189 research outputs found
Occupational, domestic and environmental mesothelioma risks in the British population: a caseâcontrol study
We obtained lifetime occupational and residential histories by telephone interview with 622 mesothelioma patients (512 men, 110 women) and 1420 population controls. Odds ratios (ORs) were converted to lifetime risk (LR) estimates for Britons born in the 1940s. Male ORs (95% confidence interval (CI)) relative to low-risk occupations for >10 years of exposure before the age of 30 years were 50.0 (25.8â96.8) for carpenters (LR 1 in 17), 17.1 (10.3â28.3) for plumbers, electricians and painters, 7.0 (3.2â15.2) for other construction workers, 15.3 (9.0â26.2) for other recognised high-risk occupations and 5.2 (3.1â8.5) in other industries where asbestos may be encountered. The LR was similar in apparently unexposed men and women (âŒ1 in 1000), and this was approximately doubled in exposed workers' relatives (OR 2.0, 95% CI 1.3â3.2). No other environmental hazards were identified. In all, 14% of male and 62% of female cases were not attributable to occupational or domestic asbestos exposure. Approximately half of the male cases were construction workers, and only four had worked for more than 5 years in asbestos product manufacture
The Extracellular Matrix Component Psl Provides Fast-Acting Antibiotic Defense in Pseudomonas aeruginosa Biofilms
Bacteria within biofilms secrete and surround themselves with an extracellular matrix, which serves as a first line of defense against antibiotic attack. Polysaccharides constitute major elements of the biofilm matrix and are implied in surface adhesion and biofilm organization, but their contributions to the resistance properties of biofilms remain largely elusive. Using a combination of static and continuous-flow biofilm experiments we show that Psl, one major polysaccharide in the Pseudomonas aeruginosa biofilm matrix, provides a generic first line of defense toward antibiotics with diverse biochemical properties during the initial stages of biofilm development. Furthermore, we show with mixed-strain experiments that antibiotic-sensitive ânon-producingâ cells lacking Psl can gain tolerance by integrating into Psl-containing biofilms. However, non-producers dilute the protective capacity of the matrix and hence, excessive incorporation can result in the collapse of resistance of the entire community. Our data also reveal that Psl mediated protection is extendible to E. coli and S. aureus in co-culture biofilms. Together, our study shows that Psl represents a critical first bottleneck to the antibiotic attack of a biofilm community early in biofilm development.National Institutes of Health (U.S.). National Institute of Environmental Health Sciences (Training Grant in Toxicology 5 T32 ES7020-37
Patients' experiences of living with and receiving treatment for fibromyalgia syndrome: a qualitative study
<p>Abstract</p> <p>Background</p> <p>Fibromyalgia syndrome (FMS) presents a challenge for patients and health care staff across many medical specialities. The aetiology is multi-dimensional, involving somatic, psychological and social factors. Patients' views were obtained to understand their experience of living with this long-term condition, using qualitative interviews.</p> <p>Methods</p> <p>12 patients were recruited and stratified by age, gender and ethnicity from one rheumatology outpatient clinic, and a departmental held database of patients diagnosed with FMS.</p> <p>Results</p> <p>Patients' accounts of their experience of FMS resonated well with two central concepts: social identity and illness intrusiveness. These suggested three themes for the analytical framework: life before and after diagnosis (e.g. lack of information about FMS, invisibility of FMS); change in health identity (e.g. mental distress, impact on social life) and perceived quality of care (e.g. lack of contact with nurses, attitudes of specialists). The information provided from one male participant did not differ from the female patients, but black and ethnic community patients expressed a degree of suspicion towards the medication prescribed, and the attitudes displayed by some doctors, a finding that has not been previously reported amongst this patient group. Patients expected more consultation time and effective treatment than they received. Subjective experiences and objective physical and emotional changes were non-overlapping. Patients' accounts revealed that their physical, mental and social health was compromised, at times overwhelming and affected their identity.</p> <p>Conclusion</p> <p>FMS is a condition that intrudes upon many aspects of patients' lives and is little understood. At the same time, it is a syndrome that evokes uneasiness in health care staff (as current diagnostic criteria are not well supported by objective markers of physiological or biochemical nature, and indeed because of doubt about the existence of the condition) and places great demands on resources in clinical practice. Greater attention needs to be paid to the links between the explanatory models of patients and staff, and most important, to the interrelationship between the complex physical, psychological and social needs of patients with FMS. Taking a less medical but more holistic approach when drawing up new diagnostic criteria for FMS might match better individuals' somatic and psycho-social symptom profile and may result in more effective treatment.</p
Molecular mechanisms and cellular functions of cGAS-STING signalling
The cGASâSTING signalling axis, comprising the synthase for the second messenger cyclic GMPâAMP (cGAS) and the cyclic GMPâAMP receptor stimulator of interferon genes (STING), detects pathogenic DNA to trigger an innate immune reaction involving a strong type I interferon response against microbial infections. Notably however, besides sensing microbial DNA, the DNA sensor cGAS can also be activated by endogenous DNA, including extranuclear chromatin resulting from genotoxic stress and DNA released from mitochondria, placing cGASâSTING as an important axis in autoimmunity, sterile inflammatory responses and cellular senescence. Initial models assumed that co-localization of cGAS and DNA in the cytosol defines the specificity of the pathway for non-self, but recent work revealed that cGAS is also present in the nucleus and at the plasma membrane, and such subcellular compartmentalization was linked to signalling specificity of cGAS. Further confounding the simple view of cGASâSTING signalling as a response mechanism to infectious agents, both cGAS and STING were shown to have additional functions, independent of interferon response. These involve non-catalytic roles of cGAS in regulating DNA repair and signalling via STING to NF-ÎșB and MAPK as well as STING-mediated induction of autophagy and lysosome- dependent cell death. We have also learnt that cGAS dimers can multimerize and undergo liquidâliquid phase separation to form biomolecular condensates that could importantly regulate cGAS activation. Here, we review the molecular mechanisms and cellular functions underlying cGASâSTING activation and signalling, particularly highlighting the newly emerging diversity of this signalling pathway and discussing how the specificity towards normal, damage-induced and infection-associated DNA could be achieved
Test of lepton universality in decays
The first simultaneous test of muon-electron universality using
and decays is performed, in two ranges of the dilepton
invariant-mass squared, . The analysis uses beauty mesons produced in
proton-proton collisions collected with the LHCb detector between 2011 and
2018, corresponding to an integrated luminosity of 9 . Each
of the four lepton universality measurements reported is either the first in
the given interval or supersedes previous LHCb measurements. The
results are compatible with the predictions of the Standard Model.Comment: All figures and tables, along with any supplementary material and
additional information, are available at
https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2022-046.html (LHCb
public pages
Precision measurement of violation in the penguin-mediated decay
A flavor-tagged time-dependent angular analysis of the decay
is performed using collision data collected
by the LHCb experiment at % at TeV, the center-of-mass energy of
13 TeV, corresponding to an integrated luminosity of 6 fb^{-1}. The
-violating phase and direct -violation parameter are measured
to be rad and
, respectively, assuming the same values
for all polarization states of the system. In these results, the
first uncertainties are statistical and the second systematic. These parameters
are also determined separately for each polarization state, showing no evidence
for polarization dependence. The results are combined with previous LHCb
measurements using collisions at center-of-mass energies of 7 and 8 TeV,
yielding rad and . This is the most precise study of time-dependent violation
in a penguin-dominated meson decay. The results are consistent with
symmetry and with the Standard Model predictions.Comment: All figures and tables, along with any supplementary material and
additional information, are available at
https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2023-001.html (LHCb
public pages
Observation of a resonant structure near the threshold in the decay
An amplitude analysis of the decay is carried out to
study for the first time its intermediate resonant contributions, using
proton-proton collision data collected with the LHCb detector at centre-of-mass
energies of 7, 8 and 13 TeV. A near-threshold peaking structure, referred to as
, is observed in the invariant-mass spectrum with
significance greater than 12 standard deviations. The mass, width and the
quantum numbers of the structure are measured to be MeV,
MeV and , respectively, where the first
uncertainties are statistical and the second systematic. The properties of the
new structure are consistent with recent theoretical predictions for a state
composed of quarks. Evidence for an additional structure is
found around 4140 MeV in the invariant mass, which might be
caused either by a new resonance with the assignment or by a coupled-channel effect.Comment: All figures and tables, along with any supplementary material and
additional information, are available at
https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2022-018.html (LHCb
public pages
Measurement of the differential branching fraction
The branching fraction of the rare decay is measured for the first time, in the squared dimuon mass
intervals, , excluding the and regions. The data
sample analyzed was collected by the LHCb experiment at center-of-mass energies
of 7, 8, and 13 TeV, corresponding to a total integrated luminosity of $9\
\mathrm{fb}^{-1}q^{2}q^{2} >15.0\
\mathrm{GeV}^2/c^4$, where theoretical predictions have the smallest model
dependence, agrees with the predictions.Comment: All figures and tables, along with any supplementary material and
additional information, are available at
https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2022-050.html (LHCb
public pages
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