Characterisation and feasibility study for superradiant lasing in 40Ca atoms.

Superradiant active clocks operating on narrow linewidth clock transitions are predicted to achieve precision orders of magnitude higher than any currently existing optical atomic clocks. We introduce a theory of superradiant lasing and implement it for the example of 40Ca atoms. The presented model, however, is valid for any two- or three-level system in an optical lattice. We perform a feasibility analysis and suggest a set of parameters for the experimental fulfillment of superradiant lasing in Ca. Moreover, we present an overview of different magic wavelengths for the 4s2 1S0 ↔ 4s4p3P1 (mJ = 0) transition in Ca for different polarizations and a robustness analysis of these magic conditions. We also report the magic-zero wavelengths for the 4s4p3P1, mJ = 0 state.

New bounds on dark matter coupling from a global network of optical atomic clocks.

We report on the first Earth-scale quantum sensor network based on optical atomic clocks aimed at dark matter (DM) detection. Exploiting differences in the susceptibilities to the fine-structure constant of essential parts of an optical atomic clock, i.e., the cold atoms and the optical reference cavity, we can perform sensitive searches for DM signatures without the need for real-time comparisons of the clocks. We report a two orders of magnitude improvement in constraints on transient variations of the fine-structure constant, which considerably improves the detection limit for the standard model (SM)-DM coupling. We use Yb and Sr optical atomic clocks at four laboratories on three continents to search for both topological defect and massive scalar field candidates. No signal consistent with a DM coupling is identified, leading to considerably improved constraints on the DM-SM couplings.

Arthroscopic knee anatomy in young achondroplasia patients.

PURPOSE: Achondroplasia is the most common form of skeletal dysplasia, affecting more than 250 000 individuals worldwide. In these patients, the developing knee undergoes multiple anatomical changes. The purpose of this study was to characterise the intra-articular knee anatomy in children with achondroplasia who underwent knee arthroscopy. METHODS: Records of achondroplasia patients who underwent knee arthroscopy between 2009 and 2014 were reviewed. Demographic data, operative reports, follow-up notes, MRI and arthroscopy images were reviewed. Bony, cartilaginous and ligamentous changes were noted. The trochlea sulcus angle was measured from intra-operative arthroscopic images. RESULTS: A total of 12 knee arthroscopies in nine patients were performed. The mean age at surgery was 16.9 years (12 to 22). In all patients, the indication for surgery was knee pain and/or mechanical symptoms that were refractory to non-operative treatment. Three anatomical variations involving the distal femur were found in all knees: a deep femoral trochlea; a high A-shaped intercondylar notch; and a vertically oriented anterior cruciate ligament. The average trochlea sulcus angle measured 123°. Pathology included: synovial plica (one knee); chondral lesions (three knees); discoid lateral meniscus (11 knees); and meniscal tears (six knees). All patients were pain-free and returned to normal activity at final follow-up. CONCLUSION: Children with achondroplasia have characteristic distal femur anatomy noted during knee arthroscopy. These variations should be considered normal during knee arthroscopy in these patients. Arthroscopic findings confirmed previous MRI findings within this specific population with the addition of a deep trochlear groove which was not previously reported.

Re-alignment and intramedullary rodding of the humerus and forearm in children with osteogenesis imperfecta: revision rate and effect on fracture rate.

PURPOSE: Intramedullary rodding is indicated for patients with osteogenesis imperfecta (OI) to manage deformity and help treat recurrent fractures. Historically, the focus of intramedullary stabilisation has been the lower extremity. Here we report our experience of intramedullary rodding of the humerus and forearm in children with OI and its impact on the fracture rate of those bone segments. PATIENTS AND METHODS: This is a retrospective chart review of all OI patients who have undergone re-alignment and intramedullary rodding of the humerus or forearm between October 1994 and February 2016. Patient demographics, surgical information, complications and pre-operative and post-operative fracture rates were gathered. RESULTS: A total of 45 upper extremity segments (26 humeri, 19 forearms) were rodded at an average age of 8.7 years (3.1 to 19.2). Of these, 15 (33.3%) of the bone segments required a return to the operating room at a mean 30.8 months (1 to 90) post-operatively. Fracture data was available for 24 of the bone segments. The average number of pre-operative and post-operative fractures was 3.58 (SD 2.84) and 0.46 (SD 0.72) respectively. The average pre-operative and post-operative fracture rates were 0.87 fractures/year (SD 0.47) and 0.10 fractures/year (SD 0.16) respectively. CONCLUSION: In this OI population, re-alignment and rodding appeared to reduce the fracture rate of the humerus and forearm. Among our population, one third returned to the operating room and one fifth required revision to a new intramedullary implant. This data may help families better understand the potential outcomes of upper extremity realignment and rodding and its effect on the rate of upper extremity fractures.

Cesarean delivery is not associated with decreased at-birth fracture rates in osteogenesis imperfecta.

PURPOSE: Osteogenesis imperfecta (OI) predisposes to recurrent fractures. Patients with the moderate to severe forms of OI present with antenatal fractures, and the mode of delivery that would be safest for the fetus is not known. METHODS: We conducted systematic analyses of the largest cohort of individuals with OI (n = 540) enrolled to date in the OI Linked Clinical Research Centers. Self-reported at-birth fracture rates were compared among individuals with OI types I, III, and IV. Multivariate analyses utilizing backward-elimination logistic regression model building were performed to assess the effect of multiple covariates, including method of delivery, on fracture-related outcomes. RESULTS: When accounting for other covariates, at-birth fracture rates did not differ based on whether delivery was by vaginal route or by cesarean delivery (CD). Increased birth weight conferred higher risk for fractures irrespective of the delivery method. In utero fracture, maternal history of OI, and breech presentation were strong predictors for choosing CD. CONCLUSION: Our study, the largest to analyze the effect of various factors on at-birth fracture rates in OI, shows that CD is not associated with decreased fracture rate. With the limitation that the fracture data were self-reported in this cohort, these results suggest that CD should be performed only for other maternal or fetal indications, not for the sole purpose of fracture prevention in OI.Genet Med 18 6, 570-576.

A cross-sectional multicenter study of osteogenesis imperfecta in North America - results from the linked clinical research centers.

Osteogenesis imperfecta (OI) is the most common skeletal dysplasia that predisposes to recurrent fractures and bone deformities. In spite of significant advances in understanding the genetic basis of OI, there have been no large-scale natural history studies. To better understand the natural history and improve the care of patients, a network of Linked Clinical Research Centers (LCRC) was established. Subjects with OI were enrolled in a longitudinal study, and in this report, we present cross-sectional data on the largest cohort of OI subjects (n = 544). OI type III subjects had higher prevalence of dentinogenesis imperfecta, severe scoliosis, and long bone deformities as compared to those with OI types I and IV. Whereas the mean lumbar spine area bone mineral density (LS aBMD) was low across all OI subtypes, those with more severe forms had lower bone mass. Molecular testing may help predict the subtype in type I collagen-related OI. Analysis of such well-collected and unbiased data in OI can not only help answering questions that are relevant to patient care but also foster hypothesis-driven research, especially in the context of 'phenotypic expansion' driven by next-generation sequencing.

The serum level of fibroblast growth factor-23 and calcium-phosphate homeostasis in obese perimenopausal women.

Plasma FGF-23 concentrations and its relationship with calcium-phosphate homeostasis were evaluated in 48 perimenopausal obese women and in 29 nonobese controls. Serum parathyroid hormone, 25-hydroxyvitamin D(3), CTX1, osteocalcin, total calcium, phosphorus, creatinine, and plasma intact FGF-23 concentrations were assessed. DXA of lumbar spine and femoral neck was performed to determine bone mineral density (BMD). Plasma iFGF-23 concentration was significantly higher in obese patients (by 42%) and correlated with age and BMD of proximal femur (R = -0.346; R = 0.285, resp.) but not with markers of bone turnover. However, serum phosphorus level in obese subjects was significantly lower. iFGF-23 concentration correlated significantly with body mass index (R = 0.292) and fat content (R = 0.259) in all study subjects. Moreover, a significant correlation between iFGF-23 and iPTH (R = 0.254) was found. No correlation between serum phosphorus or eGFR and plasma iFGF-23 and between eGFR and serum phosphorus was found. Elevated serum iFGF-23 concentration may partially explain lower phosphorus levels in the obese and seems not to reflect bone turnover.

Obstructive hypertrophic cardiomyopathy is associated with enhanced thrombin generation and platelet activation.

OBJECTIVES: To investigate the association of left ventricular outflow tract (LVOT) obstruction with blood coagulation, platelet activity and inflammatory response in patients with hypertrophic cardiomyopathy (HCM) and sinus rhythm. PATIENTS AND MAIN OUTCOME MEASURES: In 42 patients with HCM with sinus rhythm, including 16 patients with resting LVOT obstruction (gradient > or = 30 mm Hg) and 29 age- and sex-matched controls, markers of thrombin generation (thrombin-antithrombin complex (TAT), prothrombin fragment 1+2 (F1+2)), platelet activation (soluble CD40 ligand (sCD40L), beta-thromboglobulin (beta-TG), P-selectin) and inflammation (C-reactive protein (CRP), interleukin (IL)6, tumour necrosis factor-alpha (TNFalpha)) were determined. RESULTS: Thrombin, platelet and inflammatory markers were higher in the entire HCM group than in controls (p<0.005 for all compared parameters). Compared with non-obstructive HCM, obstructive HCM was associated with increased thrombin formation (TAT, F1+2), platelet activation (sCD40L, beta-TG, P-selectin) and both CRP and IL6 levels. Only the level of TNFalpha was similar in both forms of HCM. In contrast, a comparison of non-obstructive HCM with controls showed that all these variables (except for P-selectin) were similar; P-selectin was higher in non-obstructive HCM. The LVOT gradient correlated positively with all the raised blood markers (r from 0.39 to 0.73; p<0.05), except for TNFalpha. In multiple regression analysis models, the LVOT gradient was the only independent predictor of TAT (R(2) = 0.61; p<0.001), sCD40L (R(2) = 0.59; p<0.001), F1+2 (R(2) = 0.55; p = 0.002), P-selectin (R(2) = 0.49; p = 0.004) and beta-TG (R(2) = 0.38; p = 0.005) in patients with HCM. CONCLUSIONS: LVOT obstruction is independently associated with enhanced thrombin generation and platelet activity in patients with HCM with sinus rhythm.

The effect of intravenous pamidronate on bone mineral density, bone histomorphometry, and parameters of bone turnover in adults with type IA osteogenesis imperfecta.

The type IA osteogenesis imperfecta (OI) phenotype is characterized by multiple fractures, blue sclerae, and minimal skeletal deformity without dentinogenesis imperfecta. The object of this study was to determine the effect of treatment with intravenous pamidronate (30 mg) every 3 months on bone density and bone histomorphometry in adults with type IA OI. After an initial iliac crest bone biopsy eight subjects, 5 women and 3 men, entered a treatment program lasting 21-30 months. Five subjects, all women, completed the study which included a posttreatment iliac crest bone biopsy. Pamidronate treatment led to significant increases in bone mineral density (BMD), measured by DXA, in the lumbar spine at 12 months (P = 0.05) and in the femur neck (P = 0.02) at 24 months. Significant increases in BMD were also seen in femoral trochanter at 12 months (P = 0.05) and at 24 months (P = 0.02), and in Ward's triangle at 12 months (P = 0.02) and 24 months (P = 0.05). Mean osteocalcin levels decreased 32%, C-terminal procollagen peptide and bone alkaline phosphatase declined 12% and 47% at 15 and 21 months, respectively. Deoxypyridinoline crosslink excretion decreased 31%. Posttreatment bone biopsy revealed a significant 6.3% increase in mean bone trabecular volume (P = 0.01). Mean cortical thickness increased from 848 mm to 1384 mm (P = 0.01) and cortical porosity decreased 13.2% (P = 0.01). Bone formation rate increased significantly in all 5 patients from 6.6 to 15.3 mm2/yr (P = 0.01). Mineral apposition rate was unchanged. These results indicate that intravenous pamidronate, 30 mg every 3 months, may have significant effects on bone density and histomorphometry in adults with type IA OI. Responses at higher doses remain to be evaluated.

Photoperiod and temperature interact to affect the GnRH neuronal system of male prairie voles (Microtus ochrogaster).

Individuals of numerous species limit energy expenditure during winter by inhibiting reproduction and other nonessential functions. To time these adaptations appropriately with the annual cycle, animals rely on environmental cues that predict, well in advance, the onset of winter. The most commonly studied environmental factor that animals use to time reproduction is photoperiod. Rodents housed in short photoperiods in the laboratory or in naturally declining day lengths exhibit pronounced alterations in reproductive function concomitant with alterations in the hypothalamic gonadotropin-releasing hormone neuronal system. Because animals in their natural environment use factors in addition to photoperiod to time reproduction, the present study sought to determine the independent effects of photoperiod and temperature, as well as the interaction between these factors, on reproductive parameters and the GnRH neuronal system. Male prairie voles were housed in either long (LD 16:8) or short (LD 8:16) day lengths for 10 weeks. Animals in each photoperiod were further subdivided into groups housed in either mild (i.e., 20 degrees C) or low (i.e., 8 degrees C) temperatures. As shown with immunohistochemistry, voles that underwent gonadal regression in response to short photoperiods and long-day voles housed in low temperatures (and maintained large gonads) exhibit higher GnRH-immunoreactive (GnRH-ir) neuron numbers in the preoptic area/anterior hypothalamus (POA/AH) relative to all other groups. In addition, voles that underwent gonadal regression in response to both short days and low temperatures did not exhibit an increase in GnRH-ir neuron numbers compared to long-day, mild-temperature controls. These data suggest that photoperiod and temperature interact to influence reproductive function potentially by alterations of the GnRH neuronal system.

Retinoic acid receptor beta expression and growth inhibition of gynecologic cancer cells by the synthetic retinoid N-(4-hydroxyphenyl) retinamide.

BACKGROUND: The synthetic retinoid N-(4-hydroxyphenyl) retinamide (4HPR) can inhibit the growth of tumor cells. Preliminary results from a clinical trial suggest that 4HPR may reduce ovarian cancer incidence. We examined the growth-inhibitory effects of 4HPR on gynecologic cancer cell lines in vitro and the role of retinoid receptors in modulating this effect. METHODS: Twelve human gynecologic cancer cell lines (the ovarian cell lines--A224, AD10, UCI 101, UCI 107, SKOV3, 222, CP70, ML3B, and ML5; the cervical cell lines--HT3 and ME180; and the endometrial cell line--Hec 1A were tested for sensitivity to 4HPR (by assaying cell proliferation rates). Gel electrophoretic analysis of DNA fragmentation was used to measure programmed cell death (apoptosis). Specific retinoid receptor (retinoic acid receptor [RAR] and retinoid X receptor) messenger RNA (mRNA) levels were measured by northern blot hybridization. AD10 cells were stably transfected with human RARbeta complementary DNA, and the effect of 4HPR on cell proliferation was examined. RESULTS: 4HPR inhibited the growth of all 12 cell lines, but to varying degrees; IC50 values (i.e., concentrations that inhibit proliferation by 50%) ranged from 0.3 to 9 microM. Following 4HPR treatment, ovarian cancer cells that were sensitive to 4HPR (222, CP70, and UCI 101; IC50 <3 microM) contained higher levels of RARbeta transcripts than more resistant cells (AD10, ME180, Hec 1A, and A224; IC50 > or =3 microM) (2.8-fold; two-sided P = .006). Anchorage-independent growth of transfected AD10 cells expressing high levels of RARbeta was totally abolished, even in the absence of 4HPR; transfectants expressing low levels of RARbeta exhibited lower levels of anchorage-independent growth and grew more slowly in the presence of 4HPR than control untransfected AD10 cells. CONCLUSION: 4HPR inhibited the proliferation of ovarian cancer cells in vitro; RARbeta expression appeared to be associated with this effect.

The association between alcohol and breast cancer: popular press coverage of research.

OBJECTIVES: This study was undertaken to examine popular press reports of the association between alcohol and breast cancer. METHODS: Articles from scientific journals and stories from newspapers and magazines published from January 1, 1985, to July 1, 1992, were retrieved from six on-line databases. Lay press stories were analyzed to determine which medical articles were publicized and what information was reported. RESULTS: Fifty-eight scientific articles on the relationship of alcohol and breast cancer were found, and 64 newspaper and 23 magazine stories were retrieved. The press cited 11 studies, 19% of those published during the study period. Three studies were featured in 77% of popular press stories. No scientific review articles were reported. Behavioral recommendations were given to the public in 63% of stories. CONCLUSIONS: The vast majority of scientific studies on alcohol and breast cancer were ignored in press reports. We encourage researchers and the popular press to give the public a broader understanding of public health issues.

Direct mechanomyographic measurement of the myorelaxant action of baclofen and diazepam in normal and reserpinized rats.

A pathologically increased muscle tone is frequently observed. Objective methods for measuring directly the muscle-relaxant action of drugs in laboratory animals are scarce. This study shows that a computerized mechanomyographic method allows the assessment of myorelaxant drugs. The method consists of the successive bending and straightening of the rat's foot in the ankle joint and the separate measurement of resistance of extensors and flexors of the hind foot to passive movements. The two well-known antispastic drugs diazepam and baclofen reduced the normal muscle tone in both groups of muscles in non-treated animals as well as the muscle tone increased by reserpine (10 mg/kg i.p.). The results obtained show that the mechanomyographic method directly and reliably reveals the myorelaxant action of drugs.

A competitive enzyme-linked immunosorbent assay (ELISA) to detect retronecine and monocrotaline in vitro.

Antibodies to the nonesterified pyrrolizidine nucleus, retronecine (155 mol.wt), were produced in rabbits and detected using an avidin-biotin antibody ELISA. A competitive ELISA for the detection of retronecine and the cyclic diester monocrotaline was also developed using the antiserum produced against the hapten conjugate, retronecine-bovine serum albumin. Retronecine was obtained by hydrolysis of monocrotaline, succinylated and directly coupled to bovine serum albumin or ovalbumin. Antibodies to the pyrrolizidine nucleus, retronecine, can be detected within 5 min after the addition of substrate using the avidin-biotin ELISA. Competitive inhibition of antibodies to retronecine is obtained by the addition of known amounts (0-11.42 micrograms/microliters) of either the homologous antigen, retronecine, or the heterologous antigen, monocrotaline, however, retronecine acts as the better competitor.

Rapid decline in blood antimyotoxin levels in the presence of myotoxin A from prairie rattlesnake (Crotalus viridis viridis) venom.

The disappearance of antibodies to myotoxin a from the bloodstream in mice was measured with a specific ELISA over a ninety-six hour period in the presence and absence of myotoxin a. A gradual disappearance of antibodies to myotoxin in the absence of toxin was observed during the 96 hr sampling period, although antibodies were still detectable at 96 hrs. However, in the presence of myotoxin a very rapid decrease of antimyotoxin occurred. When antiserum injection was followed by myotoxin injection (5 min. later) the decline in antibodies was immediate and no antibodies could be detected 30 min. after the antiserum injection. When antiserum was injected either immediately or 30 min. after toxin, antibody levels declined sharply and were non-detectable 1 hr. after antiserum injection. These results have clinical significance since they indicate that antimyotoxin can still bind the toxin, even when administration of the antiserum is delayed for 30 min. after injection of the toxin. Multiple injections of antiserum may be required to maintain a neutralizing level of antiserum.

Detection of myotoxin alpha-like proteins in various snake venoms.

Ninety-five venom samples from eight snake genera (Agkistrodon, Bitis, Bothrops, Calloselasma, Crotalus, Sistrurus, Naja and Vipera) including venoms of Crotalus species of different geographical origin were assayed using immunodiffusion or an ELISA for the presence of the small basic protein, myotoxin alpha, known to cause muscle necrosis. Of the eight genera investigated, only Crotalus and Sistrurus venoms contained detectable amounts of myotoxin alpha-like proteins. The venoms of 13 out of 17 rattlesnake species investigated contained proteins immunologically similar to myotoxin alpha, including 12 Crotalus species and one Sistrurus species. The highest amounts were detected in venoms of C. exsul, C. viridis oreganus and C. v. viridis. Qualitative differences in the presence or absence of myotoxin alpha-like proteins were observed in the venoms of C. cerastes, C. horridus, C. lepidus, C. mitchelli, C. scutulatus, C. viridis and S. catenatus specimens of different geographic origin. The toxin was not detected in the venoms obtained from C. adamanteus, C. atrox, C. enyo or C. vegrandis specimens. The toxin appears to be widely distributed among rattlesnake species in the new world, but may vary qualitatively by geographical region in several species and subspecies.

Use of affinity-purified antibodies to measure the in vivo disappearance of antibodies to myotoxin a.

Antiserum against myotoxin a was purified using affinity chromatography. Myotoxin a was conjugated to an Affi-Gel agarose gel bead support and crude antiserum applied to the column. Antibody was eluted with distilled water, acetic acid and phosphate-buffered saline, and the protein concentration in the effluent was estimated by the absorbance at 280 nm. Antibody eluted with distilled water was used to develop an ELISA to detect antibodies to myotoxin in the bloodstream. Mice were injected with either 0.10, 0.15 or 0.20 ml of crude antiserum, and blood samples were taken during a four-week period. Samples were assayed for antimyotoxin using the antibody detection ELISA. Blood levels of antimyotoxin decreased significantly (P less than 0.05) within 1 hr after mice received 0.10 ml of crude antiserum (i.v.). Levels of antimyotoxin in mice given 0.15 and 0.20 ml of antiserum decreased significantly at 3 hr after the injection. Mice given 0.20 ml antiserum had significantly (P less than 0.05) higher amounts of antimyotoxin than mice receiving 0.10 ml antiserum during the 24-hr period after injection. However, after 24 hr all three treatment groups had less than 100 ng antimyotoxin/ml and did not differ significantly from one another. Measurement of antivenom in the bloodstream of snakebite patients might help determine if and when additional antivenom should be administered.

Blood acetyl- and butyrylcholinesterases in senile dementia of Alzheimer type.

The major neurochemical abnormality described to date in senile dementia of the Alzheimer type (SDAT) is a central cholinergic deficit. To determine whether this central deficit is reflected by changes in the levels of blood cholinesterases, plasma and erythrocyte acetylcholinesterase (AChE) and plasma butyrylcholinesterase (BChE), were measured in SDAT and other psychiatric disorders. Plasma AChE, which has only recently been described in human blood, was significantly elevated (P less than 0.01) in the SDAT group compared with the control and other clinical groups investigated. In contrast there were no significant differences in the activities of either erythrocyte AChE or plasma BChE between any of the clinical groups. Although the source of plasma AChE is unknown the possibility that some portion originates from the central nervous system and that the elevated AChE levels in SDAT reflect increased release from degenerating cholinergic neurons is discussed.

Prolactin and its involvement in fluid regulation in the bovine.

Plasma prolactin (PRL) concentrations, osmolality, water consumption, feed intake, urine excretion, and fecal water output were determined in twelve steers of 3 breeds exposed to 5 feed and water regimes. Breed differences were found in water intake and plasma PRL concentrations when feed and water were ad lib., however, during any of the other 4 treatments, responses were similar between breeds. During dehydration and feed restriction, water intake, urine, fecal water, and plasma prolactin decreased; however, during hydration and refeeding such changes were not as clearly related. No consistent relationships between plasma prolactin and osmolality were found. Data suggests that PRL's role in fluid regulation in the bovine is most likely associated with alterations in renal hemodynamics rather than by changes in plasma osmolality.