177 research outputs found
Positivity of relative canonical bundles and applications
Given a family of canonically polarized manifolds, the
unique K\"ahler-Einstein metrics on the fibers induce a hermitian metric on the
relative canonical bundle . We use a global elliptic
equation to show that this metric is strictly positive on , unless
the family is infinitesimally trivial.
For degenerating families we show that the curvature form on the total space
can be extended as a (semi-)positive closed current. By fiber integration it
follows that the generalized Weil-Petersson form on the base possesses an
extension as a positive current. We prove an extension theorem for hermitian
line bundles, whose curvature forms have this property. This theorem can be
applied to a determinant line bundle associated to the relative canonical
bundle on the total space. As an application the quasi-projectivity of the
moduli space of canonically polarized varieties
follows.
The direct images , , carry natural hermitian metrics. We prove an
explicit formula for the curvature tensor of these direct images. We apply it
to the morphisms that are induced by the Kodaira-Spencer map and obtain a differential
geometric proof for hyperbolicity properties of .Comment: Supercedes arXiv:0808.3259v4 and arXiv:1002.4858v2. To appear in
Invent. mat
The perceived barriers to the inclusion of rainwater harvesting systems by UK house building companies
This work investigates the barriers that exist to deter the implementation of rainwater harvesting into new UK housing. A postal questionnaire was sent to a selection of large, medium and small house-builders distributed across the UK. Questions were asked concerning potential barriers to the inclusion of rainwater harvesting in homes separated into five sections; (1) institutional and regulatory gaps, (2) economic and financial constraints, (3) absence of incentives, (4) lack of information and technical knowledge, and (5) house-builder attitudes. The study concludes that although the knowledge of rainwater systems has increased these barriers are deterring house-builders from installing rainwater harvesting systems in new homes. It is further acknowledged that the implementation of rainwater harvesting will continue to be limited whilst these barriers remain and unless resolved, rainwater harvesting's potential to reduce the consumption of potable water in houses will continue to be limited
Szeg\"o kernel asymptotics and Morse inequalities on CR manifolds
We consider an abstract compact orientable Cauchy-Riemann manifold endowed
with a Cauchy-Riemann complex line bundle. We assume that the manifold
satisfies condition Y(q) everywhere. In this paper we obtain a scaling
upper-bound for the Szeg\"o kernel on (0, q)-forms with values in the high
tensor powers of the line bundle. This gives after integration weak Morse
inequalities, analogues of the holomorphic Morse inequalities of Demailly. By a
refined spectral analysis we obtain also strong Morse inequalities which we
apply to the embedding of some convex-concave manifolds.Comment: 40 pages, the constants in Theorems 1.1-1.8 have been modified by a
multiplicative constant 1/2 ; v.2 is a final updat
Drought impact in the Bolivian Altiplano agriculture associated with the El Niño–Southern Oscillation using satellite imagery data
Drought is a major natural hazard in the Bolivian Altiplano that causes large agricultural losses. However, the drought effect on agriculture varies largely on a local scale due to diverse factors such as climatological and hydrological conditions, sensitivity of crop yield to water stress, and crop phenological stage among others. To improve the knowledge of drought impact on agriculture, this study aims to classify drought severity using vegetation and land surface temperature data, analyse the relationship between drought and climate anomalies, and examine the spatio-temporal variability of drought using vegetation and climate data. Empirical data for drought assessment purposes in this area are scarce and spatially unevenly distributed. Due to these limitations we used vegetation, land surface temperature (LST), precipitation derived from satellite imagery, and gridded air temperature data products. Initially, we tested the performance of satellite precipitation and gridded air temperature data on a local level. Then, the normalized difference vegetation index (NDVI) and LST were used to classify drought events associated with past El Niño–Southern Oscillation (ENSO) phases. It was found that the most severe drought events generally occur during a positive ENSO phase (El Niño years). In addition, we found that a decrease in vegetation is mainly driven by low precipitation and high temperature, and we identified areas where agricultural losses will be most pronounced under such conditions. The results show that droughts can be monitored using satellite imagery data when ground data are scarce or of poor data quality. The results can be especially beneficial for emergency response operations and for enabling a proactive approach to disaster risk management against droughts
Cisplatin and Oxaliplatin Toxicity: Importance of Cochlear Kinetics as a Determinant for Ototoxicity
Background
Cisplatin is a commonly used platinum anti-cancer drug. Regrettably cisplatin
has dose-limiting ototoxic side effects, e.g. the drug can induce an irreversible
hearing loss. The ototoxic mechanisms of cisplatin have not been
elucidated in the human ear and no clinically useful oto-protectors are yet
available. Cisplatin is a necessary part of many treatment regimes. Its beneficial
therapeutic effects might be reduced if cisplatin was excluded from the
treatment in order to protect the hearing function. In this work the ototoxic
effects of cisplatin are studied with the aim to better understand the mechanisms
behind the irreversible hearing loss induced by this drug. Oxaliplatin is
a second generation platinum-derivative anti-cancer drug, free from ototoxic
side effects in clinical practice. The effects of oxaliplatin on the inner ear have
been studied in this work and the results are compared with cisplatin treatment.
The two drugs differ regarding both anti-cancer effects and side effects,
which could be attributed to differences in pharmacokinetic factors, cellular
uptake and apoptotic mechanisms. The thioredoxin redox system with the
enzyme thioredoxin reductase (TrxR) was studied in cochleae due to a suggested
DNA-independent apoptotic mechanism of the hair cells. The cochlear
pharmacokinetics of cisplatin was assessed and the transport protein organic
cation transporter 2 (OCT2) was studied in relation to the ototoxic effect of
cisplatin.
Material and methods
Cultured human colon carcinoma cells and cell cultures of rat organ of Corti
were used for apoptosis studies in vitro following exposure to cisplatin and
oxaliplatin. Cisplatin and oxaliplatin were administered i.v. to guinea pigs,
followed by in vivo sampling of blood, cerebrospinal fluid (CSF) and scala
tympani (ST) perilymph. Liquid chromatography with post-column derivatization
was used to determine the concentration of parent drug in the samples.
Electrophysiological hearing thresholds and the loss of hair cells were assessed
to evaluate their ototoxic effects. Phenformin, a potential blocker of
OCT2 was administered and the ototoxic side effect of cisplatin was evaluated.
For immunohistochemical studies, cochlea from rat, guinea pig and pig
were used, where TrxR and OCT2 were evaluated in the cochlea. TrxR-assays
were used to measure the TrxR activity in cochlear tissue, both in vivo and in
vitro.
Results
The results from the in vitro studies showed that addition of either cisplatin
or oxaliplatin to the culture medium in organ of Corti cell cultures caused a
similar amount of outer hair cell loss and inhibition of TrxR activity. Cisplatin
exposure to cultured human colon carcinoma cells also reduced the activity
of TrxR. The results from the in vivo studies showed that a considerable concentration
of cisplatin was present in ST perilymph as compared with weak
concentrations of oxaliplatin after high dose oxaliplatin i.v. Ten minutes after
cisplatin administration, its concentration in ST perilymph was 4-fold higher
in the basal turn of the cochlea as compared to the apex. Cisplatin could be
analysed in ST perilymph for up to 120 min. Phenformin i.v. did not reduce
the ototoxic side-effect of cisplatin. Positive immunoreactivity to TrxR was
evident in both hair cells and spiral ganglion cells. Futhermore, OCT2 was
expressed in the supporting cells of organ of Corti and in the spiral ganglion
cells.
Conclusion
The transport of cisplatin to the vulnerable cells of hearing seems to be of major
importance for the ototoxic effects. An early high concentration of cisplatin
in the base of the cochlea and delayed elimination of cisplatin from ST perilymph
may be related to the cisplatin-induced loss of outer hair cells in the
basal turn of the cochlea. Cisplatin and oxaliplatin both cause similar ototoxic
effects when the organ of Corti is directly exposed in vitro. The thioredoxin
redox system with the TrxR enzyme may well play a critical role in cisplatininduced
ototoxicity. The presence of OCT2 in the supporting cells indicates
that this transport protein is primarily not involved in the uptake of cisplatin
from the systemic circulation but rather from the deeper compartments of
the cochlea. The knowledge elicited in this work will hopefully suggest objectives
for further studies in order to develop oto-protective treatments to
preserve the hearing of cisplatin treated patients
The impact of inflammatory bowel disease on sexual health in men: A scoping review.
AIMS AND OBJECTIVES: To review the literature on the impact of inflammatory bowel disease on the sexual health of men, and make recommendations for nursing practice and research. BACKGROUND: Inflammatory bowel disease is a chronic condition of the gastrointestinal tract, causing symptoms that may impact upon sexual health. Specialist nurses are well positioned to assess and manage sexual health, but there is a lack of clinical guidance, especially in relation to men. DESIGN: A systematic scoping review following the Arksey and O'Malley (2005) framework reported in line with the PRISMA-ScR checklist (Tricco et al. 2018). METHODS: OVID MEDLINE ALL [R], OVID EMBASE [R], OVID PsychINFO, EBSCO CINAHL Complete, The Cochrane Library and ProQuest were searched. Inclusion and exclusion criteria were applied independently by two reviewers. Data was extracted, charted and summarised from eligible studies. RESULTS: Thirty-one studies met the inclusion criteria. These were synthesised under three categories: mediators, moderators, and descriptors of sexual health. Depression, disease activity and surgery were the most commonly cited disease-related factors to affect sexual health in men. The most commonly used assessment tool was The International Index of Erectile Function. Descriptors of function included; frequency of intercourse, libido and the ability to maintain a desired sexual role. CONCLUSIONS: The effect of inflammatory bowel disease on sexual health in men involves a complex interaction of physical and psychosocial factors. Researchers must explore areas outside of erectile function to understand how the disease impacts sexuality, sexual well-being and masculinity. This can be achieved through qualitative exploration of patient, partner and health professional experiences. Relevance to clinical practice A holistic nursing assessment of men with inflammatory bowel disease should include sexual health. Developing understanding of how the disease influences sexual interaction and expression will facilitate support that is relevant, accessible and of value to men living with the disease
Cathepsin B-like and cell death in the unicellular human pathogen Leishmania
In several studies reporting cell death (CD) in lower eukaryotes and in the human protozoan parasite Leishmania, proteolytic activity was revealed using pan-caspase substrates or inhibitors such as carbobenzoxy-valyl-alanyl-aspartyl-[O-methyl]-fluoromethylketone (Z-VAD-FMK). However, most of the lower eukaryotes do not encode caspase(s) but MCA, which differs from caspase(s) in its substrate specificity and cannot be accountable for the recognition of Z-VAD-FMK. In the present study, we were interested in identifying which enzyme was capturing the Z-VAD substrate. We show that heat shock (HS) induces Leishmania CD and leads to the intracellular binding of Z-VAD-FMK. We excluded binding and inhibition of Z-VAD-FMK to Leishmania major metacaspase (LmjMCA), and identified cysteine proteinase C (LmjCPC), a cathepsin B-like (CPC) enzyme, as the Z-VAD-FMK binding enzyme. We confirmed the specific interaction of Z-VAD-FMK with CPC by showing that Z-VAD binding is absent in a Leishmania mexicana strain in which the cpc gene was deleted. We also show that parasites exposed to various stress conditions release CPC into a soluble fraction. Finally, we confirmed the role of CPC in Leishmania CD by showing that, when exposed to the oxidizing agent hydrogen peroxide (H2O2), cpc knockout parasites survived better than wild-type parasites (WT). In conclusion, this study identified CPC as the substrate of Z-VAD-FMK in Leishmania and as a potential additional executioner protease in the CD cascade of Leishmania and possibly in other lower eukaryotes
Determinants of female sexual function in inflammatory bowel disease: a survey based cross-sectional analysis
<p>Abstract</p> <p>Background</p> <p>Sexual function is impaired in women with inflammatory bowel disease (IBD) as compared to normal controls. We examined disease specific determinants of different aspects of low sexual function.</p> <p>Methods</p> <p>Women with IBD aged 18 to 65 presenting to the university departments of internal medicine and surgery were included. In addition, a random sample from the national patients organization was used (separate analyses). Sexual function was assessed by the Brief Index of Sexual Function in Women, comprising seven different domains of sexuality. Function was considered impaired if subscores were < -1 on a z-normalized scale. Results are presented as age adjusted odds ratios with 95% CI based on multiple logistic regression.</p> <p>Results</p> <p>336 questionnaires were included (219 Crohn's disease, 117 ulcerative colitis). Most women reported low sexual activity (63%; 17% none at all, 20% moderate or high activity). Partnership satisfaction was high in spite of low sexual interest in this group. Depressed mood was the strongest predictor of low sexual function scores in all domains. Urban residency and higher socioecomic status had a protective effect. Disease activity was moderately associated with low desire (OR 1.8, 95% CI 1.0 to 3.2). Severity of the disease course impacted most on intercourse frequency (OR 2.3, 95% CI 1.4 to 4.7). Lubrication problems were more common in smokers (OR 2.5, 95% CI 1.3 to 5.1).</p> <p>Conclusion</p> <p>Mood disturbances and social environment impacted more on sexual function in women with IBD than disease specific factors. Smoking is associated with lubrication problems.</p
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