between groups. RESULTS: Cystine patients had significantly lower total WISQOL scores than noncystine patients. Compared with noncystine stone formers, cystine stone formers also had lower HRQOL scores for subscales (domains) related to social impact, emotional impact, disease impact, and vitality (p ≤ 0.04 for all). On specific items, cystine patients reported significantly more sleep problems (p = 0.02), more bother with nocturia (p = 0.03), and feeling tired or fatigued (p = 0.02). Among those with current stones, cystine patients scored lower than noncystine patients for total score and in two of four domains. CONCLUSIONS: Using a stone-specific questionnaire, patients with cystine stones have lower HRQOL compared with noncystine stone formers. Identifying and addressing specific areas of decrement in patients with cystine stones may improve disease management and patients' HRQOL.

Alkali replacement raises urinary citrate excretion in patients with topiramate-induced hypocitraturia.

AIMS: The aims of this study were to assess (1) the magnitude and temporality of decreased urinary citrate excretion in patients just starting topiramate and (2) the effect of alkali replacement on topiramate-induced hypocitraturia. METHODS: Study 1 was a prospective, non-intervention study in which patients starting topiramate for headache remediation provided pre- and post-topiramate 24 h urine collections for measurement of urine citrate. Study 2 was a clinical comparative effectiveness study in which patients reporting to our stone clinic for kidney stones and who were treated with topiramate were prescribed alkali therapy. Pre- and post-alkali 24 h urinary citrate excretion was compared. RESULTS: Data for 12 and 22 patients (studies 1 and 2 respectively) were evaluated. After starting topiramate, urinary citrate excretion dropped significantly by 30 days (P = 0.016) and 62% of patients had hypocitraturia (citrate <320 mg day(-1) ). At 60 days, urine citrate was even lower than at baseline (P = 0.0032) and 86% of patients had developed hypocitraturia. After starting alkali, urine citrate increased in stone-forming patients on topiramate (198 ± 120 to 408 ± 274 mg day(-1) ; P = 0.042 for difference). 85% of patients were hypocitraturic on topiramate alone vs. 40% after adding alkali. The increase in urinary citrate was greater in patients provided ≥ 90 mEq potassium citrate. CONCLUSIONS: Our study is the first to provide clinical evidence that alkali therapy can raise urinary citrate excretion in patients who form kidney stones while being treated with topiramate. Clinicians should consider alkali therapy for reducing the kidney stone risk of patients benefitting from topiramate treatment for migraine headaches or other conditions.

Preliminary Evidence Suggests Periureteral Botulinum Toxin Type A Injection Improves Ureteral Stone Passage in the Porcine Model.

PURPOSE: We evaluated the use of periureteral injection of botulinum toxin type A (Botox(®), BTX-A) to facilitate passage of ureteral stones in a porcine model. We believe that reducing detrusor muscle tone around the intramural ureter may facilitate passage of ureteral stones through the ureterovesical junction. MATERIALS AND METHODS: With complete Institutional Animal Care and Use Committee approval, artificial stones (BegoStone plus) were placed by retrograde ureteroscopy into the proximal ureter using fluoroscopic guidance using an in-vivo porcine model. Six animals underwent periureteral BTX-A injection 30 U/mL to three locations around the ureteral orifice, and six animals were in the control group undergoing periureteral injection of physiologic saline. RESULTS: There was a significant decrease in time to stone passage in the BTX-A group compared with the control group, 2.6 ± 1.3 vs 6.8 ± 2.9 days, respectively (p = 0.018). None of the animals had evidence of vesicoureteral reflux postprocedure (N = 0/12). CONCLUSIONS: Preliminary results suggest that periureteral injection of BTX-A facilitates ureteral stone passage in this model. BTX-A may provide a simple, office-based endoscopic treatment option for ureteral stones. Further studies would be necessary to evaluate its efficacy in humans compared with traditional medical expulsive therapy.

Current practice patterns of urologists providing nutrition recommendations to patients with kidney stones.

OBJECTIVE: To assess urologists' practice patterns and beliefs about dietary therapy for stone prevention. Dietary therapy is offered to stone formers (SFs) by a subset of urologists. While some may involve a registered dietitian (RD) to provide medical nutrition therapy (MNT), most do not as MNT is Medicare-covered only for diabetes and chronic kidney disease. MATERIALS AND METHODS: An investigator-created survey was distributed to assess Endourological Society members' opinions, confidence, and practices regarding nutrition therapy. RESULTS: Respondents (n=217) practice largely in academic, hospital/clinic, and private settings. Most (82%) felt dietary therapy should be provided regardless of the number of stone events. Most (90%) said the urologist should provide dietary recommendations and more than half (52%) do so for ≥75% of patients (10% provide it for <25%). Time spent with SFs for nutrition varied from ≤4 to ≥10 minutes (31% and 23%) with 64% feeling this to be insufficient time. Of urologists providing counseling, 58% assess their patients' diets. Self-confidence in determining dietary contributors to risk factors and in quantifying intake of foods/nutrients varied (range 45%-82%). Most (76%) said they would like another provider to give recommendations; 23% partner with an RD to do so. CONCLUSIONS: Urologists are interested in dietary stone prevention, despite the fact that the majority have inadequate time to provide it. We identified areas of educational need, specifically, quantifying patients' intake of certain foods/nutrients and identifying whether stone risk factors are diet related. Urologists' skill gaps are precisely the strengths of RDs, and thus, a partnership between RDs and urologists could be beneficial.

Crk-associated substrate (Cas) family member, NEDD9, is regulated in human neuroblastoma cells and in the embryonic hindbrain by all-trans retinoic acid.

The vitamin A metabolite, all-trans retinoic acid (atRA), plays an essential role in vertebrate embryogenesis, including development of the nervous system. In the human neuroblastoma cell line, SH-SY5Y, atRA rapidly induces (within 4 hr) the expression of the Crk-associated substrate (Cas) family member, neural precursor cell-expressed, developmentally down-regulated gene 9 (NEDD9) also called the human enhancer of filamentation (HEF1). NEDD9 is expressed in the developing hindbrain (5-somite stage) in the presumptive rhombomeres 2, 3, and 5 before the onset of overt segmentation. Exposure of rat embryos to excess atRA at times ranging from E9.25 to E12 leads to altered NEDD9 expression in the developing hindbrain within 6 hr. NEDD9 expression is also perturbed in vitamin A-deficient embryos. A putative retinoic acid response element in the 5' region of the NEDD9 promoter binds specifically to a RXR/RAR heterodimer and forms a higher molecular weight complex upon addition of a retinoic acid receptor-specific antibody. Regulation of NEDD9 may be an important means whereby atRA promotes cell spreading and neurite outgrowth in SH-SY5Y human neuroblastoma cells, and NEDD9 represents a new downstream target of atRA and its receptors in the developing hindbrain.