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Understanding and improving obstetrical quality and safety is an important goal of professional societies, and many interventions such as checklists, safety bundles, educational interventions, or other culture changes have been implemented to improve the quality of care provided to obstetrical patients. Although many factors contribute to delivery decisions, a reduced workload has addressed how provider issues such as fatigue or behaviors surrounding impending shift changes may influence the delivery mode and outcomes.The objective was to assess whether intrapartum obstetrical interventions and adverse outcomes differ based on the temporal proximity of the delivery to the attending's shift change.This was a secondary analysis from a multicenter obstetrical cohort in which all patients with cephalic, singleton gestations who attempted vaginal birth were eligible for inclusion. The primary exposure used to quantify the relationship between the proximity of the provider to their shift change and a delivery intervention was the ratio of time from the most recent attending shift change to vaginal delivery or decision for cesarean delivery to the total length of the shift. Ratios were used to represent the proportion of time completed in the shift by normalizing for varying shift lengths. A sensitivity analysis restricted to patients who were delivered by physicians working 12-hour shifts was performed. Outcomes chosen included cesarean delivery, episiotomy, third- or fourth-degree perineal laceration, 5-minute Apgar score of4, and neonatal intensive care unit admission. Chi-squared tests were used to evaluate outcomes based on the proportion of the attending's shift completed. Adjusted and unadjusted logistic models fitting a cubic spline (when indicated) were used to determine whether the frequency of outcomes throughout the shift occurred in a statistically significant, nonlinear pattern RESULTS: Of the 82,851 patients eligible for inclusion, 47,262 (57%) had ratio data available and constituted the analyzable sample. Deliveries were evenly distributed throughout shifts, with 50.6% taking place in the first half of shifts. There were no statistically significant differences in the frequency of cesarean delivery, episiotomy, third- or fourth-degree perineal lacerations, or 5-minute Apgar scores of4 based on the proportion of the shift completed. The findings were unchanged when evaluated with a cubic spline in unadjusted and adjusted logistic models. Sensitivity analyses performed on the 22.2% of patients who were delivered by a physician completing a 12-hour shift showed similar findings. There was a small increase in the frequency of neonatal intensive care unit admissions with a greater proportion of the shift completed (adjusted P=.009), but the findings did not persist in the sensitivity analysis.Clinically significant differences in obstetrical interventions and outcomes do not seem to exist based on the temporal proximity to the attending physician's shift change. Future work should attempt to directly study unit culture and provider fatigue to further investigate opportunities to improve obstetrical quality of care, and additional studies are needed to corroborate these findings in community settings.

Aggregation of TAR-DNA-binding protein 43 (TDP-43) and of its fragments TDP-25 and TDP-35 occurs in amyotrophic lateral sclerosis (ALS). TDP-25 and TDP-35 act as seeds for TDP-43 aggregation, altering its function and exerting toxicity. Thus, inhibition of TDP-25 and TDP-35 aggregation and promotion of their degradation may protect against cellular damage. Upregulation of HSPB8 is one possible approach for this purpose, since this chaperone promotes the clearance of an ALS associated fragments of TDP-43 and is upregulated in the surviving motor neurones of transgenic ALS mice and human patients. We report that overexpression of HSPB8 in immortalized motor neurones decreased the accumulation of TDP-25 and TDP-35 and that protection against mislocalized/truncated TDP-43 was observed for HSPB8 in Drosophila melanogaster. Overexpression of HSP67Bc, the functional ortholog of human HSPB8, suppressed the eye degeneration caused by the cytoplasmic accumulation of a TDP-43 variant with a mutation in the nuclear localization signal (TDP-43-NLS). TDP-43-NLS accumulation in retinal cells was counteracted by HSP67Bc overexpression. According with this finding, downregulation of HSP67Bc increased eye degeneration, an effect that is consistent with the accumulation of high molecular weight TDP-43 species and ubiquitinated proteins. Moreover, we report a novel Drosophila model expressing TDP-35, and show that while TDP-43 and TDP-25 expression in the fly eyes causes a mild degeneration, TDP-35 expression leads to severe neurodegeneration as revealed by pupae lethality; the latter effect could be rescued by HSP67Bc overexpression. Collectively, our data demonstrate that HSPB8 upregulation mitigates TDP-43 fragment mediated toxicity, in mammalian neuronal cells and flies.

BACKGROUND: While there are well-accepted standards for the diagnosis of arrested active-phase labor, the definition of a "failed" induction of labor remains less certain. One approach to diagnosing a failed induction is based on the duration of the latent phase. However, a standard for the minimum duration that the latent phase of a labor induction should continue, absent acute maternal or fetal indications for cesarean delivery, remains lacking. OBJECTIVE: The objective of this study was to determine the frequency of adverse maternal and perinatal outcomes as a function of the duration of the latent phase among nulliparous women undergoing labor induction. METHODS: This study is based on data from an obstetric cohort of women delivering at 25 U.S. hospitals from 2008-2011. Nulliparous women who had a term singleton gestation in the cephalic presentation were eligible for this analysis if they underwent a labor induction. Consistent with prior studies, the latent phase was determined to begin once cervical ripening had ended, oxytocin was initiated and rupture of membranes (ROM) had occurred, and was determined to end once 5 cm dilation was achieved. The frequencies of cesarean delivery, as well as of adverse maternal (e.g., cesarean delivery, postpartum hemorrhage, chorioamnionitis) and perinatal outcomes (e.g., a composite frequency of either seizures, sepsis, bone or nerve injury, encephalopathy, or death), were compared as a function of the duration of the latent phase (analyzed with time both as a continuous measure and categorized in 3-hour increments). RESULTS: A total of 10,677 women were available for analysis. In the vast majority (96.4%) of women, the active phase had been reached by 15 hours. The longer the duration of a woman's latent phase, the greater her chance of ultimately undergoing a cesarean delivery (P

The high specific activity tritiation of (+)-SKF-10,047 (1) and N,N-dimethyltryptamine (4) is described. [N-allyl-3H] (+)-SKF-10,047 (3) was prepared by Lindlar catalyst tritiation of (+)-N-propargylnormetazocine (2) and [N-methyl-3H] N,N-dimethyltryptamine (6) was synthesized by the alkylation of N-methyltryptamine (5) with [3H] methyl iodide. Both sigma-1 synthetic agonist 3 and endogenous agonist 6 have been useful in studying this receptor.

Background Studies of early-term birth after demonstrated fetal lung maturity show that respiratory and other outcomes are worse with early-term birth (370–386 weeks) even after demonstrated fetal lung maturity when compared with full-term birth (390–406 weeks). However, these studies included medically indicated births and are therefore potentially limited by confounding by the indication for delivery. Thus, the increase in adverse outcomes might be due to the indication for early-term birth rather than the early-term birth itself. Objective We examined the prevalence and risks of adverse neonatal outcomes associated with early-term birth after confirmed fetal lung maturity as compared with full-term birth in the absence of indications for early delivery. Study Design This is a secondary analysis of an observational study of births to 115,502 women in 25 hospitals in the United States from 2008 through 2011. Singleton nonanomalous births at 37–40 weeks with no identifiable indication for delivery were included; early-term births after positive fetal lung maturity testing were compared with full-term births. The primary outcome was a composite of death, ventilator for ≥2 days, continuous positive airway pressure, proven sepsis, pneumonia or meningitis, treated hypoglycemia, hyperbilirubinemia (phototherapy), and 5-minute Apgar Results In all, 48,137 births met inclusion criteria; the prevalence of fetal lung maturity testing in the absence of medical or obstetric indications for early delivery was 0.52% (n = 249). There were 180 (0.37%) early-term births after confirmed pulmonary maturity and 47,957 full-term births. Women in the former group were more likely to be non-Hispanic white, smoke, have received antenatal steroids, have induction, and have a cesarean. Risks of the composite (16.1% vs 5.4%; adjusted odds ratio, 3.2; 95% confidence interval, 2.1–4.8 from logistic regression) were more frequent with elective early-term birth. Propensity scores matching confirmed the increased primary composite in elective early-term births: adjusted odds ratios, 4.3 (95% confidence interval, 1.8–10.5) for 1:1 and 3.5 (95% confidence interval, 1.8–6.5) for 1:2 matching. Among components of the primary outcome, CPAP use and hyperbilirubinemia requiring phototherapy were significantly increased. Transient tachypnea of the newborn, neonatal intensive care unit admission, and prolonged neonatal intensive care unit stay (>2 days) were also increased with early-term birth. Conclusion Even with confirmed pulmonary maturity, early-term birth in the absence of medical or obstetric indications is associated with worse neonatal respiratory and hepatic outcomes compared with full-term birth, suggesting relative immaturity of these organ systems in early-term births.

Although preterm birth37 weeks' gestation is the leading cause of neonatal morbidity and mortality in the United States, the majority of data regarding preterm neonatal outcomes come from older studies, and many reports have been limited to only very preterm neonates. Delineation of neonatal outcomes by delivery gestational age is needed to further clarify the continuum of mortality and morbidity frequencies among preterm neonates.We sought to describe the contemporary frequencies of neonatal death, neonatal morbidities, and neonatal length of stay across the spectrum of preterm gestational ages.This was a secondary analysis of an obstetric cohort of 115,502 women and their neonates who were born in 25 hospitals nationwide, 2008 through 2011. All liveborn nonanomalous singleton preterm (23.0-36.9 weeks of gestation) neonates were included in this analysis. The frequency of neonatal death, major neonatal morbidity (intraventricular hemorrhage grade III/IV, seizures, hypoxic-ischemic encephalopathy, necrotizing enterocolitis stage II/III, bronchopulmonary dysplasia, persistent pulmonary hypertension), and minor neonatal morbidity (hypotension requiring treatment, intraventricular hemorrhage grade I/II, necrotizing enterocolitis stage I, respiratory distress syndrome, hyperbilirubinemia requiring treatment) were calculated by delivery gestational age; each neonate was classified once by the worst outcome for which criteria was met.In all, 8334 deliveries met inclusion criteria. There were 119 (1.4%) neonatal deaths. In all, 657 (7.9%) neonates had major morbidity, 3136 (37.6%) had minor morbidity, and 4422 (53.1%) survived without any of the studied morbidities. Deaths declined rapidly with each advancing week of gestation. This decline in death was accompanied by an increase in major neonatal morbidity, which peaked at 54.8% at 25 weeks of gestation. As frequencies of death and major neonatal morbidity fell, minor neonatal morbidity increased, peaking at 81.7% at 31 weeks of gestation. The frequency of all morbidities fell32 weeks. After 25 weeks, neonatal length of hospital stay decreased significantly with each additional completed week of pregnancy; among babies delivered from 26-32 weeks of gestation, each additional week in utero reduced the subsequent length of neonatal hospitalization by a minimum of 8 days. The median postmenstrual age at discharge nadired around 36 weeks' postmenstrual age for babies born at 31-35 weeks of gestation.Our data show that there is a continuum of outcomes, with each additional week of gestation conferring survival benefit while reducing the length of initial hospitalization. These contemporary data can be useful for patient counseling regarding preterm outcomes.

Objective We sought to describe the prevalence of serious maternal complications following early preterm birth by gestational age (GA), delivery route, and type of cesarean incision. Study Design Trained personnel abstracted data from maternal and neonatal charts for all deliveries on randomly selected days representing one third of deliveries across 25 US hospitals over 3 years (n = 115,502). All women delivering nonanomalous singletons between 23-33 weeks' gestation were included. Women were excluded for antepartum stillbirth and highly morbid conditions for which route of delivery would not likely impact morbidity including nonreassuring fetal status, cord prolapse, placenta previa, placenta accreta, placental abruption, and severe and unstable maternal conditions (cardiopulmonary collapse, acute respiratory distress syndrome, seizures). Serious maternal complications were defined as: hemorrhage (blood loss ≥1500 mL, blood transfusion, or hysterectomy for hemorrhage), infection (endometritis, wound dehiscence, or wound infection requiring antibiotics, reopening, or unexpected procedure), intensive care unit admission, or death. Delivery route was categorized as classic cesarean delivery (CCD), low transverse cesarean delivery (LTCD), low vertical cesarean delivery (LVCD), and vaginal delivery. Association of delivery route with complications was estimated using multivariable regression models yielding adjusted relative risks (aRR) controlling for maternal age, race, body mass index, hypertension, diabetes, preterm premature rupture of membranes, preterm labor, GA, and hospital of delivery. Results Of 2659 women who met criteria for inclusion in this analysis, 8.6% of women experienced serious maternal complications. Complications were associated with GA and were highest between 23-27 weeks of gestation. The frequency of complications was associated with delivery route; compared with 3.5% of vaginal delivery, 23.0% of CCD (aRR, 3.54; 95% confidence interval (CI), 2.29–5.48), 12.1% of LTCD (aRR, 2.59; 95% CI, 1.77–3.77), and 10.3% of LVCD (aRR, 2.27; 95% CI, 0.68–7.55) experienced complications. There was no significant difference in complication rates between CCD and LTCD (aRR, 1.37; 95% CI, 0.95–1.97) or between CCD and LVCD (aRR, 1.56; 95% CI, 0.48–5.07). Conclusion The risk of maternal complications after early preterm delivery is substantial, particularly in women who undergo cesarean delivery. Obstetricians need to be prepared to manage potential hemorrhage, infection, and intensive care unit admission for early preterm births requiring cesarean delivery.

[Naphthyl-3H] WIN 55212-2 was prepared at high specific activity by the catalytic tritiation of dibromo precursor 3. Product 4 was characterized by chromatography as well as tritium NMR and proven to be a useful radioligand. Copyright © 2002 John Wiley & Sons, Ltd.

Objective We sought to evaluate whether the presence of condition-specific obstetric protocols within a hospital was associated with better maternal and neonatal outcomes. Study Design This was a cohort study of a random sample of deliveries performed at 25 hospitals over 3 years. Condition-specific protocols were collected from all hospitals and categorized independently by 2 authors. Data on maternal and neonatal outcomes, as well as data necessary for risk adjustment were collected. Risk-adjusted outcomes were compared according to whether the patient delivered in a hospital with condition-specific obstetric protocols at the time of delivery. Results Hemorrhage-specific protocols were not associated with a lower rate of postpartum hemorrhage or with fewer cases of estimated blood loss >1000 mL. Similarly, in the presence of a shoulder dystocia protocol, there were no differences in the frequency of shoulder dystocia or number of shoulder dystocia maneuvers used. Conversely, preeclampsia-specific protocols were associated with fewer intensive care unit admissions (odds ratio, 0.28; 95% confidence interval, 0.18–0.44) and fewer cases of severe maternal hypertension (odds ratio, 0.86; 95% confidence interval, 0.77–0.96). Conclusion The presence of condition-specific obstetric protocols was not consistently shown to be associated with improved risk-adjusted outcomes. Our study would suggest that the presence or absence of a protocol does not matter and regulations to require protocols are not fruitful.

The tritiation of the nightshade alkaloids dihydrocapsaicin, atropine and nicotine is described.

We examine a sample of 5896 stocks listed on Nasdaq between 1974 and 1988 to see whether the price per share has significant statistical power in forecasting subsequent returns and attrition rates. Consistent with anecdotal evidence, we document a higher mortality rate for lower-priced stocks than for higher-priced issues. Surprisingly, mortality is not related to market capitalization. Our results also hold for subsamples partitioned by industry and issue year. On average, investors are not adequately compensated for this additional mortality risk, earning lower risk-adjusted rates of return on portfolios of lower-priced shares than on portfolios of higher-priced shares.

Dopamine receptor ligands N-0923 (1) and (+/-)-threo-methylphenidate (4) have been labeled with tritium at high specific activity, for becoming useful tools to study the dopamine receptor family.

Methods are presented to tritiate the side chain of dopamine.

This paper studies expectations of capital appreciation in the housing market. We show that expectations impounded in the rent/price ratio at the beginning of the decade successfully predict appreciation rates, but only if we first control for cross-sectional differences in the quality of rental versus owner-occupied housing. We also demonstrate that observed rent/price ratios contain a disequilibrium component that also has power to forecast subsequent appreciation rates. Finally, we provide evidence consistent with euphoria: participants in housing markets appear to overreact to income growth.

Serotonergic agonists buspirone 1 and (+/−)-DOB 4 have been labeled with tritium at high specific activity and have emerged as valuable tools to study the serotonin receptor family.

Background Cesarean delivery in the second stage of labor is common, whereas the frequency of operative vaginal delivery has been declining. However, data comparing outcomes for attempted operative vaginal delivery vs cesarean in the second stage are scant. Previous studies that examine operative vaginal delivery have compared it to a baseline risk of complications from a spontaneous vaginal delivery and cesarean delivery. However, when a woman has a need for intervention in the second stage, spontaneous vaginal delivery is not an option she or the provider can choose. Thus, the appropriate clinical comparison is cesarean vs operative vaginal delivery. Objective Our objective was to compare outcomes by the first attempted operative delivery (vacuum, forceps vs cesarean delivery) in patients needing second-stage assistance at a fetal station of +2 or below. Study Design We conducted secondary analysis of an observational obstetric cohort in 25 academically affiliated US hospitals over a 3-year period. A subset of ≥37 weeks, nonanomalous, vertex, singletons, with no prior vaginal delivery who reached a station of +2 or below and underwent an attempt at an operative delivery were included. Indications included for operative delivery were: failure to descend, nonreassuring fetal status, labor dystocia, or maternal exhaustion. The primary outcomes included a composite neonatal outcome (death, fracture, length of stay ≥3 days beyond mother's, low Apgar, subgaleal hemorrhage, ventilator support, hypoxic encephalopathy, brachial plexus injury, facial nerve palsy) and individual maternal outcomes (postpartum hemorrhage, third- and fourth-degree tears [severe lacerations], and postpartum infection). Outcomes were examined by the 3 attempted modes of delivery. Odds ratios (OR) were calculated for primary outcomes adjusting for confounders. Final mode of delivery was quantified. Results In all, 2531 women met inclusion criteria. No difference in the neonatal composite outcome was observed between groups. Vacuum attempt was associated with the lowest frequency of maternal complications (postpartum infection 0.2% vs 0.9% forceps vs 5.3% cesarean, postpartum hemorrhage 1.4% vs 2.8% forceps vs 3.8% cesarean), except for severe lacerations (19.1% vs 33.8% forceps vs 0% cesarean). When confounders were taken into account, both forceps (OR, 0.16; 95% confidence interval, 0.05–0.49) and vacuum (OR, 0.04; 95% confidence interval, 0.01–0.17) were associated with a significantly lower odds of postpartum infection. The neonatal composite and postpartum hemorrhage were not significantly different between modes of attempted delivery. Cesarean occurred in 6.4% and 4.4% of attempted vacuum and forceps groups ( P = .04). Conclusion In patients needing second-stage delivery assistance with a station of +2 or below, attempted operative vaginal delivery was associated with a lower frequency of postpartum infection, but higher frequency of severe lacerations.

International audience; OBJECTIVE: To describe CSF biomarker profiles in posterior cortical atrophy (PCA), which induces high-order visual deficits often associated with Alzheimer disease (AD) pathology, and relate these findings to clinical and neuropsychological assessment. METHODS: This prospective observational study included 22 patients with PCA who underwent CSF biomarker analysis of total tau (t-tau), phosphorylated tau on amino acid 181 (p-tau181), and amyloid β (Aβ(42)). At group level, the CSF profiles of patients with PCA were compared to those of patients with typical AD and patients with other dementia (OD). Individually, the clinical presentation of patients with PCA was correlated to their CSF profile to assess the predictability of clinical features for diagnosis of underlying AD pathology. RESULTS: At group level, the PCA biomarker profile was not different from that of the AD group, but very different from that of the OD group (p < 0.001). More than 90% of patients with PCA had CSF profiles consistent with AD. All patients with PCA with either isolated higher-order visual deficit (n = 8) or visual deficit associated with memory impairment (n = 11) had CSF profiles consistent with AD. Only one of the 3 patients with PCA with asymmetric motor signs fulfilled biological CSF criteria for AD. CONCLUSIONS: PCA syndrome is usually associated with CSF biomarkers suggestive of AD, as shown by previous neuropathologic studies. This does not apply in case of motor signs suggesting associated corticobasal syndrome. CSF biomarkers help to discriminate AD from non-AD processes associated with this condition.

The incorporation of a retroreflecting, pseudoconjugating cone as a folding element in a double‐pass unstable resonator of a high‐power carbon dioxide oscillator–amplifier is presented. The concept, when implemented with a truncated cone, has yielded significant improvements in optical energy extraction efficiency, beam quality, and alignment stability. The performance of such a modified clear aperture cone resonator, in comparison with a standard roof prism cavity geometry, is discussed.

Beta-funaltrexamine is a unique irreversible antagonist for the mu-opiate receptor and would be useful as a tritiated radioligand. Starting from high specific activity [15, 16-³H] naltrexone, [15, 16-³H] beta-funaltrexamine was synthesized and characterized by means of a two-step reductive amination-acylation process.

Methods are presented for tritiating the D2 specific dopaminergic antagonist domperidone and D3 specific dopaminergic agonist (+/−)-7-hydroxy DPAT. Techniques to characterize the products of the tritiation are also given.

Phase locking in an extended‐area, multichannel, radial array, carbon dioxide laser has been investigated. Preliminary self‐phase‐locking percentages as high as 62% were achieved with the device. The phase‐locking mechanism was determined to be the mutual optical coupling present within the central region of this geometry. As such, this region acted as a core oscillator to initiate a fundamental optical mode within each individual discharge slot.

A flavonol O -methyltransferase cDNA clone (p F3′OMT ) from Chrysosplenium americanum was expressed in Escherichia coli Top 10 and the recombinant protein was purified to near homogeneity by affinity chromatography on chelation resin and gel filtration on Superose 12 columns. The purified protein was enzymatically active as a 42 kDa monomer and exhibited strict specificity for position 3′ of 3,7,4′-trimethylquercetin. It did not accept the mono- or dimethyl analogs, the parent aglycone quercetin or the phenylpropanoids, caffeic and 5-hydroxyferulic acids as substrates; thus indicating its involvement in the later steps of polymethylated flavonol synthesis in this plant. The K m values of the enzyme for 3,7,4′-trimethylquercetin as substrate and S -adenosyl- l -methionine as co-substrate were 7.2 and 20 μ M, respectively. The enzyme activity was strongly inhibited by both Ni 2+ and ρ -chloromercuribenzoate and was restored by the addition of EDTA or β -mercaptoethanol, respectively. Antibodies raised against the F3′OMT recombinant protein recognized a protein band migrating at the expected molecular mass of the enzyme on SDS-polyacrylamide gels of protein extracts prepared from various sources. This implies a high degree of structural similarity among these enzymes that is also corroborated by their hydropathy profiles.

A 30 kW, continuous wave (CW), Photo-initiated, Impulse-enhanced, Electrically-excited (PIE) CO2 laser is presented. This high power laser system is unique in that it is also capable of modulated optical output over a wide range of frequencies featuring multi-kilowatt peak power with high average power. The primary focus of this paper is documentation of the enhanced performance achievable from this laser when operated under a burst mode excitation technique. Excitation of the system, using a burst mode process, results in a dramatic change in the output characteristics of the laser. Control of burst frequency and duty cycle provides a convenient means to alter the time-varying nature of the output beam. Low burst frequencies result in clearly defined pulse profiles, falling to zero in between pulses. Increasing burst frequency results in a significant offset or quasi-CW time-varying output. At low burst durations, optical output has a triangular profile. Increasing burst duty cycles produce square optical pulse shape profiles. High frequency, large duty cycle operation produces an optical output approaching that observed in CW. The significance of these results are manifest in a major enhancement in deep penetration welding at reduced average laser powers. Welding performance, featuring a 400% increase in penetration as compared to CW welding, has been demonstrated at the same average power level. Reductions in average laser power and plasma suppression gas requirements could translate into major savings in high power laser welding applications utilizing this unique excitation process. Another attractive aspect of burst mode welding is its potential for deep penetration alloying of inexpensive base materials through incorporation of a computer controlled wire-feed/MIG system.A 30 kW, continuous wave (CW), Photo-initiated, Impulse-enhanced, Electrically-excited (PIE) CO2 laser is presented. This high power laser system is unique in that it is also capable of modulated optical output over a wide range of frequencies featuring multi-kilowatt peak power with high average power. The primary focus of this paper is documentation of the enhanced performance achievable from this laser when operated under a burst mode excitation technique. Excitation of the system, using a burst mode process, results in a dramatic change in the output characteristics of the laser. Control of burst frequency and duty cycle provides a convenient means to alter the time-varying nature of the output beam. Low burst frequencies result in clearly defined pulse profiles, falling to zero in between pulses. Increasing burst frequency results in a significant offset or quasi-CW time-varying output. At low burst durations, optical output has a triangular profile. Increasing burst duty cycles produce square optica...

The inhibitory reflex evoked in single motor units in human masseter by lip stimulation was recorded at several joint angles. The pre-stimulus firing frequency of the unit was kept constant. Some modulation of the inhibitory response at different vertical jaw positions (i.e., temporomandibular joint angle) was observed in most masseter units, with the majority of the modulated units being inhibited less when the teeth were closer together.

The application of a burst-mode pulsed discharge technique to a large-volume, multikilowatt, PIE (photo-initiated, impulse-enhanced, electrically excited) carbon dioxide laser is described. A factor of two enhancement in average output power, up to the 10 kW level, was obtained using a burst duration of 1.2 ms and a repetition rate of 500 burst/s. The small signal-gain increased to essentially double that of the normal continuous-wave value. Gain profile information, together with details of the laser's power performance, as a function of various discharge parameters, is illustrated. These data clearly document the versatility of this unique and cost-effective burst-mode laser excitation process. >

This study of the Black bear (Ursus amerícanus) was undertaken to provide basic information related to structural modifications in the renal microvasculature that might provide insight into the drastic alteration in renal urinary output that occurs during winter sleep. Vascular casts, as well as light microscopy and scanning electron microscopy, were used to study the vascular components of the juxtaglomerular complex and related vessels. Histologically, arterial cushions were readily identified at the origin of the afferent arterioles. In the area of the juxtaglomerular complex, the wall of the afferent arteriole appeared to be highly modified. The smooth muscle cells at this site demonstrated a change in morphology and orientation, and the diameter of the arteriole was altered. The pattern of the vascular casts at the origin of the afferent arteriole varied from that portion at the glomerulus, suggesting a modification of the vascular wall near the renal corpuscle. Although the morphology of the renal microvasculature of the Black bear is similar to that of other mammals in some aspects, it is dissimilar to that of other carnivores and of the human kidney in that there are structural modifications of the afferent arteriole that may contribute to a reduction of blood flow to the nephron during winter sleep.

A high-pressure high-repetition-rate pulsed-discharge technique is described. Ultraviolet preionization and voltage switching are integrated using spark-gap switches in a geometry such that they will irradiate the discharge gas. A repetition rate of 4000 pulses per second (pps) has been achieved.

The effects of dieldrin (hexachloro-epoxy-octahydro-dimethanonaphthalene) were studied in acute experiments on cats and rabbits. When injected intravenously or intra-arterially, it caused excitation of the central nervous system, which resulted in increased reflex excitability, convulsions, bradycardia, and some vasodepression. Dieldrin potentiated the effects of acetylcholine on the central nervous system and on the circulatory system as well as on intestinal motility. These latter manifestations were abolished by section of the vagus nerves, indicating a central action. Dieldrin had no effect on salivary secretion produced either by stimulation of the chorda tympani or by injections of acetylcholine in the decentralized submaxillary gland. Thus, although dieldrin has a marked parasympathomimetic action, this effect is exerted through stimulation of central mechanisms and not peripherally.

Introduction Chemical agents have been used in the past to study the sensitivity to convulsions of animals with various cerebral ablations. Drake, Seguin, and Stavraky 1 have shown that after unilateral frontal lobectomy cats become more responsive to pentylenetetrazol and to other convulsant agents, and Seguin and Stavraky 2 have found that these animals are also more susceptible to the action of depressant agents, such as pentobarbital sodium and phenobarbital sodium. In the light of these findings and the paucity of literature pertaining to the sensitivity of frontal lobectomized animals to electroshocking procedures, the present study was undertaken. The study was divided into two parts: one dealing with electroshock and the other with electronarcosis. The convulsability thresholds and the picture of convulsive manifestations in control and operative animals were compared in the case of electroshock, and the narcotic levels and behavior of the two groups of animals were studied in

In 52 cats in which the left frontal lobe (including the motor cortex) or the whole cerebral hemisphere had been removed 3 months to 2 years previously, sodium pentobarbital (i.v., 1.0–2.0 mg./kg.) caused weakness and in-co-ordination in the decentralized limbs. Larger quantities of pentobarbital (3.0–8.0 mg./kg.) made the animals unable to stand ('standing test') for 13.0 ± 1.8 minutes while 25 control cats exhibited this effect for 5.6 ± 1.5 minutes. Using the 'standing test' as a criterion the median effective dose of pentobarbital was found to be 1.7 mg./kg. for the operated group and 3.7 mg./kg. for the controls, the difference being statistically significant. Sodium phenobarbital had similar effects.Injected (i.m.) 1 hour before pentylenetetrazol (10 mg./kg.) in 21 operated and 19 control cats, pentobarbital (1.0–6.0 mg./kg.) reduced the incidence and severity of convulsions in the operated cats to a greater extent than in the controls, as judged by a conversion of the clonic–tonic–clonic fits into purely clonic seizures.In 23 spinal cats in which the spinal cord was semisected 9 to 39 days previously, the excitability of the motoneurones was tested by means of intra-aortal injections of acetylcholine (ACh, 0.03–3 mg./kg.). Small quantities of pentobarbital occasionally augmented the responses to ACh whereas larger quantities of pentobarbital (0.3–11.0 mg./kg.) or phenobarbital (0.7–6.0 mg./kg.) had a depressant effect, both actions being more marked on the semisected side. The significance of these findings is discussed.

The effects of removal of one motor cortex, a frontal lobe, or a complete cerebral hemisphere on the action of various convulsant agents were studied in chronic cats and in spinal preparations. In both sets of experiments, previously decentralized neurons responded to smaller quantities of convulsant drugs than did the intact ones, and pentylenetetrazol, camphor, and picrotoxin, as well as strychnine and acetylcholine, evoked greater and more prolonged responses from these neurons when sufficient time was allowed for sensitization due to partial isolation to take place (in the majority of experiments two to eight months).This was ascertained in myographic recordings and in studies of the electrical activity of the anterior horn cells in high spinal cats and white rats, as well as in photographic and statistical analyses of convulsions induced in chronic animals. The latter study revealed that the convulsions were asymmetrical in the operated cats, the muscular contractions being exaggerated and prolonged contralaterally to the cerebral ablation. The median convulsant dose (CD50) of pentylenetetrazol for the control cats was 7.8 mgm./kgm. (95% confidence limits 7.4–8.1) while that for the operated group was 6.8 mgm./kgm. (95% confidence limits 6.3–7.2). The latent period following the injection of pentylenetetrazol was significantly shorter for the operated group than for the control one, and the convulsions lasted longer in the operated cats than in intact animals. The longer duration of convulsions in the operated group depended on a significantly longer tonic and terminal clonic phase of the convulsion. Two patterns of convulsions could be elicited—a clonic and a more severe clonic–tonic–clonic (CTC) one. In the control group clonic convulsions were more frequent at low dosages of pentylenetetrazol while CTC convulsions pre-dominated at high dosages. In the operated group CTC convulsions were prevalent throughout the range of doses used and occurred in a greater percentage of animals than in the control group. Chemically induced convulsions play a prominent part in the study of epilepsy and in the treatment of some mental derangements, and it is felt that this investigation may contribute to the understanding of the mechanism of action of convulsant agents on the nervous system in which abnormal conditions prevail.

Hydroquinidine concentrations were measured simultaneously in the plasma and in right atrial and ventricular biopsy samples of four dogs in the steady state after eight days of oral sustained release hydroquinidine administration. The right ventricular concentrations were greater than the plasma concentrations in all samples (ratio 5.02(2.2)). In necropsy samples the ventricular concentrations were higher than the atrial concentrations, (ratio 1.54(0.36); p less than 0.01) and than the concentration in the sinus node region (7.72(1.85) ng.g-1 vs 4.21(2.6) ng.g-1). This study shows that intramyocardial pharmacokinetic measurements are possible and may help towards a better understanding of antiarrhythmic agents, particularly those with cumulative myocardial effect.

Morphological features of the coronary microvasculature were examined in ten Black bears (Ursus americanus). Tissue samples were collected for scanning electron microscopy from five animals, and vascular casts of the coronary vessels were prepared from five. Each portion of the microvasculature examined had specific morphological characteristics which may contribute to the control of blood flow. All indications from the present study suggest that the structure of the coronary microvasculature in the Black bear is similar to that of mammalian species previously examined.

In this paper, we have compared mastication and the oral movements of speech. We have tried to show how some data from recent experiments on mastication could be equally important for the understanding of speech motor control.

The effects of cutaneous stimulation on tonic and phasic responses to stretch were studied in the triceps surae complex of unanesthetized, decerebrate cats. The tonic response was produced by a maintained stretch of the muscle group to 80–85% of its maximum length. Stretch was applied directly to the isolated tendon at the calcaneus. Phasic responses were elicited by a ramp stretch of 1.0 to 2.0 mm superimposed on the maintained stretch. Mild, brief, electrical or mechanical stimulation of the plantar cushion caused a sequence of inhibitory and excitatory changes in the tonic EMG activity in the soleus muscle. Mild stimuli, applied 0.01 to 5 ms before the start of ramp stretch, decreased the size of the phasic response to stretch and converted it into a biphasic response. It is suggested that stimulation of cutaneous mechanoreceptors may be responsible for variations in the initial burst of EMG activity seen in the agonist muscle during the response to perturbation or fast voluntary movement in animals and man.

1. The activity of cutaneous mechanoreceptors was recorded extracellularly in the mandibular division of the Gasserian ganglion of hemidecerebrate anesthetized rabbits. Fifty-four hair follicle afferents and 80 skin mechanoreceptor afferents were functionally identified. Their receptive-field characteristics were described and their activity patterns were recorded while the jaw was displaced by hand in the vertical, horizontal, and anterior-posterior directions, and during masticatory movements. 2. All hair follicle afferents were classified as rapidly adapting, whereas skin afferents could be divided into two categories: rapidly adapting and slowly adapting. Rapidly and slowly adapting receptors were found in all regions of the mandibular skin. Only one hair follicle afferent and four skin afferents fired spontaneously with the jaw at rest. 3. Fifty-eight percent (29/50) of the hair follicle afferents were activated by imposed displacement of the jaw and all of these tested also discharged during chewing. They were sensitive to movement in all three axes and their firing frequency was linearly related to the velocity, regardless of direction. 4. Only 10% (8/80) of the skin afferents were activated by imposed displacement of the jaw if their receptive fields were not directly contacted. Firing frequency was not well related to either the amplitude or velocity of movement. During chewing, the discharge frequency was variable but, in general, firing was restricted to the jaw-closing phase. Most skin afferents that were active during jaw movement had receptive fields close to the corner of the mouth. 5. The results are discussed within the context of a possible involvement of cutaneous afferents in kinesthesia and in the control of jaw movements. Hair afferents could make specific contributions to the appreciation of movement because their discharge pattern was clearly related to one of its parameters. The lack of activity of most skin afferents, as well as the absence of a strong correlation between the firing frequency of those that were active and the movement parameters, suggest that they do not make specific contributions to the awareness of movement. 6. Hair and skin afferents may also make different contributions to the control of ongoing movements. It is suggested that skin afferent activity during jaw closure may elicit a reflex reduction in the velocity or duration of this phase. Some evidence from other studies suggests that hair afferent activity may indirectly influence movement via effects on elevator fusimotor neurons.

1. This investigation had two main objectives: first to determine whether or not motor activity could be elicited by localized intracortical stimulation in somatosensory area II of the cat, and secondly to identify, by antidromic stimulation, neurones which projected to subcortical structures and to study their afferent input. 2. Although arm movements could be elicited in most cats by intracortical train stimulation with tungsten micro-electrodes, the lowest motor thresholds were much higher than the lowest thresholds for the primary motor area under similar experimental conditions. Facial responses were evoked at lower stimulus thresholds, but the threshold decreased steadily as successive stimulation tracks approached the coronal face area. Previously observed responses to prolonged surface stimulation could have been caused by intracortical spread of excitation or by escape of stimulus to the primary area, especially the face area. 3. Neurones with corticofugal axons projecting to bulbar and spinal levels were first identified by their antidromic response to stimulation of the cerebral peduncle. Each was further tested by stimulation of the cervical corticospinal tract, and the dorsal column nuclei. Their receptive fields were then recorded. 4. It was possible to classify the neurones into four main categories: (i) non-descending neurones: neurones not activated antidromically by any of the subcortical stimulating electrodes. The majority of these neurones had very small (lemniscal type) receptive fields, (ii) corticobulbar neurones: these were invaded antidromically by stimulation of the peduncle but not by spinal or dorsal column nuclei stimulation. They had `stocking-like' or larger receptive fields; (iii) cortico-spinal neurones: neurones driven antidromically by stimulation of corticospinal fibres. Characteristically, these neurones had large confluent fields, often bilateral. Very few had receptive fields of the lemniscal type; (iv) neurones invaded by dorsal column nuclei stimulation: the number of such units was extremely low and their receptive fields were large or `stocking-like'. 5. The results indicate that somatosensory area II in the cat does not exert an independent motor control of spinal neurones, and it is thought that corticofugal neurones of SII are involved in the control of somatosensory transmission rather than having a direct motor function.

Following section of the corpus callosum, white rats become more sensitive than sham-operated animals to the action of pentylenetetrazol. This is shown by an increase in the duration of convulsions and incidence of clonic, tonic, and repeated convulsions which are significantly greater in corpus callotomized rats than in control animals. In addition, in the corpus callotomized rats the effects of pentylenetetrazol appear more quickly than they do in the controls.It was shown in the present investigation that exposure of the corpus callotomized and sham-operated rats to extremes of environmental temperature for 1-week periods resulted in an increased excitability and convulsibility of control animals. This effect was obtained following exposure to either low (4 °C) or tropical (34 °C) temperatures. Under similar conditions, corpus callotomized animals showed little change in convulsibility or excitability, as defined in the present study, since they had apparently reached almost a maximal state of sensitivity due to the preceding section of the commissural fibers and partial denervation of the cerebral cortical neurones; however, these animals did have a greater number of repeated convulsions when exposed to the tropical temperature, a result which may be interpreted as being due to some further increase in their sensitivity to pentylenetetrazol.

Introduction It was shown previously that cats and white rats which had undergone removal of one cerebral hemisphere or of a frontal lobe, including the motor cortex, were more susceptible to pentylenetetrazol convulsions than unoperated animals.1-3The question remained as to which regions of the central nervous system were sensitized by these operations. An answer to this question was sought in the present investigation by testing the effects of pentylenetetrazol on Sprague-Dawley rats in which partial denervation was confined to cerebral cortical neurones. This was accomplished by sectioning the corpus callosum. Experimental Procedure Male Sprague-Dawley rats were divided randomly into 3 groups. In one group the corpus callosum was sectioned aseptically under pentobarbital (Nembutal) anesthesia, one control group was left intact, and in another a sham trepanation was performed under identical conditions with the corpus callotomy. One to 5 months after the operation, the CD50(median convulsant dose)

PubMed: 29599078, 2-s2.0-85044540918, Background: The 69th World Health Assembly approved the Global Health Sector Strategy to eliminate viral hepatitis by 2030. Although no virological cure exists for hepatitis B virus (HBV) infection, existing therapies to control viral replication and prophylaxis to minimise mother-to-child transmission make elimination of HBV feasible. We aimed to estimate the national, regional, and global prevalence of HBsAg in the general population and in the population aged 5 years in 2016, as well as coverage of prophylaxis, diagnosis, and treatment. Methods: In this modelling study, we used a Delphi process that included a literature review in PubMed and Embase, followed by interviews with experts, to quantify the historical epidemiology of HBV infection. We then used a dynamic HBV transmission and progression model to estimate the country-level and regional-level prevalence of HBsAg in 2016 and the effect of prophylaxis and treatment on disease burden. Findings: We developed models for 120 countries, 78 of which were populated with data approved by experts. Using these models, we estimated that the global prevalence of HBsAg in 2016 was 3·9% (95% uncertainty interval [UI] 3·4–4·6), corresponding to 291 992 000 (251 513 000–341 114 000) infections. Of these infections, around 29 million (10%) were diagnosed, and only 4·8 million (5%) of 94 million individuals eligible for treatment actually received antiviral therapy. Around 1·8 (1·6–2·2) million infections were in children aged 5 years, with a prevalence of 1·4% (1·2–1·6). We estimated that 87% of infants had received the three-dose HBV vaccination in the first year of life, 46% had received timely birth-dose vaccination, and 13% had received hepatitis B immunoglobulin along with the full vaccination regimen. Less than 1% of mothers with a high viral load had received antiviral therapy to reduce mother-to-child transmission. Interpretation: Our estimate of HBV prevalence in 2016 differs from previous studies, potentially because we took into account the effect of infant prophylaxis and early childhood vaccination, as well as changing prevalence over time. Although some regions are well on their way to meeting prophylaxis and prevalence targets, all regions must substantially scale-up access to diagnosis and treatment to meet the global targets. Funding: John C Martin Foundation. © 2018 Elsevier Ltd, H28-kansei-ippan-001 National Academy of Sciences, NAS Novartis Roche World Health Organization, WHO Gilead Sciences Alnylam Pharmaceuticals AbbVie Meso Scale Diagnostics, MSD British Microcirculation Society, BMS Japan Society for the Promotion of Science, JSPS: 17H03589 Ministry of Health, Labour and Welfare, MHLW Vetenskapsrådet, VR Siemens Universiteit Antwerpen OLL-683801, DR-S, IGa, SB, SMB, CE, KM, HMN, KP, KR-S, SR, JDS, and HR report grants from John C Martin Foundation, during the conduct of the study, and grants from Gilead Sciences, AbbVie, WHO, National Academy of Sciences, Intercept Pharmaceuticals, and Boehringer Ingelheim, outside the submitted work. MHN reports grants and personal fees from Bristol-Myers Squibb (BMS), Gilead Sciences, and Janssen, and personal fees from Novartis, Anylam, and Dynavax, outside the submitted work. PVD acts as chief and principal investigator for vaccine trials done on behalf of the University of Antwerp, Belgium, for which the University obtains research grants from vaccine manufacturers; speaker's fees for presentations on vaccines are paid directly to an educational fund held by the University of Antwerp, and PVD receives no personal remuneration for this work. ACA reports personal fees from Mylan Pharmaceuticals, outside the submitted work. JEA reports fees paid to his hospital for participation on the advisory boards of Gilead Sciences, ViiV Healthcare, BMS, Janssen, and AbbVie, and grants from BMS, Merck Sharp & Dohme (MSD), AbbVie, and ViiV Healthcare, outside the submitted work. TB reports grants, personal fees, and non-financial support from AbbVie and Gilead Sciences; grants and personal fees from BMS, Janssen, Roche, MSD, and Sequana Medical; and personal fees from Bayer, Vertex, Tibotec, Intercept, Sirtex, and Alexion, outside the submitted work. PB reports grants and personal fees from AbbVie, Gilead Sciences, and MSD, outside the submitted work. MBr reports personal fees from BMS, Gilead Sciences, and Janssen, and grants from BMS, outside the submitted work. HLYC reports personal fees from Gilead Sciences, BMS, AbbVie, Roche, MedImmune, and Intellia, outside the submitted work. PBC reports grants from AbbVie, Gilead Sciences, and MSD, outside the submitted work. VC reports personal fees from AbbVie, BMS, Gilead Sciences, and MSD, and grants from BMS, outside the submitted work. MCor reports personal fees from AbbVie, BMS, Boehringer Ingelheim, Biogen Idec, Falk Foundation, Gilead Sciences, Janssen, MSD, Roche Diagnostics, Roche Pharma, and Siemens, outside the submitted work. SD and PJ report personal fees and non-financial support from AbbVie and Gilead Sciences, and personal fees from MSD, outside the submitted work. MHE-S is an advisory board member for Perspectum Diagnostics, and reports grants and non-financial support from Gilead Sciences, and non-financial support from AbbVie and Quadri Pharma, outside the submitted work. RF reports grants, personal fees, and non-financial support from Roche and Gilead Sciences, and personal fees and non-financial support from BMS, outside the submitted work. GBG reports grants and personal fees from Gilead Sciences, outside the submitted work. JG-S reports grants and personal fees from Gilead Sciences, and personal fees from MSD, Abbvie, Janssen, and BMS, outside the submitted work. JGer reports grants and personal fees from AbbVie, Gilead Sciences, Janssen, MSD, BMS, and ViiV Healthcare, outside the submitted work. RG reports grants from New South Wales Ministry of Health and provided project advice regarding viral hepatitis treatment to Gilead Sciences, outside the submitted work. AHa reports unrestricted grants from AbbVie, MSD, Gilead Sciences, BMS, and Novartis, and non-financial support from Gilead Sciences, outside the submitted work; he was also on advisory boards for AbbVie, Gilead Sciences, and BMS. CH reports personal fees from AbbVie, BMS, Gilead Sciences, Janssen, and MSD, outside the submitted work. JJ reports personal fees and non-financial support from Gilead Sciences and AbbVie, and personal fees from Roche and BMS, outside the submitted work. MK reports grants from Roche, Siemens, Hologic, and Boerhinger Ingleheim, outside the submitted work. JVL reports grants and personal fees from Gilead Sciences and personal fees from Cepheid, outside the submitted work. MMan reports personal fees from Roche, BMS, GlaxoSmithKline, Aevi Genomic Medicine, ENYO Pharma, and CureVac, and grants and personal fees from Gilead Sciences and Novartis, outside the submitted work. SMau reports personal fees and non-financial support from Gilead Sciences and BMS, outside the submitted work. CM reports grants and personal fees from AbbVie, Gilead Sciences, and BMS; personal fees from MSD; and grants from Roche, outside the submitted work. BM reports grants and personal fees from Gilead Sciences and personal fees from AbbVie, MSD, BMS, Bayer, Intercept, and Sigma-Tau, during the conduct of the study. FN reports personal fees and non-financial support from Gilead Sciences, during the conduct of the study. AR reports grants and personal fees from AbbVie, Gilead, and MSD, and personal fees form BMS, Celgene, Janssen, Intercept, and Lupin, outside the submitted work. HWR reports grants and personal fees from AbbVie, BMS, Boehringer Ingelheim, ENYO Pharma, Gilead Sciences, Janssen, MSD, PRA Health Sciences, Regulus, and Roche; personal fees from Alnylam and R-Pharm; and grants from Replicor, outside the submitted work. LRR reports grants from the Center for Clinical and Translational Science and the Swedish Research Council (Ghana), during the conduct of the study. LRR also reports grants from Gilead Sciences, BTG, Ariad, and Wako, outside the submitted work, and was a consultant and advisory board member for Wako, Medscape, Axis, OncLive, Bayer, Tavec, and Grail. SDR has served as an advisory board member and speaker for Gilead Sciences, AbbVie, and MSD. OS has served as a consultant and on advisory boards for MSD; received research grants from AbbVie, BMS, MSD, Boehringer Ingelheim, R-Pharm, and Hepatera; and served as a speaker for Abbott, AbbVie, BMS, Gilead Sciences, Janssen, MSD, and R-Pharm. JFS-A reports personal fees from AbbVie and grants from Gilead Sciences and Janssen, outside the submitted work. CSa reports personal fees from Gilead Sciences and BMS, outside the submitted work. PS reports grants and personal fees from Gilead Sciences, AbbVie, and BMS, and personal fees from Intercept, outside the submitted work. CSt has consulted with and served on advisory boards for Gilead Sciences, AbbVie, and MSD. VSy reports grants and personal fees from Gilead Sciences, personal fees and non-financial support from AbbVie, and personal fees from Janssen, outside the submitted work. KT reports grants and personal fees from AbbVie, Gilead Sciences, and BMS; personal fees from MSD and Alfa Wasserman; and grants from Janssen, outside the submitted work. AJvdM reports grants and personal fees from Gilead Sciences and personal fees from AbbVie, outside the submitted work. IW reports personal fees from AbbVie, Gilead Sciences, Janssen, Marcyrl, Mylan, Onxio, and Pharco, outside the submitted work. NW reports personal fees paid to her department from AbbVie, BMS, Gilead Sciences, and MSD, outside the submitted work. VWW reports personal fees from Gilead Sciences, BMS, and MSD, outside the submitted work. M-FY was a speaker or advisory board member for AbbVie, BMS, Gilead Sciences, Roche, GlaxoSmithKline, Fujirebio, Biocartis, and MSD, outside the submitted work. SZ reports consultancy and lecture fees from AbbVie, Gilead Sciences, and MSD, and consultancy fees from Intercept, outside the submitted work. All other authors declare no competing interests., This study was funded by the John C Martin Foundation through the Polaris Observatory. We thank the Research on Hepatitis group (H28-kansei-ippan-001 and H25-kanen-ippan-010; led by JT), funded by the Ministry of Health, Labour and Welfare of Japan, for their provision of country-level data for Japan, and Örebro County Council for providing ALF grants (OLL-683801) to A-SD, which allowed collection of country-level data for Sweden.