Measurement of the 2νßß Decay Rate and Spectral Shape of

Neutrinoless double beta decay (0νßß) is a yet unobserved nuclear process that would demonstrate Lepton number violation, a clear evidence of beyond standard model physics. The process two neutrino double beta decay (2νßß) is allowed by the standard model and has been measured in numerous experiments. In this Letter, we report a measurement of 2νßß decay half-life of ^{100}Mo to the ground state of ^{100}Ru of [7.07±0.02(stat)±0.11(syst)]×10^{18} yr by the CUPID-Mo experiment. With a relative precision of ±1.6% this is the most precise measurement to date of a 2νßß decay rate in ^{100}Mo. In addition, we constrain higher-order corrections to the spectral shape, which provides complementary nuclear structure information. We report a novel measurement of the shape factor ξ_{3,1}=0.45±0.03(stat)±0.05(syst) based on a constraint on the ratio of higher-order terms from theory, which can be reliably calculated. This is compared to theoretical predictions for different nuclear models. We also extract the first value for the effective axial vector coupling constant obtained from a spectral shape study of 2νßß decay.

New Limit for Neutrinoless Double-Beta Decay of

The CUPID-Mo experiment at the Laboratoire Souterrain de Modane (France) is a demonstrator for CUPID, the next-generation ton-scale bolometric 0νßß experiment. It consists of a 4.2 kg array of 20 enriched Li_{2}^{100}MoO_{4} scintillating bolometers to search for the lepton-number-violating process of 0νßß decay in ^{100}Mo. With more than one year of operation (^{100}Mo exposure of 1.17 kg×yr for physics data), no event in the region of interest and, hence, no evidence for 0νßß is observed. We report a new limit on the half-life of 0νßß decay in ^{100}Mo of T_{1/2}>1.5×10^{24} yr at 90% C.I. The limit corresponds to an effective Majorana neutrino mass ⟨m_{ßß}⟩<(0.31-0.54) eV, dependent on the nuclear matrix element in the light Majorana neutrino exchange interpretation.

First Germanium-Based Constraints on Sub-MeV Dark Matter with the EDELWEISS Experiment.

We present the first Ge-based constraints on sub-MeV/c^{2} dark matter (DM) particles interacting with electrons using a 33.4 g Ge cryogenic detector with a 0.53 electron-hole pair (rms) resolution, operated underground at the Laboratoire Souterrain de Modane. Competitive constraints are set on the DM-electron scattering cross section, as well as on the kinetic mixing parameter of dark photons down to 1 eV/c^{2}. In particular, the most stringent limits are set for dark photon DM in the 6 to 9 eV/c^{2} range. These results demonstrate the high relevance of Ge cryogenic detectors for the search of DM-induced eV-scale electron signals.

Deep phenotyping of facioscapulohumeral muscular dystrophy type 2 by magnetic resonance imaging.

BACKGROUND AND PURPOSE: The aim was to define the radiological picture of facioscapulohumeral muscular dystrophy 2 (FSHD2) in comparison with FSHD1 and to explore correlations between imaging and clinical/molecular data. METHODS: Upper girdle and/or lower limb muscle magnetic resonance imaging scans of 34 molecularly confirmed FSHD2 patients from nine European neuromuscular centres were analysed. T1-weighted and short-tau inversion recovery (STIR) sequences were used to evaluate the global pattern and to assess the extent of fatty replacement and muscle oedema. RESULTS: The most frequently affected muscles were obliquus and transversus abdominis, semimembranosus, soleus and gluteus minimus in the lower limbs; trapezius, serratus anterior, latissimus dorsi and pectoralis major in the upper girdle. Iliopsoas, popliteus, obturator internus and tibialis posterior in the lower limbs and subscapularis, spinati, sternocleidomastoid and levator scapulae in the upper girdle were the most spared. Asymmetry and STIR hyperintensities were consistent features. The pattern of muscle involvement was similar to that of FSHD1, and the combined involvement of trapezius, abdominal and hamstring muscles, together with complete sparing of iliopsoas and subscapularis, was detected in 91% of patients. Peculiar differences were identified in a rostro-caudal gradient, a predominant involvement of lower limb muscles compared to the upper girdle, and in the higher percentage of STIR hyperintensities in FSHD2. CONCLUSION: This multicentre study defines the pattern of muscle involvement in FSHD2, providing useful information for diagnostics and clinical trial design. Both similarities and differences between FSHD1 and FSHD2 were detected, which is also relevant to better understand the pathogenic mechanisms underlying the FSHD-related disease spectrum.

MCR: modern colistin resistance.

Recently, plasmid-mediated and, therefore, transferable bacterial polymyxin resistance was discovered in strains from both humans and animals. Such a trait may widely spread geographically, while simultaneously crossing microbial species barriers. This may ultimately render the "last resort" polymyxin antibiotics therapeutically useless. Colistin is currently used to treat infections caused by Gram-negative carbapenemase producers and colistin resistance may lead to practical pan-antibiotic resistance. We here analyzed the medical and diagnostic consequences of (emerging) colistin resistance and propose pathways toward adequate diagnostics for timely detection of both asymptomatic carriage and infection. Culture-based testing using chromogenic and selective media for screening clinical (and veterinary) specimens may constitute key tools for that purpose. Relevant molecular tests are also discussed.

Immunomodulating properties of protein hydrolysates for application in cow's milk allergy.

Cow's milk proteins cause allergic symptoms in 2-3% of all infants. In these individuals, the tolerogenic state of the intestinal immune system is broken, which can lead to sensitization against antigens and eventually to allergic responses. Although a true treatment for food allergy is not available, symptoms can be avoided by providing the infants with hydrolyzed proteins. Hydrolyzed proteins are proteins that are enzymatically degraded. They lack typical allergenic IgE-binding epitopes but are also thought to play a pertinent role in other mechanisms inducing hypoallergenic effects. This review discusses the mechanisms and evidence for immunomodulating properties of cow's milk hydrolysates. Hydrolysates are found to strengthen the epithelial barrier, modulate T-cell differentiation, and decrease inflammation. Some studies suggest a role for hydrolysates in manipulating pathogen recognition receptors signaling as underlying mechanism. Peptides from hydrolysates have been shown to bind to TLR2 and TLR4 and influence cytokine production in epithelial cells and macrophages. Current insight suggests that hydrolysates may actively participate in modulating the immune responses in subjects with cow's milk allergy and those at risk to develop cow's milk allergy. However, more research is required to design effective and reproducible means to develop targeting strategies to modulate the immune response.

Seasonal distribution of pharmaceuticals in marine water and sediment from a Mediterranean coastal lagoon (SE Spain).

The seasonal variations in the occurrence and distribution of pharmaceuticals were evaluated in seawater and sediment of Mar Menor lagoon from spring 2010 to winter 2011. A total of 20 pharmaceuticals in seawater and 14 in sediments were found at concentrations from low ngL(-)(1) up to 168ngL(-)(1) (azithromycin) in seawater and from low ngg(-1) up to 50.3ngg(-1) (xylazine) in sediments. Azithromycin, xylazine and metoprolol were the most ubiquitous compounds in seawater since they were found in all seawater samples collected. Seven compounds were quantified in both matrices: clarithromycin, erythromycin, hydrochlorothiazide, irbesartan, losartan, salicylic acid and valsartan. Seasonal distribution profiles revealed different sources of pollutants associated to both, El Albujón watercourse (which receives the input of a WWTP) and other non-controlled discharges, into the lagoon. In summer the highest concentrations in seawater for most of the pharmaceuticals were detected close to main touristic nuclei, probably as consequence of sources such as the excretion from bathers and/or other non-controlled discharges, these being significantly higher than in autumn and winter for antibiotics. On the contrary, the mean concentration of lorazepam was significantly higher in colder seasons than in warmer ones. Sulfamethoxazole, erythromycin and especially clarithromycin showed hazard quotients higher than 1 in seawater at some areas of this lagoon indicating a potential risk to aquatic organisms in such specific areas.

Characterization of scrubber water discharges from ships using comprehensive suspect screening strategies based on GC-APCI-HRMS.

An extended suspect screening approach for the comprehensive chemical characterization of scrubber discharge waters from exhaust gas cleaning systems (EGCSs), used to reduce atmospheric shipping emissions of sulphur oxides, was developed. The suspect screening was based on gas chromatography coupled with high-resolution mass spectrometry (GC-HRMS) and focused on the identification of polycyclic aromatic hydrocarbons (PAHs) and their alkylated derivatives (alkyl-PAHs), which are among the most frequent and potentially toxic organic contaminants detected in these matrices. Although alkyl-PAHs can be even more abundant than parent compounds, information regarding their occurrence in scrubber waters is scarce. For compound identification, an in-house compound database was built, with 26 suspect groups, including 25 parent PAHs and 23 alkyl-PAH homologues. With this approach, 7 PAHs and 12 clusters of alkyl-PAHs were tentatively identified, whose occurrence was finally confirmed by target analysis using GC coupled with tandem mass spectrometry (GC-MS/MS). Finally, a retrospective analysis was performed to identify other relevant (poly)cyclic aromatic compounds (PACs) of potential concern in scrubber waters. According to it, 18 suspect groups were tentatively identified, including biphenyls, dibenzofurans, dibenzothiophenes and oxygenated PAHs derivatives. All these compounds could be used as relevant markers of scrubber water contamination in heavy traffic marine areas and be considered as potential stressors when evaluating scrubber water toxicity.

Anaerobic treatment of swine manure under mesophilic and thermophilic temperatures: Fate of veterinary drugs and resistance genes.

The effect of anaerobic treatment of swine manure at 35 °C (mesophilic) and 55 °C (thermophilic) on methane production, microbial community and contaminants of emerging concern was investigated. Pasteurization pretreatment and post treatment was also investigated in combination with anaerobic treatment at 35 °C. Specific methane production (SMP), 26 pharmaceutical compounds (PhACs) and five antibiotic resistance genes (ARGs) (qnrS, tetW, ermB, sul1 and blaTEM) were evaluated. Mesophilic treatment resulted in the highest SMP regardless of whether pasteurization was applied. Marbofloxacin was the most abundant antibiotic in swine manure. In general, all groups of PhACs showed higher removals under thermophilic temperatures as compared to mesophilic. In general, pasteurization pretreatment followed by mesophilic anaerobic digestion provided the highest removals of ARGs. Finally, the genera Streptococcus, Clostridium and Pseudomonas which contain pathogenic species, were present in the swine manure. Streptococcus, which was the most abundant, was decreased during all the treatments, while the others only decreased under certain treatments.

High-salt diet and hypertension: focus on the renin-angiotensin system.

A high-salt diet is one of the major risk factors in the development and maintenance of hypertension. Numerous experimental and observational studies have confirmed the association of sodium intake with blood pressure levels. The effects of a high-salt diet are related to the function of the renin-angiotensin system, which is normally suppressed by a high-salt diet. Endothelial dysfunction probably plays an important role in the influence of high sodium intake on blood pressure, although the exact mechanisms remain elusive. Genetic factors are known to be very important, and various consomic and congenic rat strains as animal models have proven to be very useful in bringing us a step closer to understanding the interaction between salt intake and hypertension. In this article, experimental data obtained in studies on animals and humans, as well as epidemiological data are reviewed.

Assessing the occurrence of pharmaceuticals and antibiotic resistance genes during the anaerobic treatment of slaughterhouse wastewater at different temperatures.

This study investigates the effect of psychrophilic, mesophilic and thermophilic temperatures on the anaerobic treatment of slaughterhouse wastewater, in terms of biogas production, occurrence of 30 pharmaceutical compounds of veterinary use, 4 antibiotic resistance genes (ARGs) which provide resistance to tetracyclines (tetW), fluoroquinolones (qnrS), macrolide-lincosamide-streptogramin (ermB) and sulfonamides (sul1) antibiotics, as well as class I integron-integrase gene (intI1), related to horizontal gene transfer. The highest methane yield was obtained at a mesophilic temperature (35 °C) (323 mL CH4/g TCOD) followed by the yield obtained at thermophilic temperature (53 °C) (242 mL CH4/g TCOD). Regarding pharmaceuticals, chlortetracycline, oxytetracycline, tilmicosin, and lincomycin were the most abundant in the slaughterhouse wastewater, being detected predominantly in the solid phase (with median concentrations >200 µg/kg dry weight). On the other hand, ciprofloxacin, ofloxacin, norfloxacin, lincomycin and ibuprofen were the most predominant in the anaerobic digestate regardless of the treatment temperature. Psychrophilic temperatures (21 °C) exhibited moderate to low pharmaceuticals removal, while a large fraction of them were removed at a thermophilic temperature reaching 70-90% removals for tetracycline, macrolides and one sulfonamide (sulfapyridine). The highest relative abundance of the quantified ARGs was found at 53 °C, suggesting that thermophilic temperatures normally associated with better removals of pathogens do not necessarily show better removals of antibiotic resistance genes.

Change of a catalytic reaction carried out by a DNA replication protein.

The RepA protein of plasmid pC194 initiates and terminates rolling circle replication. At initiation, it forms a 5'-phosphotyrosyl DNA link, whereas at termination, a glutamate residue directs hydrolytic cleavage of the newly synthesized origin, and the resulting 3'-hydroxyl group undergoes transesterification with the phosphotyrosine link. The protein is thus released from DNA, and the termination is uncoupled from reinitiation of replication. Replacement of the glutamate with tyrosine in RepA altered this mechanism, so that termination occurred by two successive transesterifications and became coupled to reinitiation. This result suggests that various enzymes involved in DNA cleavage and rejoining may have similar mechanistic and evolutionary roots.

High-aperture cryogenic light microscopy.

We report here the development of instruments and protocols for carrying out high numerical aperture immersion light microscopy on cryogenic specimens. Imaging by this modality greatly increases the lifetimes of fluorescence probes, including those commonly used for protein localization studies, while retaining the ability to image the specimen with high fidelity and spatial resolution. The novel use of a cryogenic immersion fluid also minimizes the refractive index mismatch between the sample and lens, leading to a more efficient coupling of the light from the sample to the image forming system. This enhancement is applicable to both fluorescence and transmitted light microscopy techniques. The design concepts used for the cryogenic microscope can be applied to virtually any existing light-based microscopy technique. This prospect is particularly exciting in the context of 'super-resolution' techniques, where enhanced fluorescence lifetime probes are especially useful. Thus, using this new modality it is now possible to observe dynamic events in a live cell, and then rapidly vitrify the specimen at a specific time point prior to carrying out high-resolution imaging. The techniques described can be used in conjunction with other imaging modalities in correlated studies. We have also developed instrumentation to perform cryo-light imaging together with soft X-ray tomography on the same cryo-fixed specimen as a means of carrying out high content, quantifiable correlated imaging analyses. These methods are equally applicable to correlated light and electron microscopy of frozen biological objects.

Towards the understanding of antibiotic occurrence and transport in groundwater: Findings from the Baix Fluvià alluvial aquifer (NE Catalonia, Spain).

Antibiotics are an increasing focus of interest due to their high detection frequency in the environment. However, their presence in water bodies is not regulated by environmental policies. This field study investigates, for the first time, the occurrence, behavior and fate of a selection of 53 antibiotics, including up to 10 chemical groups, in an alluvial aquifer originated from manure application in an agricultural region using hydrogeological, hydrochemical and isotopic approaches. Up to 11 antibiotics were found in groundwater corresponding to 4 different chemical groups: fluoroquinolones, macrolides, quinolones and sulfonamides. In surface water, only 5 different antibiotics from 2 chemical groups: fluoroquinolones and sulfonamides, were quantified. The most frequent antibiotics were sulfamethoxazole and ciprofloxacin. Concentrations of antibiotics were in the order of ng/L, with maximum concentrations of 300ng/L in groundwater. Hydrochemistry and isotopic data and geostatistics confirmed the spatial trend observed for nitrates, where nitrate concentrations tend to be higher in the margin areas of the study area, and lower concentrations are found nearby the river. On the other hand, no clear continuous spatial concentration trend of antibiotics was observed in the aquifer, supported by the short spatial correlation found in the variograms. This indicates that the physical-chemical properties and processes of each antibiotic (mainly, sorption and degradation), and other environmental issues, such as a patchy diffuse input and the manure antibiotic content itself, play an important role in their spatial distribution in groundwater. A discussion on the estimation of the antibiotic sorption parameter reveals the difficulties of describing such phenomena. Furthermore, retardation factors will extend over several orders of magnitude, which highly affects the movement of individual antibiotics within the aquifer. To summarize, this study points out the difficulties associated with antibiotic research in groundwater in order to define water resources quality management strategies and environmental regulations.

Development of 100 Mo -containing scintillating bolometers for a high-sensitivity neutrinoless double-beta decay search.

This paper reports on the development of a technology involving 100 Mo -enriched scintillating bolometers, compatible with the goals of CUPID, a proposed next-generation bolometric experiment to search for neutrinoless double-beta decay. Large mass ( ∼ 1 kg ), high optical quality, radiopure 100 Mo -containing zinc and lithium molybdate crystals have been produced and used to develop high performance single detector modules based on 0.2-0.4 kg scintillating bolometers. In particular, the energy resolution of the lithium molybdate detectors near the Q-value of the double-beta transition of 100 Mo (3034 keV) is 4-6 keV FWHM. The rejection of the α -induced dominant background above 2.6 MeV is better than 8 σ . Less than 10 µ Bq/kg activity of 232 Th ( 228 Th ) and 226 Ra in the crystals is ensured by boule recrystallization. The potential of 100 Mo -enriched scintillating bolometers to perform high sensitivity double-beta decay searches has been demonstrated with only 10 kg × d exposure: the two neutrino double-beta decay half-life of 100 Mo has been measured with the up-to-date highest accuracy as T 1 / 2 = [6.90 ± 0.15(stat.) ± 0.37(syst.)] × 10 18 years . Both crystallization and detector technologies favor lithium molybdate, which has been selected for the ongoing construction of the CUPID-0/Mo demonstrator, containing several kg of 100 Mo .

Low pH induced shape changes and vesiculation of human erythrocytes.

Shape changes and vesiculation were induced in intact human erythrocytes by gradually decreasing pH in the cell suspension. A sequence of different shapes preceding vesiculation was documented, i.e. discocytes, stomatocytes, and stomatoacantocytes. The final state was characterized by spherical mother cells and vesicles released. Low pH-induced vesiculation was also studied in the presence of stomatocytogenic or echinocytogenic compounds. The action of stomatocytogenic compounds was inhibitory, and echinocytogenic compounds had no effect on low pH-induced vesiculation. Vesiculation induced by low pH was studied also in isotonic solutions of different sucrose/salt composition. It was concluded that (i) low intracellular pH is responsible for cell shape transformations as well as for release of vesicles, (ii) at temperature 37 degrees C the intracellular pH value which induces the release of vesicles is 5.4, and (iii) the sequence of typical shape changes preceding vesiculation does not include echinocytes. The results are discussed on the basis of the layered membrane model of the shape formation and shape transformations of the human erythrocyte, and additionally considering the partial detachment of the membrane skeleton from the bilayer part of the membrane.

[Complex partial seizures: the localization value of automatisms]. / Crisis parciales complejas: valor localizador de los automatismos.

INTRODUCTION: The clinical findings in complex partial crises may help our understanding of the different foci and vias of epileptogenesis. MATERIAL AND METHODS: We analyse automatisms and findings on EEG and neuroimaging in 151 patients with different types of partial epilepsy, seeking to establish a possible correlation between the type of automatism and cerebral localization. RESULTS AND CONCLUSIONS: The relative frequency of automatisms was: oro-alimentary 30%, mimicking 11%, gestures 35%, ambulatory 19% and verbal 13%. There was a statistically significant difference between the type of automatism and the topography of the EEG and neuroimaging findings. There were more gesture and oro-alimentary automatisms in patients with temporal anomalies, both on EEG and on neuroimaging, than in those with extratemporal alterations.

[Prognostic value of data from clinical, EEG and neuroimaging assessment in epilepsy with complex partial seizures]. / Valor pronóstico de los datos clínicos, EEG y neuroimagen en la epilepsia con crisis parciales complejas.

INTRODUCTION: The well-known etiology, length of active epilepsy, partial or mixed seizure types and high frequency of seizures before treatment relate with a worst prognosis for seizures control. We have attempted to prove these factors in our study. METHOD: We analyzed the electro-clinical characteristics, evolution and etiology of seizures in 151 patient with several type of partial epilepsy. Subsequently, we related the estimated improvement with diverse variables. RESULTS: A significant statistically difference appeared as for seizures frequency at onset, existing among 15% to 44.3% more patient in which the frequency descended to more of 50% when the initial frequency was more than one to the month. Upon relating the improvement with the MR anomaly also appeared significant difference: there was between 7.9% and 73.7% more patient with hypersignal on long TR sequences in the group that did not decrease the frequency of their crisis to more than 50%.

[Multiple sclerosis as a cause of partial complex epilepsy]. / Esclerosis múltiple como causa de crisis parciales complejas.

INTRODUCTION: Although the epileptic seizures (ES) have been described on patients with multiple sclerosis (MS), the causal relationship is not clear. Seizure's prevalence in this illness is low and their apparition concerning the MS course is variable, but more common after MS diagnosis. The predominant crises are generalized or partial with secondary generalization; the partial complex seizures have rarely referred. CLINICAL CASES AND CONCLUSIONS: We presented two patients with ES in the MS course. In the first case is arrived to MS diagnosis upon appearing the crisis, having presented two previous cerebral lesions in another level. In both cases demyelinating lesion was located in the temporal lobe, agreeing with EEG anomaly and seizures type.

Input of pharmaceuticals through coastal surface watercourses into a Mediterranean lagoon (Mar Menor, SE Spain): sources and seasonal variations.

The seasonal occurrence and distribution of 69 pharmaceuticals along coastal watercourses during 6 sampling campaigns and their input through El Albujón watercourse to the Mar Menor lagoon were determined by UPLC-MS-MS, considering a total of 115 water samples. The major source of pharmaceuticals running into this watercourse was an effluent from the Los Alcazares WWTP, although other sources were also present (runoffs, excess water from irrigation, etc.). In this urban and agriculturally influenced watercourse different pharmaceutical distribution profiles were detected according to their attenuation, which depended on physicochemical water conditions, pollutant input variation, biodegradation and photodegradation rates of pollutants, etc. The less recalcitrant compounds in this study (macrolides, ß-blockers, etc.) showed a relevant seasonal variability as a consequence of dissipation processes (degradation, sorption, etc.). Attenuation was lower, however, for diclofenac, carbamazepine, lorazepam, valsartan, sulfamethoxazole among others, due to their known lower degradability and sorption onto particulate matter, according to previous studies. The maximum concentrations detected were higher than 1000 ng L(-1) for azithromycin, clarithromycin, valsartan, acetaminophen and ibuprofen. These high concentration levels were favored by the limited dilution in this low flow system, and consequently some of them could pose an acute risk to the biota of this watercourse. Considering data from 2009 to 2010, it has been estimated that a total of 11.3 kg of pharmaceuticals access the Mar Menor lagoon annually through the El Albujón watercourse. The highest proportion of this input corresponded to antibiotics (46%), followed by antihypertensives (20%) and diuretics (18%).