Star formation inside a galactic outflow.

Recent observations have revealed massive galactic molecular outflows that may have the physical conditions (high gas densities) required to form stars. Indeed, several recent models predict that such massive outflows may ignite star formation within the outflow itself. This star-formation mode, in which stars form with high radial velocities, could contribute to the morphological evolution of galaxies, to the evolution in size and velocity dispersion of the spheroidal component of galaxies, and would contribute to the population of high-velocity stars, which could even escape the galaxy. Such star formation could provide in situ chemical enrichment of the circumgalactic and intergalactic medium (through supernova explosions of young stars on large orbits), and some models also predict it to contribute substantially to the star-formation rate observed in distant galaxies. Although there exists observational evidence for star formation triggered by outflows or jets into their host galaxy, as a consequence of gas compression, evidence for star formation occurring within galactic outflows is still missing. Here we report spectroscopic observations that unambiguously reveal star formation occurring in a galactic outflow at a redshift of 0.0448. The inferred star-formation rate in the outflow is larger than 15 solar masses per year. Star formation may also be occurring in other galactic outflows, but may have been missed by previous observations owing to the lack of adequate diagnostics.

The complex and often confusing history, histology and histogenesis of mesonephric, STK11 adnexal tumour and mesonephric-like neoplasms of the upper female genital tract (including broad ligament).

Mesonephric lesions in the female genital tract are uncommon, with those arising from the upper tract being much less frequent than those developing in the lower tract (mesonephric hyperplasia and carcinoma). The most common upper tract lesions include rete cyst/cystadenoma and female adnexal tumour of Wolffian origin (FATWO). The integration of morphological, immunohistochemical and molecular studies on FATWOs has enabled recognition of a novel entity, the STK11 adnexal tumour, which is often associated with Peutz-Jeghers syndrome (~50%) and frequently has a salivary gland morphology but an unknown origin. Similarly, 'mesonephric-like' adenocarcinoma, an entity with striking similarities to mesonephric carcinoma but currently favoured to be of Müllerian derivation based on its association with other Müllerian tumours and molecular findings, has also been recently described, and may histologically mimic both FATWOs and STK11 adnexal tumours. In this review, we provide a historical overview of upper female genital tract mesonephric proliferations and discuss mesonephric lesions, STK11 adnexal tumour, mesonephric-like adenocarcinoma, and mimickers, the most common being endometrioid carcinoma.

Effect of olive leaves feeding on phenolic composition and lipolytic volatile profile in goat milk.

The aim of this study was to evaluate phenolic composition, antioxidant potential, and lipolytic events in raw milk obtained from goat fed a dietary supplementation with olive leaves (OL), a by-product of the olive oil production chain. For this purpose, 30 Saanen goats were randomly allocated into 2 groups of 15 goats each: the control group received a standard diet that was prepared by taking into account the nutritional needs of lactating goats, whereas the experimental group (EG) was fed with an OL-supplemented diet (10% on a dry matter basis). At the end of the 30 d of the trial, the individual milk samples were collected and immediately analyzed for total phenolic content and antioxidant activity (AOA). Subsequently, the individual phenolic compounds have been identified and quantified through an ultra-high-performance liquid chromatography system and a characterization of free fatty acids released in milk has been performed. The results showed a positive effect of dietary OL supplementation in improving total phenolic content and AOA; furthermore, 19 phenolic compounds, including phenolic acids, flavonoids, simple phenols, and secoiridoids, have been identified in EG milk. In addition to this, a reduced accumulation of free fatty acids has been found in EG milk, and this finding leads us to hypothesize an inhibitory action of the identified phenolic compounds toward the enzymes responsible for lipolytic events. The use of the molecular docking approach verified the interactions, defining a fairly interesting framework for cinnamic acid, which should be able to noncovalently bind these enzymes, interfering with the recruitment of the substrate and therefore, slowing down their hydrolytic activity. In any case, this information will be subjected to in vitro evaluations for an accurate characterization of the biochemical mechanisms that can be established in milk naturally enriched with bioactive compounds.

Appraisal of patient-reported outcome measures in analogous diseases and recommendations for use in phase II and III clinical trials of pyruvate kinase deficiency.

PURPOSE: Pyruvate kinase deficiency (PKD) is a rare disease and understanding of its epidemiology and associated burden remains limited. With no current curative therapy, clinical manifestations can be life threatening, clinically managed by maintaining adequate hemoglobin levels through transfusion and subsequent support, but with frequent complications. Treatment goals are to maintain/improve the patient's quality of life. With new therapies, reliable, valid, and relevant patient-reported outcome (PRO) tools are required for use in clinical trials. METHODS: Systematic literature search identified no current PRO tools for capturing/measuring the impact of PKD and treatments in clinical trials. Therefore, the search strategy was revised to consider conditions analogous to PKD in terms of symptoms and impacts that might serve as parallels to the experience in PKD; this included sickle cell anemia, thalassemia, and hemolytic anemia. Psychometric properties, strengths, and weakness of selected appropriate PRO instruments were compared, and recommendations made for choice of PRO tools. RESULTS: In adult populations, EORTC QLQ C30 and SF-36v2 are recommended, the former being a basic minimum, covering generic HRQoL, and core symptoms such as fatigue. In pediatric populations, PedsQL Generic Core Scale to measure HRQoL and PedsQL MFS scale to measure fatigue are recommended. CONCLUSIONS: Some symptoms/life impacts may be unique to PKD and not observable in analogous conditions. A 'Physico-Psychosocial Model' derived from the 'Medical Model' is proposed to form the basis for a hypothesized conceptual framework to address the development of PKD-specific PRO instruments.

Gynecological neoplasms associated with paraneoplastic hypercalcemia.

Approximately 5% of gynecological malignancies are associated with paraneoplastic hypercalcemia. Awareness of its association with certain tumor types allows for earlier disease detection and facilitates monitoring of treatment response and disease recurrence. We review the salient clinicopathological features, differential diagnosis and management issues in some of these gynecological tumors, namely: small cell carcinoma, hypercalcemic type; ovarian clear cell carcinoma, dysgerminoma and juvenile granulosa cell tumors.

Stromal invasion pattern identifies patients at lowest risk of lymph node metastasis in HPV-associated endocervical adenocarcinomas, but is irrelevant in adenocarcinomas unassociated with HPV.

OBJECTIVE: The Silva invasion pattern-based classification system stratifies endocervical adenocarcinomas (ECAs) into 3 categories corresponding to risk of metastasis and recurrence, but has only been evaluated for HPV-associated ECAs of usual type. We examined whether the Silva system is applicable to all endocervical adenocarcinomas, especially those not associated with HPV. METHODS: Complete slide sets from 341 surgical specimens of ECA were collected from 7 institutions worldwide. All specimens were associated with clinical records covering at least 5 years of follow-up. Tumors were classified as HPV-associated (HPVA) or not (NHPVA) by both morphology and detection of HPV using in situ hybridization. Recurrence and survival were analyzed by multivariate Mantel-Haenszel methods. RESULTS: Most specimens (292; 85.6%) were HPVA, while 49 (14.3%) were NHPVA. All NHPVAs were Silva pattern C, while 76.0% of HPVAs were pattern C, 14.7% pattern A, and 9.3% pattern B. Including both HPVAs and NHPVAs, lymphovascular invasion (LVI) was detected in 0% of pattern A, 18.5% of pattern B and 62.6% of pattern C cases (p < 0.001). None of the pattern A or B cases were associated with lymph node metastases (LNM), in contrast to pattern C cases (21.8%). Among patients with Silva pattern C ECA, those with HPVA tumors had a lower recurrence rate and better survival than those with NHPVA; however, when adjusted for stage at diagnosis, the difference in recurrence and mortality was small and not statistically significant. CONCLUSIONS: Application of the Silva system is only relevant in HPVA cervical adenocarcinoma.

Fourier transform holography with high harmonic spectra for attosecond imaging applications.

We demonstrate a method of using a Fourier holographic technique to utilize attosecond soft x-ray pulses to image nanometer-scale objects. A discrete frequency comb of laser-generated high-order harmonics, yielding a train of attosecond pulses, has been used to record spatially and spectrally resolved images. The individual wavelengths were also combined to form a single image, albeit with lower spatial resolution, demonstrating the applicability of the method to using isolated attosecond pulses with continuous bandwidths.

Demonstration of a Circularly Polarized Plasma-Based Soft-X-Ray Laser.

We report the first experimental demonstration of a laser-driven circularly polarized soft-x-ray laser chain. It has been achieved by seeding a 32.8 nm Kr ix plasma amplifier with a high-order harmonic beam, which has been circularly polarized using a four-reflector polarizer. Our measurements testify that the amplified radiation maintains the initial polarization of the seed pulse in good agreement with our Maxwell-Bloch modeling. The resulting fully circular soft-x-ray laser beam exhibits a Gaussian profile and yields about 10^{10} photons per shot, fulfilling the requirements for laboratory-scale photon-demanding application experiments.

Old versus new FIGO staging systems in predicting overall survival in patients with uterine leiomyosarcoma: a study of 86 cases.

OBJECTIVES: Uterine leiomyosarcoma (uLMS) was staged using the FIGO system for endometrial cancers. The new FIGO system takes into consideration tumor size disregarding myometrial and cervical involvement. We aimed to compare the two systems and see which more accurately predicts overall survival (OS). METHODS: 86 patients with uLMS (1984-2010) were retrospectively staged using both FIGO systems. Mean OS rates were estimated using the Kaplan-Meier method. RESULTS: More patients had stage-I disease by the new FIGO system (42 versus 33). Five versus 18 and 27 versus 5 had old and new stage-II and III diseases respectively. Five and 4 patients with old stage II and III uLMS respectively were downstaged to stage I while 18 with old stage III were downstaged to stage II. Median follow-up was 23.5 months with a median OS of 114 (95% CI, 61-166) months. Although patients with stage I tumors had a higher mean OS rate compared to those with higher stage disease by either system, patients with old stage II-IV disease showed similar mean OS rates, with stage III-IV patients having a slightly better mean OS and a similar trend was observed with the new system. Patients with new FIGO stage III had a higher mean OS rate than those with stage II or IV disease (37.6 versus 28.1 and 34.3 months). Nonetheless, no statistical significant differences were seen in OS according to stage using either system (p=0.786 and p=0.400 respectively). CONCLUSION: Neither FIGO staging system is ideal in classifying patients into four clinically significant stages.

Correlation of tumor size with other prognostic factors in uterine serous carcinoma: a large multi-institutional study.

OBJECTIVE: Uterine serous carcinoma (USC) constitutes 10% of uterine cancers but ~40% of deaths. Tumor size is a known prognostic factor in other solid tumors. In endometriod cancers it is one element used to identify the need for complete staging, while its significance in USC is debated. Therefore tumor size was examined as an independent prognostic factor. METHODS: Clinical and pathologic variables were recorded for 236 institutional patients, and those patients in the SEER database with USC. Chi-square and Fisher exact t-tests were utilized and survival data generated via Kaplan-Meier method; multivariate analysis was performed via cox-regression. RESULTS: The patients' mean age was 67.2 years (range 40-91). Survival ranged from 0 to 184 months (mean 42.8). We used a tumor size cut-off of 1cm and noted significant associations with myometrial invasion (p<0.0001), angiolymphatic invasion (p<0.0001), peritoneal washings (p=0.03), stage (p=0.015) and positive lymph nodes (p=0.05). Furthermore, recurrence was associated with larger tumors (p=0.03). In multivariate analysis, extra-uterine disease was the only factor associated with both recurrence and survival. Review of the SEER database noted association of larger tumors with lymph node involvement and a significant survival advantage with tumors <1cm in both univariate and multivariate analysis. CONCLUSIONS: Treatment options for USC are often predicated on the surgical stage and therefore components of the staging are vitally important. The 1cm tumor-size cut-off should be studied prospectively as a prognostic indicator of survival and recurrence in USC and considered for inclusion in USC staging.

Two predicted α-helices within the prion-like domain of TIAR-1 play a crucial role in its association with stress granules in Caenorhabditis elegans.

Stress granules (SGs) are sites for mRNA storage, protection, and translation repression. TIA1 and TIAR1 are two RNA-binding proteins that are key players in SGs formation in mammals. TIA1/TIAR have a prion-like domain (PrD) in their C-terminal that promotes liquid-phase separation. Lack of any TIA1/TIAR has severe consequences in mice. However, it is not clear whether the failure to form proper SGs is the cause of any of these problems. We disrupted two predicted α-helices within the prion-like domain of the Caenohabditis elegans TIA1/TIAR homolog, TIAR-1, to test whether its association with SGs is important for the nematode. We found that tiar-1 PrD mutant animals continued to form TIAR-1 condensates under stress in the C. elegans gonad. Nonetheless, TIAR-1 condensates appeared fragile and disassembled quickly after stress. Apparently, the SGs continued to associate regularly as observed with CGH-1, an SG marker. Like tiar-1-knockout nematodes, tiar-1 PrD mutant animals exhibited fertility problems and a shorter lifespan. Notwithstanding this, tiar-1 PrD mutant nematodes were no sensitive to stress. Our data demonstrate that the predicted prion-like domain of TIAR-1 is important for its association with stress granules. Moreover, this domain may also play a significant role in various TIAR-1 functions unrelated to stress, such as fertility, embryogenesis and lifespan.

Cancer-associated mesothelial cells are regulated by the anti-Müllerian hormone axis.

Cancer-associated mesothelial cells (CAMCs) in the tumor microenvironment are thought to promote growth and immune evasion. We find that, in mouse and human ovarian tumors, cancer cells express anti-Müllerian hormone (AMH) while CAMCs express its receptor AMHR2, suggesting a paracrine axis. Factors secreted by cancer cells induce AMHR2 expression during their reprogramming into CAMCs in mouse and human in vitro models. Overexpression of AMHR2 in the Met5a mesothelial cell line is sufficient to induce expression of immunosuppressive cytokines and growth factors that stimulate ovarian cancer cell growth in an AMH-dependent way. Finally, syngeneic cancer cells implanted in transgenic mice with Amhr2-/- CAMCs grow significantly slower than in wild-type hosts. The cytokine profile of Amhr2-/- tumor-bearing mice is altered and their tumors express less immune checkpoint markers programmed-cell-death 1 (PD1) and cytotoxic T lymphocyte-associated protein 4 (CTLA4). Taken together, these data suggest that the AMH/AMHR2 axis plays a critical role in regulating the pro-tumoral function of CAMCs in ovarian cancer.

Gain lifetime measurement of a Ni-like Ag soft X-ray laser.

Experimental results of a two-stage Ni-like Ag soft X-ray laser operated in a seed-amplifier configuration are presented. Both targets were pumped applying the double-pulse grazing incidence technique with intrinsic travelling wave excitation. The injection of the seed X-ray laser into the amplifier target was realized by a spherical mirror. The results show amplification of the seed X-ray laser and allow for a direct measurement of the gain lifetime. The experimental configuration is suitable for providing valuable input for computational simulations.

A supernova origin for dust in a high-redshift quasar.

Interstellar dust plays a crucial role in the evolution of the Universe by assisting the formation of molecules, by triggering the formation of the first low-mass stars, and by absorbing stellar ultraviolet-optical light and subsequently re-emitting it at infrared/millimetre wavelengths. Dust is thought to be produced predominantly in the envelopes of evolved (age >1 Gyr), low-mass stars. This picture has, however, recently been brought into question by the discovery of large masses of dust in the host galaxies of quasars at redshift z > 6, when the age of the Universe was less than 1 Gyr. Theoretical studies, corroborated by observations of nearby supernova remnants, have suggested that supernovae provide a fast and efficient dust formation environment in the early Universe. Here we report infrared observations of a quasar at redshift 6.2, which are used to obtain directly its dust extinction curve. We then show that such a curve is in excellent agreement with supernova dust models. This result demonstrates a supernova origin for dust in this high-redshift quasar, from which we infer that most of the dust at high redshifts probably has the same origin.

Quantitative analysis of oxysterols in zebrafish embryos by HPLC-MS/MS.

Zebrafish is an in vivo model used in toxicology to estimate the effects of xenobiotics and their teratogenic consequences. The knowledge of the oxysterols profile in zebrafish, during early embryonic stages, provides important information on the role and biological function of these molecules. This work reports the development and validation of a LC-MS/MS method for the determination of 7 different oxysterols in zebrafish embryos. Sample was treated with a combination of liquid/liquid extraction (LLE) followed by micro solid phase extraction (µSPE) clean-up in order to remove matrix interference and obtain a suitable enrichment factor of the analytes. The method was validated on 2 different embryos growing stages, 3-4 and 24 h post fertilization (hpf), as slight differences in terms of recovery and matrix effect were shown. The validation results provided good accuracy (bias ≤17%; 20% at LOQ) and repeatability (≤15%; ≤19% at LOQ), with low LOQs in the range 22 and 65 pg on 100 embryos sample, without any analyte derivatization, demonstrating the suitability of this analytical method as a useful tool to understand the correlation between oxysterols profile and developmental abnormalities induced by xenobiotic exposure.

Nonlinear ionization dynamics of hot dense plasma observed in a laser-plasma amplifier.

Understanding the behaviour of matter under conditions of extreme temperature, pressure, density and electromagnetic fields has profound effects on our understanding of cosmologic objects and the formation of the universe. Lacking direct access to such objects, our interpretation of observed data mainly relies on theoretical models. However, such models, which need to encompass nuclear physics, atomic physics and plasma physics over a huge dynamic range in the dimensions of energy and time, can only provide reliable information if we can benchmark them to experiments under well-defined laboratory conditions. Due to the plethora of effects occurring in this kind of highly excited matter, characterizing isolated dynamics or obtaining direct insight remains challenging. High-density plasmas are turbulent and opaque for radiation below the plasma frequency and allow only near-surface insight into ionization processes with visible wavelengths. Here, the output of a high-harmonic seeded laser-plasma amplifier using eight-fold ionized krypton as the gain medium operating at a 32.8 nm wavelength is ptychographically imaged. A complex-valued wavefront is observed in the extreme ultraviolet (XUV) beam with high resolution. Ab initio spatio-temporal Maxwell-Bloch simulations show excellent agreement with the experimental observations, revealing overionization of krypton in the plasma channel due to nonlinear laser-plasma interactions, successfully validating this four-dimensional multiscale model. This constitutes the first experimental observation of the laser ion abundance reshaping a laser-plasma amplifier. The presented approach shows the possibility of directly modelling light-plasma interactions in extreme conditions, such as those present during the early times of the universe, with direct experimental verification.

Optimization of soft x-ray amplifier by tailoring plasma hydrodynamics.

Plasma-based seeded soft x-ray lasers have the potential to generate a high-energy, highly coherent, short pulse beam. Owing to their high density, plasmas created by interaction of an intense laser with a solid target should store the highest amount of energy among all plasma amplifiers. However, to date output energy from seeded solid amplifiers remains as low as 60 nJ. We demonstrated that careful tailoring of the plasma shape is crucial for extracting energy stored in the plasma. With 1-mm-wide plasma, energy as high as 20 microJ in sub-ps pulses is achievable. With such tailored plasma, gain and pumping efficiency have been increased by nearly a factor of 10 as compared to the narrower plasma amplifiers studied here.

Present and future schistosomiasis control activities with support from the Schistosomiasis Control Initiative in West Africa.

Since 2004 the West African countries of Burkina Faso, Mali and Niger have implemented national schistosomiasis and soil-transmitted helminthiasis control programmes with financial and technical support from the Schistosomiasis Control Initiative (SCI). In the first three years of the control programmes, nearly 13.5 million doses of praziquantel and albendazole have been administered against schistosomiasis and soil-transmitted helminthiasis with coverage rates varying between 67.0% and 93.9%. These treatments have resulted in a reduction of the prevalence and intensity of Schistosoma infection in the sentinel cohorts that were set up to monitor and evaluate the national control programmes. The challenges currently faced by these national control programmes are the ability to maintain the reduction in morbidity achieved thus far due to the mass treatment campaigns and ensuring sustainability. For reinforcement of surveillance, the establishment of a geographical information system is suggested in order to contribute towards enhanced sustainability of these programmes. Our new working hypothesis is that targeted control accompanied by periodic mass treatment campaigns (every two to three years) can contribute to maintaining the low levels of morbidity achieved thus far. The implementation of integrated neglected tropical disease control programmes in these countries will provide means to ensure the financial sustainability of control activities for the years to come.

The Schistosomiasis Control Initiative (SCI): rationale, development and implementation from 2002-2008.

Schistosomiasis remains one of the most prevalent parasitic diseases in developing countries. After malaria, schistosomiasis is the most important tropical disease in terms of human morbidity with significant economic and public health consequences. Although schistosomiasis has recently attracted increased focus and funding for control, it has been estimated that less than 20% of the funding needed to control the disease in Africa is currently available. In this article the following issues are discussed: the rationale, development and objectives of the Schistosomiasis Control Initiative (SCI)-supported programmes; the management approaches followed to achieve implementation by each country; mapping, monitoring and evaluation activities with quantifiable impact of control programmes; monitoring for any potential drug resistance; and finally exit strategies within each country. The results have demonstrated that morbidity due to schistosomiasis has been reduced by the control programmes. While challenges remain, the case for the control of schistosomiasis has been strengthened by research by SCI teams and the principle that a national programme using 'preventive chemotherapy' can be successfully implemented in sub-Saharan Africa, whenever the resources are available. SCI and partners are now actively striving to raise further funds to expand the coverage of integrated control of neglected tropical diseases (NTDs) in sub-Saharan Africa.