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•In 222 boys with severe hemophilia A and inhibitors of >5 BU, bleeding was reduced from 6.1 to 4.4 per year during ITI.•Before ITI, bleeding was independent of inhibitor titer; during ITI, bleeding increased with higher inhibitor titer and nondaily ITI.

Information on bleeding phenotype in non-severe hemophilia may be used to determine target factor levels for prophylaxis or gene therapy in severe hemophilia.

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Recommendations for management of cancer-related venous thromboembolism (VTE) in patients already receiving anticoagulant therapy are based on low-quality evidence. This international registry sought to provide more information on outcomes after a breakthrough VTE in relation to anticoagulation strategies.

The bleeding tendency and fear of bleeds may have a negative effect on preventive dental care of patients with haemophilia both at home and at dental appointments.To describe the clinical practice of dental care in children with haemophilia in Helsinki, Finland.This study evaluated retrospectively the medical records of 28 paediatric patients with haemophilia (aged 5.3–17.4 years) from dental visits during 2009–2010. Decayed, missing and filled teeth in the primary (dmft) and permanent dentition (DMFT), Community Periodontal Index (CPI), signs of developmental dental defects in enamel and the number of preventive and restorative procedures were gathered. Dmft + DMFT scores were compared with those of 17,079 non-haemophiliac boys. The Mann–Whitney U-test was used to compare the data between the groups of different severity of haemophilia.The median number of dental visits per patient was three (range 1–11). Twenty-two patients (79 %) had dmft + DMFT-scores within the 95 % reference range for age. None of the children had a CPI >2. Twelve (43 %) patients had developmental enamel defects. Half had received restorative dental care and three out of four preventive procedures.Dental care during hospital visits in children with haemophilia may enhance confidence in the preventive dental care and help minimise bleeding during dental procedures.

Ovulatory potential was studied during the use of two oral contraceptive pill preparations, after repeated mid-cycle administration of activated charcoal. Eleven women used monophasic pills containing gestodene, 75 microgram, plus ethinyl oestradiol, 30 microgram, or norethisterone acetate, 1 mg, plus ethinyl oestradiol, 30 microgram, for 4 months each, in randomized order. During both pill treatments the third cycle was a control cycle, and during the fourth cycle of both pill types, 5 g of activated charcoal was ingested four times a day, starting 3 h after pill intake, on cycle days 12, 13 and 14. Ovarian activity was monitored by intravaginal ultrasonography of follicles and by measurements of serum concentrations of LH, FSH, oestradiol and progesterone throughout the control and charcoal-treatment cycles of both pill treatments. None of the women ovulated. Follicular activity seen in two women did not correlate with charcoal administration. It is concluded that the possible enterohepatic recirculation of gestodene and norethisterone is not of clinical importance. Repeated charcoal treatment, when administered 3 h after but at least 12 h before pill intake, can be used to treat diarrhoea in women taking oral contraceptives.

Nestorone® (NES) progestin is highly effective for contraception following parenteral administration, but ineffective after oral ingestion due to rapid first-pass metabolism. Thus, NES might be ideal for lactational contraception; possible NES in milk should be metabolized by the nursing infant. We evaluated the distribution of NES, its endocrine effects and infant weight gain in five cynomolgus monkeys and their nursing infants. Nestorone® implants, releasing ~40 μg NES/day in vitro, were placed s.c. in the mothers 3–4 months following delivery, where they remained in situ for 4 weeks. Sampling (blood daily from the mother; milk and blood from the infant at 3 day intervals) was initiated at 2 weeks prior to insertion, and continued for 2 weeks following removal of the implant. NES, oestradiol, progesterone and prolactin were measured by radioimmunoassays and the infants were weighed weekly. The (mean ± SD) maternal serum and milk concentrations of NES were 337 ± 90 and 586 ± 301 pmol/l during the use of the implants. The ratio of milk/serum NES was 1.68 ± 0.12 (mean ± SE), and the serum and milk concentrations were significantly correlated (r = 0.75, P < 0.001). NES was not detectable (<13 pmol/l) in any infant serum samples. Concentrations of prolactin (mean ± SD) were 41.1 ± 32, 26.7 ± 7.6 and 26.3 ± 9.5 ng/ml before, during and after the use of the implants respectively. The (mean ± SE) infant weight increased from 643 ± 54 g 1 week prior to insertion to 713 ± 54 g 1 week following removal. These data confirm that NES in milk is rapidly metabolized by the suckling infant. Therefore, NES appears to be an ideal hormonal contraceptive for use during lactation.

Nestorone (NES) progestin is highly effective for contraception following parenteral administration, but ineffective after oral ingestion due to rapid first-pass metabolism. Thus, NES might be ideal for lactational contraception; possible NES in milk should be metabolized by the nursing infant. We evaluated the distribution of NES, its endocrine effects and infant weight gain in five cynomolgus monkeys and their nursing infants. Nestorone implants, releasing approximately 40 microg NES/day in vitro, were placed s.c. in the mothers 3-4 months following delivery, where they remained in situ for 4 weeks. Sampling (blood daily from the mother; milk and blood from the infant at 3 day intervals) was initiated at 2 weeks prior to insertion, and continued for 2 weeks following removal of the implant. NES, oestradiol, progesterone and prolactin were measured by radioimmunoassays and the infants were weighed weekly. The (mean +/- SD) maternal serum and milk concentrations of NES were 337 +/- 90 and 586 +/- 301 pmol/l during the use of the implants. The ratio of milk/serum NES was 1.68 +/- 0.12 (mean +/- SE), and the serum and milk concentrations were significantly correlated (r = 0. 75, P < 0.001). NES was not detectable (<13 pmol/l) in any infant serum samples. Concentrations of prolactin (mean +/- SD) were 41.1 +/- 32, 26.7 +/- 7.6 and 26.3 +/- 9.5 ng/ml before, during and after the use of the implants respectively. The (mean +/- SE) infant weight increased from 643 +/- 54 g 1 week prior to insertion to 713 +/- 54 g 1 week following removal. These data confirm that NES in milk is rapidly metabolized by the suckling infant. Therefore, NES appears to be an ideal hormonal contraceptive for use during lactation.

Progressive epilepsy with mental retardation (EPMR) is an autosomal recessive central nervous system disorder characterized by childhood onset epilepsy and subsequent mental retardation. The locus for EPMR has been mapped to human chromosome 8p23. We recently reported the construction of a YAC contig across the 4 centimorgan minimum genetic region that harbors the disease locus. We now report further delineation of the critical region to <700 kb. Our mapping strategy relied on the identification of nine novel microsatellite markers and the construction of a complete BAC contig across the critical region. Several partial gene sequences have been identified from the region and are being analyzed as candidate genes for EPMR.

A recently delineated childhood epilepsy has hitherto been observed only in a small geographic region in northern Finland, where, with the exception of one, both parents of all of the 11 sibships with affected individuals descend from one or two founding couples. The disease is characterized by generalized tonic-clonic seizures with onset at 5-10 years and progressive, severe mental retardation with onset 2-5 years after the first seizures. In this study the gene locus is assigned to the telomeric region of chromosome 8p by linkage. Analyses of recombinations place the locus in the 7-centimorgan interval between AFM185xb2 and D8S262 in which three markers, D8S504, D8S264, and AFM077yg5, show no recombinations with the phenotype. Haplotypes comprising alleles at the above five loci support the hypothesis of a single founding mutation for all affected chromosomes except the one belonging to the unrelated parent, who has a very different haplotype, suggesting another mutation or a very old ancestry of a single mutation. This study raises to three the number of heritable epilepsies whose gene loci have been mapped and provides a starting point for the cloning of the gene. It also suggests the possibility that the disease might not be limited to the northern Finnish population.

Fat-cells were isolated from patients of body-mass indices (BMIs) ranging from 17.9 to 83.9 kg/m2. Isoprenaline-stimulated cyclic AMP accumulation in cells prepared from obese subjects as compared with normal-weight subjects, was less sensitive to inhibition by the adenosine agonist N6-(phenylisopropyl)adenosine (PIA) (P = 0.047). The inhibition of 7 beta-desacetyl-7 beta-[gamma-(N-methylpiperazino) butyryl]-forskolin-stimulated adenylate cyclase by PIA in the presence of adenosine deaminase was also much attenuated in crude plasma membranes of adipocytes prepared from massively obese patients as compared with lean controls (P = 0.0143). This difference was probably not due to different cell size, because adenylate cyclase of crude plasma membranes of large adipocytes was actually more sensitive to PIA than was adenylate cyclase of membranes of smaller fat-cells co-isolated from the same individual. The stimulatory effect of PIA on glucose uptake in the presence of adenosine deaminase was depressed in adipocytes prepared from obese subjects and correlated with BMI at r = -0.626 (P = 0.007) at 100 nM-PIA. The adenosine receptors were studied by using the adenosine antagonist 1,3-[3H]dipropyl-8-cyclopentylxanthine. The binding was rapid and proportional to protein concentration. There was no difference in the affinities of receptors in membranes of obese and normal-weight subjects; Kd values of all patients averaged 3.3 nM. Bmax values were 54 and 130 fmol/mg of protein in membranes prepared from seven obese and five control patients respectively. The Bmax values calculated per mg of protein correlated with BMI at r = -0.539 (P = 0.047). The adenosine content of adipose tissue was higher in obese than in control subjects. These results demonstrate an attenuated response of cyclic AMP accumulation, adenylate cyclase and glucose uptake to adenosine in fat-cells prepared from obese subjects, and suggest that this change is at least partly due to changes in the amount of adenosine receptors, but not their affinity. The decreased receptor number could be due to higher adenosine content. A higher adenosine concentration in adipose tissue could explain why lipolysis is inhibited in situ in obesity, and the desensitization could explain the diminished response to adenosine analogues in isolated fat-cells.

Progressive epilepsy with mental retardation (EPMR) is an autosomal recessive central nervous system disorder characterized by childhood onset epilepsy and subsequent mental retardation. The locus for EPMR has been mapped to human chromosome 8p23. We recently reported the construction of a YAC contig across the 4 centimorgan minimum genetic region that harbors the disease locus. We now report further delineation of the critical region to <700 kb. Our mapping strategy relied on the identification of nine novel microsatellite markers and the construction of a complete BAC contig across the critical region. Several partial gene sequences have been identified from the region and are being analyzed as candidate genes for EPMR.

Changes in the amounts and functions of G-proteins have been reported in diabetic rats. We determined the Gi/Gs ratio of adipocyte plasma membranes in six insulinopenic diabetic patients and matched controls by immunoblotting with antisera against synthetic peptides corresponding to regions of G-proteins. No consistent changes in the Gi/Gs ratio were observed. It is still possible that the functional status of the G-proteins may be altered in diabetes.

We report on a 2085 nm holmium-doped silica fiber laser passively mode-locked by semiconductor saturable absorber mirror and carbon nanotube absorber. The laser, pumped by a 1.16 μm semiconductor disk laser, produces 890 femtosecond pulses with the average power of 46 mW and the repetition rate of 15.7 MHz.

A 1.6µm mode-locked Raman fiber laser pumped by a 1480nm semiconductor disk laser is demonstrated. Watt-level core pumping of the single-mode fiber Raman lasers with low-noise disk lasers together with semiconductor saturable absorber mirror mode locking represents a highly practical solution for short-pulse operation.

A 1.6µm mode-locked Raman fiber laser pumped by a 1480nm semiconductor disk laser is demonstrated. Watt-level core pumping of the single-mode fiber Raman lasers with low-noise disk lasers together with semiconductor saturable absorber mirror mode locking represents a highly practical solution for short-pulse operation.

Lactational amenorrhea ideally should provide a means of contraception to augment the interval between pregnancies, but its duration varies widely, and a considerable number of fully nursing mothers resume ovulating within 6 months of giving birth. Ideally, using a lactational hormonal contraceptive should be effective without causing problems in lactation or for the nursing infant. Nestorone (NES) is a good candidate, because its parenteral use would ensure effective contraception in nursing mothers and because the mother’s and infant’s liver should rapidly metabolize the hormone. This study evaluated NES in five cynomolgus monkeys and their nursing infants. Implants that release about 40 mg of NES daily in vitrowere implanted subcutaneously 3 to 4 months after delivery and were removed after 4 weeks. Levels of NES and other hormones were estimated by radioimmunoassay in blood and milk samples.

We analyze the effect of strain compensation on the crystalline quality of InGaAs/GaAs quantum well gain mirrors that are designed for emission above 1100 nm. The gain mirrors used in this study were grown by molecular beam epitaxy and they utilize GaAsP strain compensation. The effect of strain compensation has been assessed by measuring the curvature of the wafers and by mapping photoluminescence to identify non-emissive dark areas. We present that about 70 % strain compensation is sufficient to prevent dark line defect generation for gain mirrors designed for up to 1170 nm operation. Rapid thermal annealing studies revealed that the strain compensation is efficient in preventing appearance of dark lines even for samples that have been annealed at temperatures as high as 700 °C for a considerable time. Finally, we demonstrate multi-watt operation at 1115-1190 nm using 70-90 % strain compensated gain mirrors.