The relationships between depression and other outcomes of chronic illness caregiving

BACKGROUND: Many caregivers with chronically ill relatives suffer from depression. However, the relationship of depression to other outcomes of chronic caregiving remains unclear. This study tested a hypothesized model which proposed that hours of care, stressful life events, social support, age and gender would predict caregivers' outcomes through perceived caregiver stress. Depression was expected to mediate the relationship between perceived stress and outcomes of chronic caregiving (physical function, self-esteem, and marital satisfaction). METHODS: The sample for this secondary data analysis consisted of 236 and 271 subjects from the Americans' Changing Lives, Wave 1, 1986, and Wave 2, 1989, data sets. Measures were constructed from the original study. Structural equation modeling was used to test the hypothesized model, and an exploratory structural modeling method, specification search, was used to develop a data-derived model. Cross-validation was used to verify the paths among variables. RESULTS: Hours of care, age, and gender predicted caregivers' outcomes directly or through perceived caregiver stress (p < .01). Depression mediated the relationship between perceived stress and psychological outcomes and explained 40% and 11% of the variance in self-esteem and marital satisfaction, respectively. CONCLUSION: Depression predicted psychological outcomes. Whether depression predicts physical health outcomes needs to be further explored

Safety of intravenous ferric carboxymaltose versus oral iron in patients with nondialysis-dependent CKD: an analysis of the 1-year FIND-CKD trial.

Background: The evidence base regarding the safety of intravenous (IV) iron therapy in patients with chronic kidney disease (CKD) is incomplete and largely based on small studies of relatively short duration. Methods: FIND-CKD (ClinicalTrials.gov number NCT00994318) was a 1-year, open-label, multicenter, prospective study of patients with nondialysis-dependent CKD, anemia and iron deficiency randomized (1:1:2) to IV ferric carboxymaltose (FCM), targeting higher (400-600 µg/L) or lower (100-200 µg/L) ferritin, or oral iron. A post hoc analysis of adverse event rates per 100 patient-years was performed to assess the safety of FCM versus oral iron over an extended period. Results: The safety population included 616 patients. The incidence of one or more adverse events was 91.0, 100.0 and 105.0 per 100 patient-years in the high ferritin FCM, low ferritin FCM and oral iron groups, respectively. The incidence of adverse events with a suspected relation to study drug was 15.9, 17.8 and 36.7 per 100 patient-years in the three groups; for serious adverse events, the incidence was 28.2, 27.9 and 24.3 per 100 patient-years. The incidence of cardiac disorders and infections was similar between groups. At least one ferritin level ≥800 µg/L occurred in 26.6% of high ferritin FCM patients, with no associated increase in adverse events. No patient with ferritin ≥800 µg/L discontinued the study drug due to adverse events. Estimated glomerular filtration rate remained the stable in all groups. Conclusions: These results further support the conclusion that correction of iron deficiency anemia with IV FCM is safe in patients with nondialysis-dependent CKD

Dynamics of hole singlet-triplet qubits with large g-factor differences

The spin-orbit interaction permits to control the state of a spin qubit via electric fields. For holes it is particularly strong, allowing for fast all electrical qubit manipulation, and yet an in-depth understanding of this interaction in hole systems is missing. Here we investigate, experimentally and theoretically, the effect of the cubic Rashba spin-orbit interaction on the mixing of the spin states by studying singlet-triplet oscillations in a planar Ge hole double quantum dot. Landau-Zener sweeps at different magnetic field directions allow us to disentangle the effects of the spin-orbit induced spin-flip term from those caused by strongly site-dependent and anisotropic quantum dot g tensors. Our work, therefore, provides new insights into the hole spin-orbit interaction, necessary for optimizing future qubit experiments

A singlet triplet hole spin qubit in planar Ge

Spin qubits are considered to be among the most promising candidates for building a quantum processor. GroupIV hole spin qubits have moved into the focus of interest due to the ease of operation and compatibility with Si technology. In addition, Ge offers the option for monolithic superconductor-semiconductor integration. Here we demonstrate a hole spin qubit operating at fields below 10 mT, the critical field of Al, by exploiting the large out-of-plane hole g-factors in planar Ge and by encoding the qubit into the singlet-triplet states of a double quantum dot. We observe electrically controlled g-factor-difference-driven and exchange-driven rotations with tunable frequencies exceeding 100 MHz and dephasing times of 1 $\mu$s which we extend beyond 150 $\mu$s with echo techniques. These results demonstrate that Ge hole singlet-triplet qubits are competing with state-of-the art GaAs and Si singlet-triplet qubits. In addition, their rotation frequencies and coherence are on par with Ge single spin qubits, but they can be operated at much lower fields underlining their potential for on chip integration with superconducting technologies

Cross-architecture tuning of silicon and SiGe-based quantum devices using machine learning

The potential of Si and SiGe-based devices for the scaling of quantum circuits is tainted by device variability. Each device needs to be tuned to operation conditions and each device realisation requires a different tuning protocol. We demonstrate that it is possible to automate the tuning of a 4-gate Si FinFET, a 5-gate GeSi nanowire and a 7-gate Ge/SiGe heterostructure double quantum dot device from scratch with the same algorithm. We achieve tuning times of 30, 10, and 92 min, respectively. The algorithm also provides insight into the parameter space landscape for each of these devices, allowing for the characterization of the regions where double quantum dot regimes are found. These results show that overarching solutions for the tuning of quantum devices are enabled by machine learning

An oncolytic adenovirus coding for a variant interleukin 2 cytokine improves response to chemotherapy through enhancement of effector lymphocyte cytotoxicity, fibroblast compartment modulation and mitotic slippage

Pancreatic ductal adenocarcinoma (PDAC) is a highly treatment-resistant cancer. Currently, the only curative treatment for PDAC is surgery, but most patients are diagnosed with metastatic disease and thus outside the scope of surgery. The majority of metastatic patients receive chemotherapy, but responses are limited. New therapeutics are thus urgently needed for PDAC. One major limitation in treating PDAC has been the highly immunosuppressive tumor microenvironment (TME) which inhibits anti-cancer immune responses. We have constructed an oncolytic adenovirus coding for a variant the interleukin 2 molecule, Ad5/3-E2F-d24-vIL2 (also known as TILT-452, and “vIL-2 virus”), with preferential binding to IL-2 receptors on the surface of effector lymphocytes over T regulatory cells (T regs). In the present study this virus was evaluated in combination with nab-paclitaxel and gemcitabine chemotherapy in Panc02 mouse model. Ad5/3-E2F-d24-vIL2 showed marked PDAC cell killing in vitro, alongside induction of mitotic slippage and immunogenic cell death in PDAC cell lines, when combined with chemotherapy. Increased survival was seen in vivo with 80% of animals surviving long term, when compared to chemotherapy alone. Moreover, combination therapy mediated enhanced tumor growth control, without observable toxicities in internal organs or external features. Survival and tumor control benefits were associated with activation of tumor infiltrating immune cells, downregulation of inhibitory signals, change in fibroblast populations in the tumors and changes in intratumoral cytokines, with increased chemokine amounts (CCL2, CCL3, CCL4) and anti-tumor cytokines (IFN-γ and TNFα). Furthermore, vIL-2 virus in combination with chemotherapy efficiently induced tumor protection upon rechallenge, that was extended to a previously non-encountered cancer cell line. In conclusion, Ad5/3-E2F-d24-vIL2 is a promising immunotherapy candidate when combined with nab-paclitaxel and gemcitabine

Universal control of four singlet-triplet qubits

The coherent control of interacting spins in semiconductor quantum dots is of strong interest for quantum information processing as well as for studying quantum magnetism from the bottom up. Here, we present a $2\times4$ germanium quantum dot array with full and controllable interactions between nearest-neighbor spins. As a demonstration of the level of control, we define four singlet-triplet qubits in this system and show two-axis single-qubit control of each qubit and SWAP-style two-qubit gates between all neighbouring qubit pairs, yielding average single-qubit gate fidelities of 99.49(8)-99.84(1)% and Bell state fidelities of 73(1)-90(1)%. Combining these operations, we experimentally implement a circuit designed to generate and distribute entanglement across the array. A remote Bell state with a fidelity of 75(2)% and concurrence of 22(4)% is achieved. These results highlight the potential of singlet-triplet qubits as a competing platform for quantum computing and indicate that scaling up the control of quantum dot spins in extended bilinear arrays can be feasible.In the updated version, data on single- and two-qubit gate fidelities, as well as two-qubit Bell state fidelities, have been adde

Evaluation of exercise on individuals with dementia and their carers: a randomised controlled trial

Background Almost all of the 820,000 people in the UK with dementia will experience Behavioural and Psychological Symptoms of Dementia (BPSD). However, research has traditionally focused on treating cognitive symptoms, thus neglecting core clinical symptoms that often have a more profound impact on living with dementia. Recent evidence (Kales et al, 2007; Ballard et al, 2009) indicates that the popular approach to managing BPSD - prescription of anti-psychotic medication - can increase mortality and the risk of stroke in people with dementia as well as impair quality of life and accelerate cognitive decline. Consequently, there is a need to evaluate the impact that non-pharmacological interventions have on BPSD; we believe physical exercise is a particularly promising approach. Methods/Design We will carry out a pragmatic, randomised, single-blind controlled trial to evaluate the effectiveness of exercise (planned walking) on the behavioural and psychological symptoms of individuals with dementia. We aim to recruit 146 people with dementia and their carers to be randomized into two groups; one will be trained in a structured, tailored walking programme, while the other will continue with treatment as usual. The primary outcome (BPSD) will be assessed with the Neuropsychiatric Inventory (NPI) along with relevant secondary outcomes at baseline, 6 and 12 weeks. Discussion Designing this study has been challenging both ethically and methodologically. In particular to design an intervention that is simple, measurable, safe, non-invasive and enjoyable has been testing and has required a lot of thought. Throughout the design, we have attempted to balance methodological rigour with study feasibility. We will discuss the challenges that were faced and overcome in this paper

Need-driven dementia-compromised behavior: An alternative view of disruptive behavior

The disruptive behavior of persons with dementia is a problem of considerable clinical interest and growing scientific concern. This paper offers a view of these behaviors as expressions of unmet needs or goals and provides a comprehensive conceptual framework to guide further research and clinical practice. Empiricalfindings and clinical impressions related to wandering, vocalizations and aggression to support and illustrate the framework are presentedPeer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66887/2/10.1177_153331759601100603.pd