Role of wnts in prostate cancer bone metastases

Prostate cancer (CaP) is unique among all cancers in that when it metastasizes to bone, it typically forms osteoblastic lesions (characterized by increased bone production). CaP cells produce many factors, including Wnts that are implicated in tumor-induced osteoblastic activity. In this prospectus, we describe our research on Wnt and the CaP bone phenotype. Wnts are cysteine-rich glycoproteins that mediate bone development in the embryo and promote bone production in the adult. Wnts have been shown to have autocrine tumor effects, such as enhancing proliferation and protecting against apoptosis. In addition, we have recently identified that CaP-produced Wnts act in a paracrine fashion to induce osteoblastic activity in CaP bone metastases. In addition to Wnts, CaP cells express the soluble Wnt inhibitor dickkopf-1 (DKK-1). It appears that DKK-1 production occurs early in the development of skeletal metastases, which results in masking of osteogenic Wnts, thus favoring osteolysis at the metastatic site. As metastases progress, DKK-1 expression decreases allowing for unmasking of Wnt's osteoblastic activity and ultimately resulting in osteosclerosis at the metastatic site. We believe that DKK-1 is one of the switches that transitions the CaP bone metastasis activity from osteolytic to osteoblastic. Wnt/DKK-1 activity fits a model of CaP-induced bone remodeling occurring in a continuum composed of an osteolytic phase, mediated by receptor activator of NFkB ligand (RANKL), parathyroid hormone-related protein (PTHRP) and DKK-1; a transitional phase, where environmental alterations promote expression of osteoblastic factors (Wnts) and decreases osteolytic factors (i.e., DKK-1); and an osteoblastic phase, in which tumor growth-associated hypoxia results in production of vascular endothelial growth factor and endothelin-1, which have osteoblastic activity. This model suggests that targeting both osteolytic activity and osteoblastic activity will provide efficacy for therapy of CaP bone metastases. J. Cell. Biochem. 97: 661–672, 2006. © 2005 Wiley-Liss, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/49527/1/20735_ftp.pd

Bosonic Qiskit

The practical benefits of hybrid quantum information processing hardware that contains continuous-variable objects (bosonic modes such as mechanical or electromagnetic oscillators) in addition to traditional (discrete-variable) qubits have recently been demonstrated by experiments with bosonic codes that reach the break-even point for quantum error correction and by efficient Gaussian boson sampling simulation of the Franck-Condon spectra of triatomic molecules that is well beyond the capabilities of current qubit-only hardware. The goal of this Co-design Center for Quantum Advantage (C2QA) project is to develop an instruction set architecture (ISA) for hybrid qubit/bosonic mode systems that contains an inventory of the fundamental operations and measurements that are possible in such hardware. The corresponding abstract machine model (AMM) would also contain a description of the appropriate error models associated with the gates, measurements and time evolution of the hardware. This information has been implemented as an extension of Qiskit. Qiskit is an opensource software development toolkit (SDK) for simulating the quantum state of a quantum circuit on a system with Python 3.7+ and for running the same circuits on prototype hardware within the IBM Quantum Lab. We introduce the Bosonic Qiskit software to enable the simulation of hybrid qubit/bosonic systems using the existing Qiskit software development kit. This implementation can be used for simulating new hybrid systems, verifying proposed physical systems, and modeling systems larger than can currently be constructed. We also cover tutorials and example use cases included within the software to study Jaynes- Cummings models, bosonic Hubbard models, plotting Wigner functions and animations, and calculating maximum likelihood estimations using Wigner functions

SnCQA: A hardware-efficient equivariant quantum convolutional circuit architecture

We propose SnCQA, a set of hardware-efficient variational circuits of equivariant quantum convolutional circuits respective to permutation symmetries and spatial lattice symmetries with the number of qubits $n$. By exploiting permutation symmetries of the system, such as lattice Hamiltonians common to many quantum many-body and quantum chemistry problems, Our quantum neural networks are suitable for solving machine learning problems where permutation symmetries are present, which could lead to significant savings of computational costs. Aside from its theoretical novelty, we find our simulations perform well in practical instances of learning ground states in quantum computational chemistry, where we could achieve comparable performances to traditional methods with few tens of parameters. Compared to other traditional variational quantum circuits, such as the pure hardware-efficient ansatz (pHEA), we show that SnCQA is more scalable, accurate, and noise resilient (with $20\times$ better performance on $3 \times 4$ square lattice and $200\% - 1000\%$ resource savings in various lattice sizes and key criterions such as the number of layers, parameters, and times to converge in our cases), suggesting a potentially favorable experiment on near-time quantum devices.Comment: 10 pages, many figures. IEEE QCE 2023, 1st best paper award in quantum algorithm

Supersymmetry in Slow Motion

We construct new theories of electroweak symmetry breaking that employ a combination of supersymmetry and discrete symmetries to stabilize the weak scale up to and beyond the energies probed by the LHC. These models exhibit conventional supersymmetric spectra but the fermion-sfermion-gaugino vertices are absent. This closes many conventional decay channels, thereby allowing several superpartners to be stable on collider time scales. This opens the door to the possibility of directly observing R-hadrons and three flavors of sleptons inside the LHC detectors.Comment: A reference added. The discussion on the Higgs sector expanded. The version accepted for publication in JHE

Individual cognitive stimulation therapy for dementia : a clinical effectiveness and cost-effectiveness pragmatic, multicentre, randomised controlled trial

Background Group cognitive stimulation therapy programmes can benefit cognition and quality of life for people with dementia. Evidence for home-based, carer-led cognitive stimulation interventions is limited. Objectives To evaluate the clinical effectiveness and cost-effectiveness of carer-delivered individual cognitive stimulation therapy (iCST) for people with dementia and their family carers, compared with treatment as usual (TAU). Design A multicentre, single-blind, randomised controlled trial assessing clinical effectiveness and cost-effectiveness. Assessments were at baseline, 13 weeks and 26 weeks (primary end point). Setting Participants were recruited through Memory Clinics and Community Mental Health Teams for older people. Participants A total of 356 caregiving dyads were recruited and 273 completed the trial. Intervention iCST consisted of structured cognitive stimulation sessions for people with dementia, completed up to three times weekly over 25 weeks. Family carers were supported to deliver the sessions at home. Main outcome measures Primary outcomes for the person with dementia were cognition and quality of life. Secondary outcomes included behavioural and psychological symptoms, activities of daily living, depressive symptoms and relationship quality. The primary outcome for the family carers was mental/physical health (Short Form questionnaire-12 items). Health-related quality of life (European Quality of Life-5 Dimensions), mood symptoms, resilience and relationship quality comprised the secondary outcomes. Costs were estimated from health and social care and societal perspectives. Results There were no differences in any of the primary outcomes for people with dementia between intervention and TAU [cognition: mean difference –0.55, 95% confidence interval (CI) –2.00 to 0.90; p-value = 0.45; self-reported quality of life: mean difference –0.02, 95% CI –1.22 to 0.82; p-value = 0.97 at the 6-month follow-up]. iCST did not improve mental/physical health for carers. People with dementia in the iCST group experienced better relationship quality with their carer, but there was no evidence that iCST improved their activities of daily living, depression or behavioural and psychological symptoms. iCST seemed to improve health-related quality of life for carers but did not benefit carers’ resilience or their relationship quality with their relative. Carers conducting more sessions had fewer depressive symptoms. Qualitative data suggested that people with dementia and their carers experienced better communication owing to iCST. Adjusted mean costs were not significantly different between the groups. From the societal perspective, both health gains and cost savings were observed. Conclusions iCST did not improve cognition or quality of life for people with dementia, or carers’ physical and mental health. Costs of the intervention were offset by some reductions in social care and other services. Although there was some evidence of improvement in terms of the caregiving relationship and carers’ health-related quality of life, iCST does not appear to deliver clinical benefits for cognition and quality of life for people with dementia. Most people received fewer than the recommended number of iCST sessions. Further research is needed to ascertain the clinical effectiveness of carer-led cognitive stimulation interventions for people with dementia

Functional Organization of a Neural Network for Aversive Olfactory Learning in Caenorhabditis elegans

Many animals use their olfactory systems to learn to avoid dangers, but how neural circuits encode naive and learned olfactory preferences, and switch between those preferences, is poorly understood. Here, we map an olfactory network, from sensory input to motor output, which regulates the learned olfactory aversion of Caenorhabditis elegans for the smell of pathogenic bacteria. Naive animals prefer smells of pathogens but animals trained with pathogens lose this attraction. We find that two different neural circuits subserve these preferences, with one required for the naive preference and the other specifically for the learned preference. Calcium imaging and behavioral analysis reveal that the naive preference reflects the direct transduction of the activity of olfactory sensory neurons into motor response, whereas the learned preference involves modulations to signal transduction to downstream neurons to alter motor response. Thus, two different neural circuits regulate a behavioral switch between naive and learned olfactory preferences.Organismic and Evolutionary BiologyPhysic

Space Mobile Network (SMN) User Demonstration Satellite (SUDS) for a Practical On-Orbit Demonstration of User Initiated Services (UIS)

This paper will discuss the various aspects of implementation of the Space Mobile Network (SMN) architecture framework within the context of operations of various nodes equipped with the User Initiated Services (UIS) protocol. These aspects include development of a Client-Server architecture in which space based Clients can create links with ground based Servers to negotiate passes with ground stations or contacts with the Tracking and Data Relay Satellite (TDRS) fleet. A key feature of this concept is that Users may require a mix of low data rate continuous contacts with one or more of the TDRS fleet and sporadic contacts with ground stations as passes become available. SUDS (SMN User Demonstration Satellite) will have the availability of TDRS contacts, the U.S. Naval Academy's ground station, NASA Near Earth Network ground sites and others. This mode of operations must be integrated within the traditional mode of scheduling contacts and passes. Thus, SUDS fits into a heterogeneous network operations concept of operations

Efficacy of miniaturized imacor trans-esophageal echocardiografm (TEE) prove in mechanical circulatory support.

Application of the miniaturized ImaCor Trans-Esophageal Echocardiogram (TEE) probe in Heart Transplant/Mechanical Cardiac Support Patients In the surgical cardiac care unit (SCCU), therapeutic interventions often need to be done at the bedside, necessitating the need for a rapidly employable diagnostic tool for the cardiac intensivist. We report the clinical utility of the miniature ImaCor TEE-probe in guiding management of post heart transplant (H-Txp) and mechanical cardiac support patients (MCS) and describe the economic benefit of such a device. This is an IRB approved retrospective review of MCS/H-Txp patients who had ImaCor TEE monitoring in the SCCU of our institution in 2011. The effect on management was stratified into 3 categories; Major (tamponade/device selection/RV failure), Moderate (weaning support device guidance/ inotrope management/fluid management/hemodynamic instability) and Minor (line placement/useful data). The ImaCor TEE-Probe was utilized in a total of 34 patients, of which 21 were either supported by MCS or were post H-Txp. Of these, 13 were on ECMO, 9 were post-VAD, 3 supported by the Impella device and 4 were post-H-Txp. 6 patients were placed on more than 1 method of MCS and 1 patient was supported by ECMO after a H-Txp. The device had a Major effect on management in 4 patients (19%), Moderate effect in 13 (62%) and a Minor effect in 4 (19%). The cost difference between this new device and the traditional TEE is also significant (900 USD vs 4000 USD). Our institution saved in excess of 150,000 USD with the use of this device instead of traditional TEE. This figure did not include the ability of this probe to be used repeatedly within a 72-hour time frame, and the potential cost of going to the operating theatre for further management. This device has proven to be an invaluable new adjunct in the SCCU by allowing previously unobtainable continuous real time monitoring of the MCS/H-Txp patient. Use of the ImaCor TEE-probe provides the cardiac intensivist with timely important clinical data that improves patient care and is economically advantageous

Long-term prognostic impact of cardiovascular comorbidities in patients with prostate cancer receiving androgen deprivation therapy: A population-based competing risk analysis.

Our study investigated how adverse cardiovascular outcomes are impacted by cardiovascular comorbidities in patients with prostate cancer treated by androgen deprivation therapy (ADT). Using prospective, population-based data, all Hong Kong patients with prostate cancer who received ADT during 1 January 1993 to 3 March 2021 were identified and followed up for the endpoint of cardiovascular hospitalization/mortality until 31 September 2021, whichever earlier. Multivariable competing risk regression was used to compare the endpoint's cumulative incidence between different combinations of major cardiovascular comorbidities (heart failure [HF], myocardial infarction [MI], stroke and/or arrhythmia), with noncardiovascular death as competing event. Altogether, 13 537 patients were included (median age 75.9 [interquartile range 70.0-81.5] years old; median follow-up 3.3 [1.5-6.7] years). Compared to those with none of prior HF/MI/stroke/arrhythmia, the incidence of the endpoint was not different in those with only stroke (subhazard ratio [SHR] 1.06 [95% confidence interval (CI): 0.92-1.23], P = .391), but was higher in those with only HF (SHR 1.67 [1.37-2.02], P < .001), arrhythmia (SHR 1.63 [1.35-1.98], P < .001) or MI (SHR 1.43 [1.14-1.79], P = .002). Those with ≥2 of HF/MI/stroke/arrhythmia had the highest incidence of the endpoint (SHR 1.94 [1.62-2.33], P < .001), among whom different major cardiovascular comorbidities had similar prognostic impacts, with the number of comorbidities present being significantly prognostic instead. In conclusion, in patients with prostate cancer receiving ADT, the sole presence of HF, MI or arrhythmia, but not stroke, may be associated with elevated cardiovascular risks. In those with ≥2 of HF/MI/stroke/arrhythmia, the number of major cardiovascular comorbidities may be prognostically more important than the type of comorbidities. [Abstract copyright: © 2023 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.