Abstract
The CUPID-Mo experiment to search for 0
$$\nu \beta \beta $$
ν
β
β
decay in
$$^{100}$$
100
Mo has been recently completed after about 1.5 years of operation at Laboratoire Souterrain de ...Modane (France). It served as a demonstrator for CUPID, a next generation 0
$$\nu \beta \beta $$
ν
β
β
decay experiment. CUPID-Mo was comprised of 20 enriched
$$\hbox {Li}_{{2}}$$
Li
2
$$^{100}$$
100
$$\hbox {MoO}_4$$
MoO
4
scintillating calorimeters, each with a mass of
$$\sim 0.2$$
∼
0.2
kg, operated at
$$\sim 20$$
∼
20
mK. We present here the final analysis with the full exposure of CUPID-Mo (
$$^{100}$$
100
Mo exposure of 1.47
$$\hbox {kg} \times \hbox {year}$$
kg
×
year
) used to search for lepton number violation via 0
$$\nu \beta \beta $$
ν
β
β
decay. We report on various analysis improvements since the previous result on a subset of data, reprocessing all data with these new techniques. We observe zero events in the region of interest and set a new limit on the
$$^{100}$$
100
Mo 0
$$\nu \beta \beta $$
ν
β
β
decay half-life of
$$T_{1/2}^{0\nu }$$
T
1
/
2
0
ν
$$> {1.8}\times 10^{24}$$
>
1.8
×
10
24
year (stat. + syst.) at 90% CI. Under the light Majorana neutrino exchange mechanism this corresponds to an effective Majorana neutrino mass of
$$\left<m_{\beta \beta }\right>$$
m
β
β
$$<~{(0.28{-}0.49)} $$
<
(
0.28
-
0.49
)
eV, dependent upon the nuclear matrix element utilized.
Neutrinoless double beta decay (0νββ) 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 (2νββ) is allowed by the standard model and has been measured in numerous experiments. In this Letter, we report a measurement of 2νββ decay half-life of 100Mo to the ground state of 100Ru of 7.07±0.02(stat)±0.11(syst)×1018 yr by the CUPID-Mo experiment. With a relative precision of ±1.6% this is the most precise measurement to date of a 2νββ decay rate in 100Mo. 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 ξ3,1=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. Finally, we also extract the first value for the effective axial vector coupling constant obtained from a spectral shape study of 2νββ decay.
The prevalence of mixed dementia, defined as the coexistence of Alzheimer disease (AD) and vascular dementia (VaD), is likely to increase as the population ages.
To provide an overview of the ...diagnosis, pathophysiology, and interaction of AD and VaD in mixed dementia, and to provide a systematic literature review of the current evidence for the pharmacologic therapy of mixed dementia.
The Cochrane Database of Systematic Reviews was searched using the keyword dementia. MEDLINE was searched for English-language articles published within the last 10 years using the keywords mixed dementia, the combination of keywords Alzheimer disease, cerebrovascular disorders, and drug therapy, and the combination of keywords vascular dementia and drug therapy.
Dementia is more likely to be present when vascular and AD lesions coexist, a situation that is especially common with increasing age. The measured benefits in clinical trials for the treatment of mixed dementia are best described as statistically significant differences in cognitive test scores and clinician and caregiver impressions of change. In these studies, the control groups' scores typically decline while the treatment groups improve slightly or decline to a lesser degree over the study period. Nevertheless, even the patients who experience treatment benefits eventually decline. Cholinesterase inhibitor (ChI) therapy for mixed dementia shows modest clinical benefits that are similar to those found for ChI treatment of AD. The N-methyl-D-aspartate (NMDA) antagonist memantine also shows modest clinical benefits for the treatment of moderate to severe AD and mild to moderate VaD, but it has not been studied specifically in mixed dementia. The treatment of cardiovascular risk factors, especially hypertension, may be a more effective way to protect brain function as primary, secondary, and tertiary prevention for mixed dementia.
Currently available medications provide only modest clinical benefits once a patient has developed mixed dementia. Cardiovascular risk factor control, especially for hypertension and hyperlipidemia, as well as other interventions to prevent recurrent stroke, likely represent important strategies for preventing or slowing the progression of mixed dementia. Additional research is needed to define better what individuals and families hope to achieve from dementia treatment and to determine the most appropriate use of medication to achieve these goals.
The CUPID-Mo experiment to search for 0
ν
β
β
decay in
100
Mo has been recently completed after about 1.5 years of operation at Laboratoire Souterrain de Modane (France). It served as a demonstrator ...for CUPID, a next generation 0
ν
β
β
decay experiment. CUPID-Mo was comprised of 20 enriched
Li
2
100
MoO
4
scintillating calorimeters, each with a mass of
∼
0.2
kg, operated at
∼
20
mK. We present here the final analysis with the full exposure of CUPID-Mo (
100
Mo exposure of 1.47
kg
×
year
) used to search for lepton number violation via 0
ν
β
β
decay. We report on various analysis improvements since the previous result on a subset of data, reprocessing all data with these new techniques. We observe zero events in the region of interest and set a new limit on the
100
Mo 0
ν
β
β
decay half-life of
T
1
/
2
0
ν
>
1.8
×
10
24
year (stat. + syst.) at 90% CI. Under the light Majorana neutrino exchange mechanism this corresponds to an effective Majorana neutrino mass of
m
β
β
<
(
0.28
-
0.49
)
eV, dependent upon the nuclear matrix element utilized.
Preterm birth is common in twins and accounts for significant mortality and morbidity. There are no effective preventative treatments. Some studies have suggested that, in twin pregnancy complicated ...by a short cervix, the Arabin pessary, which fits around the cervix and can be inserted as an outpatient procedure, reduces preterm birth and prevents neonatal morbidity.
STOPPIT 2 aimed to evaluate the clinical utility of the Arabin cervical pessary in preventing preterm birth in women with a twin pregnancy and a short cervix.
STOPPIT 2 was a pragmatic, open label, multicentre randomised controlled trial with two treatment group - the Arabin pessary plus standard care (intervention) and standard care alone (control). Participants were initially recruited into the screening phase of the study, when cervical length was measured. Women with a measured cervical length of ≤ 35 mm were then recruited into the treatment phase of the study. An economic evaluation considered cost-effectiveness and a qualitative substudy explored the experiences of participants and clinicians.
Antenatal clinics in the UK and elsewhere in Europe.
Women with twin pregnancy at < 21 weeks' gestation with known chorionicity and gestation established by scan at ≤ 16 weeks' gestation.
Ultrasound scan to establish cervical length. Women with a cervical length of ≤ 35 mm at 18
-20
weeks' gestation were randomised to standard care or Arabin pessary plus standard care. Randomisation was performed by computer and accessed through a web-based browser.
Obstetric - all births before 34
weeks' gestation following the spontaneous onset of labour; and neonatal - composite of adverse outcomes, including stillbirth or neonatal death, periventricular leukomalacia, early respiratory morbidity, intraventricular haemorrhage, necrotising enterocolitis or proven sepsis, all measured up to 28 days after the expected date of delivery.
A total of 2228 participants were recruited to the screening phase, of whom 2170 received a scan and 503 were randomised: 250 to Arabin pessary and 253 to standard care alone. The rate of the primary obstetric outcome was 18.4% (46/250) in the intervention group and 20.6% (52/253) in the control group (adjusted odds ratio 0.87, 95% confidence interval 0.55 to 1.38;
= 0.54). The rate of the primary neonatal outcome was 13.4% (67/500) and 15.0% (76/506) in the intervention group and control group, respectively (adjusted odds ratio 0.86, 95% confidence interval 0.54 to 1.36;
= 0.52). The pessary was largely well tolerated and clinicians found insertion and removal 'easy' or 'fairly easy' in the majority of instances. The simple costs analysis showed that pessary treatment is no more costly than standard care.
There was the possibility of a type II error around smaller than anticipated benefit.
In this study, the Arabin pessary did not reduce preterm birth or adverse neonatal outcomes in women with a twin pregnancy and a short cervix. The pessary either is ineffective at reducing preterm birth or has an effect size of < 0.4.
Women with twin pregnancy remain at risk of preterm birth; work is required to find treatments for this.
Current Controlled Trials ISRCTN98835694 and ClinicalTrials.gov NCT02235181.
This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in
; Vol. 25, No. 44. See the NIHR Journals Library website for further project information.
Ecological thresholds, associated with abrupt changes in the state and organisation of ecosystems, challenge both scientists and managers. Adaptive response to such changes, and planning for their ...occurrence, requires an understanding of the underlying drivers and system responses as well as appropriate monitoring. In addition to field studies, modelling can advance our ability to anticipate or deal with such major ecosystem shifts. Here, we used an existing multispecies model with smooth continuous functions that were modified to include thresholds representing 3 alternative scenarios of predator responses when prey numbers drop below a critical threshold: (I) no threshold-like response; (II) an abrupt decrease in breeding success by 90%, and (III) an abrupt halving of adult survival. Second, we analysed field observations from 3 independent marine case studies (abalone, starfish, penguins) for evidence of abrupt non-linear responses of predators to changes in abundance of principal prey. Third, we compared the model output with empirical results and tested (using both a statistical method and by fitting multispecies models) the 3 alternative response scenarios. With this approach, we found evidence for nonlinear changes in population parameters (such as survival rate) of predators as prey numbers declined below critical thresholds. As an example of the potential for this approach to inform management, we found that abundances of a range of marine predators become more variable as prey numbers decline, which may be a useful indicator that a system is approaching a tipping point.
Changes in the fibroblast growth factor receptor (FGFR) axis are often associated with prostate cancer (CaP) progression. We have used chemically induced dimerization (CID) to elucidate the ...individual contributions of FGFR1 and FGFR2 to tumor etiology. Novel CaP cell lines stably expressing CID/AP20187-inducible FGFR1 (iFGFR1) and iFGFR2 were made using the tumorigenic transgenic adenocarcinoma of the murine prostate (TRAMP)-derived clone, TRAMP-C2N (C2N), to generate C2N.iFGFR1 or C2N.iFGFR2 cells. To test the effects of iFGFR activation on tumor growth, mice bearing s.c. C2N.iFGFR1- or C2N.iFGFR2-derived tumors were treated biweekly with CID. Activation of iFGFR1 led to rapid tumor growth as a result of increased proliferation. In contrast, expression of iFGFR2 inhibited tumor growth. Furthermore, we have ascertained that FGFR1 activation appears to be most important during the early stages of tumor development, but once established, tumors become rapidly CID independent. In these C2N-based lines, quantitative signaling differences were seen between the two receptors, with iFGFR1 leading to more robust extracellular signal-regulated kinase activation. Additionally, activation of iFGFR1, but not iFGFR2, led to strong up-regulation of osteopontin, a secreted glycoprotein involved in integrin activation and associated with CaP progression and metastasis. These studies support the hypothesis that observed changes in the FGFR axis in mammals during CaP progression are causally important.
Accurate determination of the contributions of oncogenes toward tumor progression requires their regulation. Herein, we created transgenic mice with prostate-specific expression of ligand-inducible ...FGFR1 or FGFR2, based on lipid-permeable dimerizing molecules, called chemical inducers of dimerization. Despite extensive homology and equivalent expression by both chimeric receptors in the ventral prostate gland, only FGFR1 triggers detectable nuclear translocation of Erk and progression to prostatic intraepithelial neoplasia (PIN). Induction of PIN grade I-II, indicated by multiple layers of atypical cells, is seen consistently by 12 weeks of chemical inducers of dimerization treatment. By 6 months, more extensive nuclear atypia, thickened "reactive" stroma, and basement membrane herniation occurs, corresponding to PIN IV. By timed removal of FGFR1 signaling, we show that induced hyperplasia is reversible until extensive intraductal vascularization occurs, but continued progression requires prolonged FGFR1 signaling. Additionally, by highlighting differences between the two receptors and creating the foundation for controlling FGFR1 signaling during prostate cancer progression, a model of early stage prostate cancer is established for developing targeted intervention directed toward the FGFR signaling axis.
Background: The experience with 30 years of cardiac transplantation at Stanford University Medical Center was reviewed. A total of 954 transplants were performed in 885 patients. Patients were ...divided into 3 groups based on immunosuppression received: group I, no cyclosporine (INN: ciclosporin) (n = 201) (January 1968–November 1980); group II, cyclosporine (n = 248) (December 1980–June 1987); and group III, cyclosporine + OKT3 (n = 436) (July 1987–March 1998).
Results:The 1-, 5-, and 10-year actuarial survivals were 68%, 41%, and 24% (group I); 80%, 57%, and 37% (group II); and 85%, 68%, and 46% (group III) (I vs II,
P < .01; I vs III,
P < .005; and II vs III,
P < .005). The 1-, 5-, and 10-year actuarial death rates from rejection were 8%, 12%, and 14% (group I); 5%, 7%, and 7% (group II); and 2%, 5%, and 5% (group III) (I vs II,
P = not significant; I vs III,
P < .005; and II vs III,
P < .005). The 1-, 5-, and 10-year actuarial death rates from infection were 25%, 43%, and 50% (group I); 8%, 17%, and 29% (group II); and 6%, 11%, and 16% (group III) (I vs II,
P < .005; I vs III,
P < .005; and II vs III,
P < .05). The 1-, 5-, and 10-year actuarial death rates from graft coronary artery disease were 0%, 5%, and 13% (group I); 0%, 12%, and 19% (group II); and 1%, 6%, and 9% (group III) (I vs II,
P < .01; I vs III,
P < .005; and II vs III,
P = not significant). There have been 69 retransplants in 67 patients with 1-, 5-, and 10-year actuarial survivals of 49%, 27%, and 15%, respectively.
Conclusions: The evolution of 3 decades of experience with cardiac transplantation has resulted in improved overall survival. The incidence of rejection and of death from infection and graft coronary artery disease have decreased over time, primarily as a result of improvements in immunosuppression and in the prevention and treatment of infection. Continued advances in perioperative management and the development of more specific, less toxic immunosuppressive agents could further refine this initial experience and improve the survival and quality of life of patients after cardiac transplantation. (J Thorac Cardiovasc Surg 1999;117:939-51)
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