In Casares et al. we presented the first radial velocity curve of the companion star to BW Cir which demonstrates the presence of a black hole in this historical X-ray transient. But these data were ...affected by aliasing and two possible periods at 2.5445 days and 2.5635 days were equally possible. Here we present new spectroscopic data that enable us to break the 1-year aliasing and confirm 2.5445 days as the correct orbital period. We also present R-band photometry over 14 years, which reveals the presence of important flaring activity dominating the light curves.
This paper presents the techniques used to monitor radiation damage in the LHCb Tracker Turicensis during the LHC Runs 1 and 2. Bulk leakage currents in the silicon sensors were monitored ...continuously, while the full depletion voltages of the sensors were estimated at regular intervals by performing dedicated scans of the charge collection efficiency as a function of the applied bias voltage. Predictions of the expected leakage currents and full depletion voltages are extracted from the simulated radiation profile, the luminosity delivered by the LHC, and the thermal history of the silicon sensors. Good agreement between measurements and predictions is found.
Cationic liposomes have been extensively studied from the experimental and theoretical standpoints, motivated both by their fundamental interest and by potential applications in drug delivery and ...gene therapy. However, a detailed understanding of the nature of interactions within mixed bilayers containing cationic gemini surfactants is still lacking. This work focuses on the structural and dynamic properties of DODAB membranes in the presence of dicationic gemini surfactants. A thermodynamic characterization of the phase transitions in the mixed systems has been carried out by differential scanning calorimetry, while insight into the molecular interactions in the bilayer has been provided by molecular dynamics. For this purpose, variations in the gemini spacer and tail length, as well as in the respective molar fraction, have been included in both experimental and simulation studies. The results indicate that the influence of cationic gemini surfactants upon the thermotropic behavior and degree of order of DODAB structures is controlled by a complex interplay between charge density, conformation and hydrophobic effects, for which a detailed rationale is provided.
Background and importanceUncertainty exists regarding the comparative effectiveness of cetuximab versus bevacizumab in metastatic colorectal cancer (mCRC) due to conflicting evidence of efficacy of ...previous randomised clinical trials and the absence of quality of life (HRQoL) studies in this setting.Aim and objectivesIn order to assess clinical effectiveness and patient reported tolerability of the different targeted treatment options simultaneously, we conducted a mainly retrospective head-to-head multi-cohort study. The main retrospective study was designed to compare real world clinical outcomes from both antibodies. Concurrently, we nested in it a smaller prospective cohort study for the purpose of measuring patient reported outcomes (PROs).Material and methodsRetrospective cohorts were defined by treatment line, and subgroups by (K)RAS status and tumour sidedness. Among other effectiveness outcomes, we compared response rates, progression free survival (PFS) and overall survival (OS). PROs were measured prospectively through EORTC disease specific instruments. Methods and reporting followed STROBE guidelines and SISAQOL/SPIRIT-PRO recommendations.ResultsBetween 2010 and 2018, 311 mCRC patients were included in the overall analysis, of whom 44 were further allocated to PROs nested cohorts. Except for (K)RAS mutation status, baseline characteristics were balanced across groups. In the full analyses, PFS (firstline: HR=0.85; p=0.26; secondline: HR=1.16; p=0.51) and OS (firstline: HR=0.83; p=0.26; secondline: HR=0.88; p=0.58) were similar between treatment arms. In subgroup analyses (firstline), we found a survival difference favouring bevacizumab in right-sided tumours (PFS: HR=0.52; p=0.025; OS: HR=0.60; p=0.11), but not in left-sided or (K)RAS wild-type tumours. Response rates were higher for bevacizumab in patients with right-sided primaries and similar across other comparisons. During the first 12 weeks of treatment, a higher proportion of patients in the cetuximab arm experienced clinically meaningful (≥10%) deterioration of HRQoL comparing with the bevacizumab cohort: 53.8% versus 18.2% at 6 weeks and 66.7% versus 12.5% at 12 weeks. We also observed progressively increased scoring on the symptom scales in the cetuximab cohort during follow-up.Conclusion and relevanceThis study provides evidence suggesting that bevacizumab and cetuximab containing regimens result in similar clinical effectiveness outcomes in mCRC, except for right-sided tumours, where bevacizumab performed substantially better. Cetuximab led to a progressive negative impact on HRQoL compared with baseline and bevacizumab. These findings should be further explored in randomised studies.References and/or acknowledgementsConflict of interestNo conflict of interest
South Asians who have settled overseas and those in urban India have an increased risk of ischaemic heart disease (IHD). Reasons for this increased risk are unclear. Most studies have been based on ...migrants to western nations, so their findings may not apply to most south Asians, who live in their own countries. Therefore, we assessed the relative importance of risk factors for IHD among South Asians in Bangalore, India.
We conducted a prospective hospital-based case-control study of 200 Indian patients with a first acute myocardial infarction (AMI) and 200 age and sex matched controls. We recorded prevalence of the following risk factors for IHD: diet, smoking, alcohol use, socioeconomic status, waist to hip ratio (WHR), blood glucose, serum insulin, oral glucose tolerance test, and lipid profile.
The most important predictor of AMI was current smoking (odds ratio OR 3·6, p < 0·001) of cigarettes or beedis (a local form of tobacco), with individuals who currently smoked 10 or more per day having an OR of 6·7 (p < 0·001). History of hypertension and of overt diabetes mellitus were also independent risk factors (OR 2·69 p=0·001 and 2·64 p=0·004, respectively). Among all individuals, fasting blood glucose was a strong predictor of risk over the entire range, including at values usually regarded as normal (OR adjusted for smoking, hypertension, and WHR 1·62 for 1 SD increase, p < 0·001). Abdominal obesity (as measured by WHR) was also a strong independent predictor across the entire range of measures (OR adjusted for smoking, hypertension, and blood glucose 2·24 for 1 SD increase; p < 0·001). Compared with individuals with no risk factors, individuals with multiple risk factors had greatly increased risk of AMI (eg, OR of 10·6 for the group with smoking and elevated glucose). Lipid profile was not associated with AMI. In univariate analyses, higher socioeconomic (income) status (OR 0·32, p=0·005 highest
vs lowest; OR 0·75 middle
vs lowest) and vegetarianism (OR=0·55, p=0·006), seemed to be protective. The impact of vegetarianism was closely correlated with blood glucose and WHR.
Smoking cessation, treatment of hypertension, and reduction in blood glucose and central obesity (perhaps through dietary modification) may be important in preventing IHD in Asian Indians.
Abstract Fukuyama congenital muscular dystrophy (FCMD) is one of the most common autosomal recessive diseases among the Japanese population, due to a founder mutation of the fukutin gene ( FKTN ). ...Mutations in FKTN are now being described in an increasing number of non-Japanese patients. We report a Portuguese child with FCMD. The diagnosis was supported by clinical, histological, magnetic resonance imaging (MRI) and genetic studies. Genetic analysis of FKTN by Multiplex Ligation Probe Amplification (MLPA) revealed a homozygous duplication from exon 4 to exon 7. This in-frame duplication was confirmed by cDNA analysis. To our knowledge this is the first report of a FCMD case caused by an intragenic gross exonic duplication in the FKTN gene. This report widens the clinical and mutational spectrum in FCMD and corroborates the importance of screening for large deletions and duplications in CMD patients.
Glutaric aciduria type 1 is an autosomal recessive disorder caused by deficiency of glutaryl-coenzyme A dehydrogenase, with accumulation of glutaric acid, 3-hydroxyglutaric acid and glutaconic acid. ...Increased blood glutarylcarnitine levels are the basis for identification of affected infants by newborn screening. Despite the highly variability, this disease usually presents with an acute encephalitis-like encephalopathy in infancy or childhood after a period of normal development. The characteristic neurological sequel is a complex movement disorder due to acute bilateral striatal injury. Frequently, the only abnormality preceding the first episode is a progressive macrocephaly. Although neuroimaging findings are quite variable, the widening of the Sylvian fissures combined with abnormalities of the basal ganglia in a child with macrocephaly should raise the suspicion of this diagnosis. We describe two patients in whom macrocephaly was the only presenting symptom and whose diagnosis was suggested by the brain MRI findings. Our purpose is to illustrate the clinical value of neuroimaging in the diagnosis of glutaric aciduria type 1 even before the onset of neurologic symptoms, which is particularly important if newborn screening is not available.
Key Clinical Message
The clinical recognition of CSF fistula is a clinical challenge. We report the case of a young woman, who presented with a late orthostatic headache 20 months after epidural ...anesthesia. She developed a lumbar dural fistula of CSF confirmed in myelography CT scanning and treated successfully with epidural blood patch.
The clinical recognition of CSF fistula is a clinical challenge. We report the case of a young woman, who presented with a late orthostatic headache 20 months after epidural anesthesia. She developed a lumbar dural fistula of CSF confirmed in myelography CT scanning and treated successfully with epidural blood patch.
The decays
Λ
b
0
→
Λ
c
+
D
¯
(
∗
)
0
K
-
and
Λ
b
0
→
Λ
c
+
D
s
∗
-
are observed for the first time, in proton-proton collision data at
s
=
13
Te
V
, corresponding to an integrated luminosity of 5.4
...fb
-
1
collected with the LHCb detector. Their ratios of branching fractions with respect to the
Λ
b
0
→
Λ
c
+
D
s
-
mode are measured to be
B
Λ
b
0
→
Λ
c
+
D
¯
0
K
-
B
Λ
b
0
→
Λ
c
+
D
s
-
=
0.1908
-
0.0034
+
0.0036
-
0.0018
+
0.0016
±
0.0038
,
B
Λ
b
0
→
Λ
c
+
D
¯
∗
0
K
-
B
Λ
b
0
→
Λ
c
+
D
s
-
=
0.589
-
0.017
+
0.018
-
0.018
+
0.017
±
0.012
,
B
Λ
b
0
→
Λ
c
+
D
s
∗
-
B
Λ
b
0
→
Λ
c
+
D
s
-
=
1.668
±
0.022
-
0.055
+
0.061
,
where the first uncertainties are statistical, the second systematic, and the third, for the
Λ
b
0
→
Λ
c
+
D
¯
(
∗
)
0
K
-
decays, are due to the uncertainties on the branching fractions of the
D
s
-
→
K
-
K
+
π
-
and
D
¯
0
→
K
+
π
-
decay modes. The measured branching fractions probe factorization assumptions in effective theories and provide the normalization for future pentaquark searches in
Λ
b
0
→
Λ
c
+
D
¯
(
∗
)
0
K
-
decay channels.
An important goal of gene therapy is to be able to deliver genes, so that they express in a pattern that recapitulates the expression of an endogenous cellular gene. Although tissue-specific ...promoters confer selectivity, in a vector-based system, their activity may be too weak to mediate detectable levels in gene-expression studies. We have used a two-step transcriptional amplification system to amplify gene expression from lentiviral vectors using the human insulin promoter. In this system, the human insulin promoter drives expression of a potent synthetic transcription activator (the yeast GAL4 DNA-binding domain fused to the activation domain of the Herpes simplex virus-1 VP16 activator), which in turn activates a GAL4-responsive promoter, driving the enhanced green fluorescent protein reporter gene. Vectors carrying the human insulin promoter did not express in non-beta-cell lines, but expressed in murine insulinoma cell lines, indicating that the human insulin promoter was capable of conferring cell specificity of expression. The insulin-amplifiable vector was able to amplify gene expression five to nine times over a standard insulin-promoter vector. In primary human islets, gene expression from the insulin-promoted vectors was coincident with insulin staining. These vectors will be useful in gene-expression studies that require a detectable signal and tissue specificity.
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