Effect of functional excipients on the dissolution and membrane permeation of furosemide formulated into multiple-unit pellet system (MUPS) tablets.

The effect of functional excipients (i.e. chitosan, sodium lauryl sulphate, NaHCO3, and CaCO3) formulated in multiple-unit pellet system (MUPS) tablets has been investigated on the dissolution and permeability of furosemide, a BCS class IV compound. Spherical beads were produced and compressed into MUPS tablets. MUPS tablet formulations were evaluated for hardness, disintegration, mass variation, friability, and dissolution (pH 1.2, pH 4.6, and pH 7.4). Ex vivo permeability studies were conducted across excised pig tissues (pyloric antrum and duodenal region) on selected experimental MUPS tablet formulations. Histological analysis was conducted on the tissues after exposure to selected experimental MUPS tablet formulations. Dissolution results in the 0.1 M HCl (pH 1.2) showed the highest effect of the excipients on furosemide release. Dissolution parameters showed increased dissolution of furosemide for the MUPS tablet formulations containing functional excipients: a 4.5-10-fold increase in the AUC values, the %max showed a 60-70% increase and up to a 19-fold increase in DRi was seen. Permeability results revealed a 2.5-fold higher cumulative percentage transport for selected formulations. The results proved that functional excipients incorporated into beads, compressed into MUPS tablet formulations increased furosemide release as well as permeation across excised intestinal tissues.

Fertility awareness and parenting intentions among Mexican undergraduate and graduate university students.

An online, cross-sectional survey was carried out between November 2017 and January 2018 to assess fertility awareness among students attending the National Autonomous University of Mexico (UNAM) in Mexico City. A total of 371 students participated in the survey (n = 228 females, 143 males). 75% of females and 74% of males believed a woman's fertility begins to decline markedly after age 40. Over 75% of all participants overestimated the probability of couples having a live birth after undergoing one cycle of IVF. With regard to parenting intentions, only 48% of females wished to have children compared to 59% of males (p = 0.037) and men were more likely to have their first child at age 30 or later (71% men vs 55% women). In the event of infertility, participants had a higher preference not to have children or to pursue adoption rather than use in vitro fertilisation (IVF). In summary, university students in Mexico City demonstrated low levels of fertility awareness and a smaller proportion indicated a wish to have children than has been reported by young people elsewhere in the world.

Impact of Magnetic Field Configuration on Heat Transport in Stellarators and Heliotrons.

We assess the magnetic field configuration in modern fusion devices by comparing experiments with the same heating power, between a stellarator and a heliotron. The key role of turbulence is evident in the optimized stellarator, while neoclassical processes largely determine the transport in the heliotron device. Gyrokinetic simulations elucidate the underlying mechanisms promoting stronger ion scale turbulence in the stellarator. Similar plasma performances in these experiments suggests that neoclassical and turbulent transport should both be optimized in next step reactor designs.

Sensitivity improvement of infrared imaging video bolometer for divertor plasma measurement.

The sensitivity of an infrared imaging video bolometer (IRVB) was improved for the measurement of relatively low energy plasma radiation from the viewpoint of the metal foil absorber material. The photon energy of the radiation was considered up to 1 keV for the divertor plasma measurement. The thickness of the foil absorber was evaluated not only for conventional heavy elements, e.g., platinum, but also for light elements by the relation between the photon energy and attenuation length and by mechanical strength. A heat-transfer calculation using ANSYS suggested that light elements with practical foil thickness provide a higher temperature rise of the foil absorber compared with heavier elements with practical foil thickness. The maximum of the temperature rise was evaluated using He-Ne laser irradiation onto absorber samples. The material dependence of the temperature rise has a similar tendency between calculations and experiments. Experimentally, the sensitivity of the IRVB improved from 280 to 110 µW/cm2 using titanium with 1 µm thickness compared with conventional platinum with 2.5 µm thickness. Consequently, the signal-to-noise ratio of the IRVB could be improved from 2.8 to 9.1.

Development of a weighted sum estimate of the total radiated power from large helical device plasma.

Diagnosing the amount of radiated power is an important research goal for fusion devices. This research aims at better understanding and diagnosing the radiated power from the Large Helical Device (LHD). The current radiated power estimate in the LHD is based on one wide-angle resistive bolometer. Because the estimate stems from one bolometer location toroidally and has a wide-angle poloidal view, this estimate does not take into account toroidal and poloidal radiation asymmetries that are observed in the LHD in discharges with gas puffing. This research develops a method based on the EMC3-Eirene model to calculate the set of coefficients for a weighted-sum method of estimating the radiated power. This study calculates these coefficients by using a least-squares method to solve for a coefficient set, using a variety of simulated cases generated by the EMC3-Eirene model, combined with corresponding geometric radiated power density considerations. If this set of coefficients is multiplied by the detector signal of each bolometer and summed up, this gives a total radiated power estimate. This new estimate takes into account toroidal and poloidal asymmetries by using the bolometer channels viewing different toroidal and poloidal locations, thereby reducing the estimation error and providing information about toroidal asymmetries.

Estimating the diagnostic accuracy of the ankle-brachial pressure index for detecting peripheral arterial disease in people with diabetes: A systematic review and meta-analysis.

AIM: To systematically evaluate research investigating the accuracy of the ankle-brachial index (ABI) for diagnosing peripheral artery disease (PAD) in people with diabetes, as the accuracy is thought to be reduced in this cohort. METHODS: A database search of EBSCO Megafile Premier, Embase and The Cochrane Library was conducted to 28 February 2019. Prospective and retrospective investigations of the diagnostic accuracy of the ABI for PAD in people with diabetes using an imaging reference standard were eligible. Sensitivity and specify of the ABI and bivariate meta-analysis against reference tests, or a standard summary receiver operating curve analysis (SROC) was performed. RESULTS: Thirty-three studies met the inclusion criteria. ABI was compared with angiography in 12 studies and with colour duplex ultrasound (CDUS) in 21 studies. A SROC analysis of studies using angiography as the reference standard found a diagnostic odds ratio (DOR) of 9.06 [95% confidence interval (CI) 3.61 to 22.69], and area under the curve (AUC) of 0.76 (95% CI 0.66 to 0.86). Bivariate analysis of studies using CDUS demonstrated mean sensitivity of 0.60 (95% CI 0.48 to 0.71; P = 0.097) and mean specificity of 0.87 (95% CI 0.78 to 0.92; P < 0.001) with a DOR of 9.76 (95% CI 5.24 to 18.20; P < 0.0001) and AUC 0.72. CONCLUSIONS: These results suggest the ABI has a high specificity but lower sensitivity in detecting imaging diagnosed PAD in people with diabetes. The low probability of the testing being able to rule diagnosis in or out suggest that the ABI has limited effectiveness for early detection of PAD in this cohort.

Top predators induce habitat shifts in prey within marine protected areas.

Emerging conservation efforts for the world's large predators may, if successful, restore natural predator-prey interactions. Marine reserves, where large predators tend to be relatively common, offer an experimental manipulation to investigate interactions between large-bodied marine predators and their prey. We hypothesized that southern stingrays-large, long-lived and highly interactive mesopredators-would invest in anti-predator behavior in marine reserves where predatory large sharks, the primary predator of stingrays, are more abundant. Specifically, we predicted southern stingrays in marine reserves would reduce the use of deep forereef habitats in the favor of shallow flats where the risk of shark encounters is lower. Baited remote underwater video was used to survey stingrays and reef sharks in flats and forereef habitats of two reserves and two fished sites in Belize. The interaction between "protection status" and "habitat" was the most important factor determining stingray presence. As predicted, southern stingrays spent more time interacting with baited remote underwater videos in the safer flats habitats, were more likely to have predator-inflicted damage inside reserves, and were less abundant in marine reserves but only in the forereef habitat. These results are consistent with a predation-sensitive habitat shift rather than southern stingray populations being reduced by direct predation from reef sharks. Our study provides evidence that roving predators can induce pronounced habitat shifts in prey that rely on crypsis and refuging, rather than active escape, in high-visibility, heterogeneous marine habitats. Given documented impacts of stingrays on benthic communities it is possible restoration of reef shark populations with reserves could induce reef ecosystem changes through behavior-mediated trophic cascades.

Initiating patient discussions about oocyte cryopreservation: Attitudes of obstetrics and gynaecology resident physicians.

This study examined the attitudes of obstetrics and gynaecology (OB/GYN) resident physicians to initiating patient discussions regarding medical and elective oocyte cryopreservation (OC). The study used a cross-sectional online survey of OB/GYN medical residents in the USA, sampled from residency programmes approved by the American Council for Graduate Medical Education. In total, 208 medical residents, distributed evenly between postgraduate years 1-4, participated in the study. Residents' fertility knowledge and attitudes to initiating discussions about OC were gathered. Forty percent (n = 83) believed that OB/GYN residents should initiate discussions about OC with patients (initiators), while 60% (n = 125) did not (non-initiators). Initiators were less likely to overestimate the age at which a woman's fertility begins to decline, and were more likely to believe that discussions about OC and age-related fertility decline should take place during a well-woman annual examination. Initiators and non-initiators did not differ in their attitudes towards discussing OC with patients undergoing cancer treatments; however, initiators were significantly more likely to discuss elective OC with patients who were currently unpartnered or who wished to delay childbearing to pursue a career. Given the increasing age of childbearing among women, and the fact that women prefer to receive reproductive information from their healthcare providers, it is critical that such topics are discussed in consultations to assist patients in making more informed reproductive decisions. Further research is needed to assess the existing barriers to these discussions from both physician and patient perspectives.

Improvement of infrared imaging video bolometer for application to deuterium experiment on the large helical device.

An infrared imaging video bolometer was improved for application to a neutron environment in fusion plasma devices, i.e., the Large Helical Device (LHD). In order to calibrate the thermal characteristics of the activated foil absorber inside the plasma vacuum vessel, the remote-controlled in situ calibration system was improved with high-surface-flatness mirrors. Furthermore, the carbon coating method was improved by introducing a vacuum evaporation technique instead of the conventional spray technique to realize the coating on both sides of the absorber with reproducibility and uniformity. The optimal thickness of the coating was also determined. Owing to these coating improvements, the reproducibility of the effective emissivity on both sides especially was improved. Finally, the variation with the neutron irradiation of the thermal characteristics of the foil absorber was investigated. It was found that the effect was not significant for the total neutron emission of 3.6 × 1018 on LHD.

Experimental tests of an infrared video bolometer on Alcator C-Mod.

A prototype of an infrared imaging bolometer (IRVB) was successfully tested on the Alcator C-Mod tokamak at the end of its 2016 campaign. The IRVB method interprets the power radiated from the plasma by measuring the temperature rise of a thin, ∼2 µm, Pt absorber that is placed in the torus vacuum and exposed, using a pinhole camera, to the full-spectrum of plasma's photon emission. The IRVB installed on C-Mod viewed the poloidal cross section of the core plasma and observed Ohmic and ion cyclotron range of frequency (ICRF)-heated plasmas. Analysis of total radiated power and on-axis emissivity from IRVB is summarized, and quantitative comparisons made to data from both resistive bolometers and AXUV diodes. IRVB results are clearly within a factor of two, but additional effort is needed for it to be used to fully support power exhaust research. The IRVB is shown to be immune to electromagnetic interference from ICRF which strongly impacts C-Mod's resistive bolometers. Results of the bench-top calibration are summarized, including a novel temperature calibration method useful for IRVBs.

A pilot investigation on impact of participation in a long-term follow-up clinic (LTFU) on breast cancer and cardiovascular screening among women who received chest radiation for Hodgkin lymphoma.

BACKGROUND: Women treated with chest radiation for Hodgkin lymphoma (HL) are at significantly increased risk of breast cancer and cardiovascular disease. HL survivors are recommended to have annual dual screening with mammogram (MMG) and breast magnetic resonance imaging (MRI). They are also recommended to undergo echocardiogram (echo) 5 years after completion of radiation. We performed a pilot study to characterize the women who are and are not receiving proper dual screening for breast cancer and baseline echo, and to examine the impact of a LTFU clinic consultation on screening. METHODS: A retrospective chart review of 114 women treated for HL at University of Minnesota (UMN) between 1993 and 2009 was performed. Demographics, disease and treatment history (age at diagnosis, stage, radiation dose and field, chemotherapy, recurrence) were assessed, as well as screening practices (MMG, MRI, both and echo), participation in LTFU clinic, and recommendations from providers. Data was summated in yes/no (y/n) format; statistical analysis was performed using chi-squared and Fisher's exact tests. Breast cancer and cardiovascular screening outcomes were compared by participation in the LTFU clinic (y/n) using Fisher's exact tests. P values < 0.05 were considered statistically significant. RESULTS: Forty-one of 114 women met inclusion criteria and had follow-up data for analysis. Median age at diagnosis was 29 years; 67.6% were diagnosed at stage IIa. Median dose of radiation was 3570 cGy. 56.1% participated in the LTFU clinic at the UMN. 36.6% had dual screening with both MMG and MRI, 41.5% had screening with only MMG, and 19.5% had no screening performed. Women were more likely to have dual screening if they were seen in LTFU clinic vs not seen in LTFU clinic (52.2 vs 16.7%, p = 0.02). 67.5% of women were screened with echo; women were also more likely to have screening with echo if seen in LTFU clinic vs not seen (86.4 vs 44.4%, p = 0.007). CONCLUSION: Many women are not getting the proper dual screening for breast cancer despite their increased risk, with only 36.6% of our study sample getting dual screening. Having a consultation in a LTFU clinic increases dual screening for breast cancer and echo screening for cardiovascular disease. Proper screening allows for detection of secondary breast cancer at earlier stages where treatment can be local therapy. Diagnosing CV disease early could allow for proper preventative treatment or intervention.

JNK1 controls adult hippocampal neurogenesis and imposes cell-autonomous control of anxiety behaviour from the neurogenic niche.

Promoting adult hippocampal neurogenesis is expected to induce neuroplastic changes that improve mood and alleviate anxiety. However, the underlying mechanisms remain largely unknown and the hypothesis itself is controversial. Here we show that mice lacking Jnk1, or c-Jun N-terminal kinase (JNK) inhibitor-treated mice, display increased neurogenesis in adult hippocampus characterized by enhanced cell proliferation and survival, and increased maturation in the ventral region. Correspondingly, anxiety behaviour is reduced in a battery of tests, except when neurogenesis is prevented by AraC treatment. Using engineered retroviruses, we show that exclusive inhibition of JNK in adult-born granule cells alleviates anxiety and reduces depressive-like behaviour. These data validate the neurogenesis hypothesis of anxiety. Moreover, they establish a causal role for JNK in the hippocampal neurogenic niche and anxiety behaviour, and advocate targeting of JNK as an avenue for novel therapies against affective disorders.

Evidence for neuroplastic compensation in the cerebral cortex of persons with depressive illness.

We yoked anatomical brain magnetic resonance imaging to a randomized, double-blind, placebo-controlled trial (RCT) of antidepressant medication for 10-week's duration in patients with dysthymia. The RCT study design mitigated ascertainment bias by randomizing patients to receive either duloxetine or placebo, and it supported true causal inferences about treatment effects on the brain by controlling treatment assignment experimentally. We acquired 121 anatomical scans: at baseline and end point in 41 patients and once in 39 healthy controls. At baseline, patients had diffusely thicker cortices than did healthy participants, and patients who had thicker cortices had proportionately less severe symptoms. During the trial, symptoms improved significantly more in medication-compared with placebo-treated patients; concurrently, thicknesses in medication-treated patients declined toward values in healthy controls, but they increased slightly, away from control values, in placebo-treated patients. Changes in symptom severity during the trial mediated the association of treatment assignment with the change in thickness, suggesting that the beneficial effects of medication on symptom severity were at least partially responsible for normalizing cortical thickness. Together our findings suggest that baseline cortical hypertrophy in medication-free patients likely represented a compensatory, neuroplastic response that attenuated symptom severity. Medication then reduced symptoms and lessened the need for compensation, thereby normalizing thickness. This is to the best of our knowledge the first study to report within an RCT a differential change in cortical morphology during medication treatment for depressive illness and the first to provide within an RCT in vivo evidence for the presence of neuroanatomical plasticity in humans.

JNK1 controls adult hippocampal neurogenesis and imposes cell-autonomous control of anxiety behaviour from the neurogenic niche.

This corrects the article DOI: 10.1038/mp.2016.203.

Early patient-reported outcomes versus objective function after total hip and knee arthroplasty: a prospective cohort study.

AIMS: The purpose of this study was to assess early physical function after total hip or knee arthroplasty (THA/TKA), and the correlation between patient-reported outcome measures, physical performance and actual physical activity (measured by actigraphy). PATIENTS AND METHODS: A total of 80 patients aged 55 to 80 years undergoing THA or TKA for osteoarthritis were included in this prospective cohort study. The main outcome measure was change in patient reported hip or knee injury and osteoarthritis outcome score (HOOS/KOOS) from pre-operatively until post-operative day 13 (THA) or 20 (TKA). Secondary measures were correlations to objectively assessed change in physical performance (paced-walk, chair-stand, stair-climb tests) at day 14 (THA) or 21 (TKA) and actual physical activity (actigraphy) measured at day 12 and 13 (THA) or 19 and 20 (TKA). RESULTS: Patients reported improved physical function (HOOS or KOOS) pre-operatively until day 13 (THA) or 20 (TKA) with a mean difference of 7 (95% confidence interval (CI) 1 to 13, p = 0.033) and 6 (95% CI 1 to 12, p = 0.033) percentage points, respectively. By contrast, objectively assessed physical function and activity declined, with no correlations between subjective and objective assessments for either THA or TKA patients (r2 ≤ 0.16, p ≥ 0.314). CONCLUSIONS: Early improvement in patient-reported physical function after THA/TKA does not correlate with objectively assessed function, and patient reported outcomes should not be used as the only measure of recovery. Cite this article: Bone Joint J 2017;99-B:1167-75.

An Overview of Mechanisms of Cry Toxin Resistance in Lepidopteran Insects.

Arthropods have the capacity to evolve resistance to insecticides and insecticidal traits in genetically modified crops. Resistance development among Lepidoptera is a common phenomenon, and a repertoire of resistance mechanisms to various Cry toxins have been identified from laboratory, greenhouse, and field studies in this insect order. Elucidation of such resistance mechanisms is crucial for developing IRM (insect resistance management) strategies to ensure sustainable use of genetically modified crops. This mini review provides a comprehensive overview of mechanisms of resistance that have been reported for lepidopteran pests. This study demonstrated that resistance mechanisms are highly complex, and the most common mechanism of resistance is altered binding sites. It is yet to be established whether all these altered binding sites are regulated by an MAPK signaling pathway, which might suggest a universal mechanism of resistance in lepidopterans.

In situ calibration of the foil detector for an infrared imaging video bolometer using a carbon evaporation technique.

The InfraRed imaging Video Bolometer (IRVB) is a useful diagnostic for the multi-dimensional measurement of plasma radiation profiles. For the application of IRVB measurement to the neutron environment in fusion plasma devices such as the Large Helical Device (LHD), in situ calibration of the thermal characteristics of the foil detector is required. Laser irradiation tests of sample foils show that the reproducibility and uniformity of the carbon coating for the foil were improved using a vacuum evaporation method. Also, the principle of the in situ calibration system was justified.

Design and characterization of a prototype divertor viewing infrared video bolometer for NSTX-U.

The InfraRed Video Bolometer (IRVB) is a powerful tool to measure radiated power in magnetically confined plasmas due to its ability to obtain 2D images of plasma emission using a technique that is compatible with the fusion nuclear environment. A prototype IRVB has been developed and installed on NSTX-U to view the lower divertor. The IRVB is a pinhole camera which images radiation from the plasma onto a 2.5 µm thick, 9 × 7 cm2 Pt foil and monitors the resulting spatio-temporal temperature evolution using an IR camera. The power flux incident on the foil is calculated by solving the 2D+time heat diffusion equation, using the foil's calibrated thermal properties. An optimized, high frame rate IRVB, is quantitatively compared to results from a resistive bolometer on the bench using a modulated 405 nm laser beam with variable power density and square wave modulation from 0.2 Hz to 250 Hz. The design of the NSTX-U system and benchtop characterization are presented where signal-to-noise ratios are assessed using three different IR cameras: FLIR A655sc, FLIR A6751sc, and SBF-161. The sensitivity of the IRVB equipped with the SBF-161 camera is found to be high enough to measure radiation features in the NSTX-U lower divertor as estimated using SOLPS modeling. The optimized IRVB has a frame rate up to 50 Hz, high enough to distinguish radiation during edge-localized-modes (ELMs) from that between ELMs.

Preliminary design of a tangentially viewing imaging bolometer for NSTX-U.

The infrared imaging video bolometer (IRVB) measures plasma radiated power images using a thin metal foil. Two different designs with a tangential view of NSTX-U are made assuming a 640 × 480 (1280 × 1024) pixel, 30 (105) fps, 50 (20) mK, IR camera imaging the 9 cm × 9 cm × 2 µm Pt foil. The foil is divided into 40 × 40 (64 × 64) IRVB channels. This gives a spatial resolution of 3.4 (2.2) cm on the machine mid-plane. The noise equivalent power density of the IRVB is given as 113 (46) µW/cm2 for a time resolution of 33 (20) ms. Synthetic images derived from Scrape Off Layer Plasma Simulation data using the IRVB geometry show peak signal levels ranging from ∼0.8 to ∼80 (∼0.36 to ∼26) mW/cm2.

Alterations in amygdala-prefrontal circuits in infants exposed to prenatal maternal depression.

Prenatal exposure to maternal depression is common and puts offspring at risk for developing a range of neuropsychiatric disorders. Despite its prevalence and adverse associations, neurobiological processes by which prenatal maternal depression (PMD) confers risk remain poorly understood. Maternal mood and fetal behavior were assessed between 34 and 37 gestational weeks. Using resting-state functional magnetic resonance imaging (fMRI) and diffusion MRI, we examined functional and structural connectivity within amygdala-prefrontal circuits in 64 infants (mean age=5.8±1.7 weeks) with (n=20) and without (n=44) in utero exposure to PMD. Resting fMRI and diffusion MRI both indicated atypical amygdala-prefrontal connectivity in PMD-exposed infants: Resting fMRI indicated increased inverse, or negative, functional connectivity between the amygdala and the dorsal prefrontal cortex (PFC), bilaterally, and diffusion MRI indicated decreased structural connectivity between the right amygdala and the right ventral PFC. Spectral dynamic causal modeling supported these findings suggesting altered amygdala-PFC effective (or directed) connectivity in PMD-exposed infants. Last, path analyses supported a mechanistic account relating PMD to a third-trimester fetal behavior: PMD alters amygdala-PFC connectivity, which in turn, is associated with an increase in fetal heart rate reactivity to in utero perturbation. These data suggest that the maturation and coordination of central and peripheral physiology are altered by prenatal exposure to maternal depression. To the best of our knowledge, this is the first study to directly associate infant MRI measures with a behavior-fetal heart rate response, and supports hypotheses that PMD-associated variations in the development of amygdala-PFC circuits are relevant for future neurobehavioral maturation.