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Approximately 40 % of patients with bipolar disorder experience mixed episodes, defined as a manic state with depressive features, or manic symptoms in a patient with bipolar depression. Compared with bipolar patients without mixed features, patients with bipolar mixed states generally have more severe symptomatology, more lifetime episodes of illness, worse clinical outcomes and higher rates of comorbidities, and thus present a significant clinical challenge. Most clinical trials have investigated second-generation neuroleptic monotherapy, monotherapy with anticonvulsants or lithium, combination therapy, and electroconvulsive therapy (ECT). Neuroleptic drugs are often used alone or in combination with anticonvulsants or lithium for preventive treatment, and ECT is an effective treatment for mixed manic episodes in situations where medication fails or cannot be used. Common antidepressants have been shown to worsen mania symptoms during mixed episodes without necessarily improving depressive symptoms; thus, they are not recommended during mixed episodes. A greater understanding of pathophysiological processes in bipolar disorder is now required to provide a more accurate diagnosis and new personalised treatment approaches. Targeted, specific treatments developed through a greater understanding of bipolar disorder pathophysiology, capable of affecting the underlying disease processes, could well prove to be more effective, faster acting, and better tolerated than existing therapies, therefore providing better outcomes for individuals affected by bipolar disorder. Until such time as targeted agents are available, second-generation neuroleptics are emerging as the treatment of choice in the management of mixed states in bipolar disorder.

Intrinsic 40 K radioactive backgrounds from impurities of natural K in liquid scintillation cocktails have previously been demonstrated to limit their use in ultra-sensitive applications. This work explores two methodologies in parallel for the reduction of 40 K backgrounds in the cocktails, and lays the groundwork for use in ultra-sensitive applications. In one method, alternative low-K liquid scintillation matrix constituents were identified and in the other, a simple purification method for single components and finished cocktails was developed. Both methods were verified via ICP-MS analysis. Liquid scintillation counting of selected purified cocktails demonstrated background reduction, improved stability, and enhanced performance. The best performing purified cocktail was also counted on a custom-built ultra-low background liquid scintillation counter, with results below the detector background.

The performance of LSC cocktails in ultra-sensitive applications was evaluated. Backgrounds from radioactive contaminations in commercially available and in-house developed liquid scintillation cocktails were measured and compared to the predicted background levels of the ultra-low background liquid scintillation counter. Through the ICP-MS assay of the cocktails and their constituents, potassium impurities in the surfactant component were identified as a significant source of background, potentially limiting the use of LSC counting in ultra-sensitive applications. This work lays the groundwork for future research towards ultrapure LSC cocktails for ultrasensitive LSC counting.

ObjectivesBackgroundDigital mammography clearly distinguishes gland tissue density from the overlying nonglandular breast tissue coverage, which corresponds to the existing tissue between the skin and the superficial layer of the fascia superficialis surrounding the gland (i.e., dermis and subcutaneous fat). Preoperative digital imaging can determine the thickness of this breast tissue coverage, thus facilitating planning and reducing the rate of necrotic complications after direct to implant (DTI) reconstruction in nipple sparing mastectomy (NSM).MethodsThirty NSMs in 22 patients with type 3 tissue coverage (subcutaneous tissue thickness of 2 cm or more) were selected for DTI reconstruction after NSM to evaluate immediate skin flap/nipple areola complex ischemic complications and patient satisfaction.ResultsResults: We experienced no wound healing problems or ischemic complications immediately after surgery in our population. Only 1 seroma was observed as a shortterm complication. Quality of life and patients’ satisfaction level were optimal at 3 and 6 months follow-up, respectively. The aesthetic results have been evaluated as good/excellent in all cases.ConclusionsDTI immediate reconstruction with silicone implants following NSM appears to be a safe option in selected cases with enough tissue coverage, also providing a high level of patient satisfaction. The possibility of selecting cases for this procedure according to the preoperative digital mammogram showing more than 2 cm of superficial tissues thickness may help reducing the risk of immediate ischemic complications.

Precise measurement of neutrino oscillations, and hence the determination of their masses demands a quantitative understanding of neutrino-nucleus interactions. To this aim, two-body meson-exchange currents have to be accounted for along within realistic models of nuclear dynamics. We summarize our progresses towards the construction of a consistent framework, based on quantum Monte Carlo methods and on the spectral function approach, that can be exploited to accurately describe neutrino interactions with atomic nuclei over the broad kinematical region covered by neutrino experiments.

We carry out an ab initio calculation of the neutrino flux-folded inclusive cross sections, measured on ¹²C by the MiniBooNE and T2K collaborations in the charged-current quasielastic regime. The calculation is based on realistic two- and three-nucleon interactions, and on a realistic nuclear electroweak current with one-and two-nucleon terms that are constructed consistently with these interactions and reproduce low-energy electroweak transitions. Numerically exact quantum Monte Carlo methods are utilized to compute the nuclear weak response functions, by fully retaining many-body correlations in the initial and final states and interference effects between one- and two-body current contributions. We employ a nucleon axial form factor of the dipole form with Λ_(A) = 1.0 or 1.15 GeV, the latter more in line with a very recent lattice QCD determination. The calculated cross sections are found to be in good agreement with the neutrino data of MiniBooNE and T2K, and antineutrino MiniBooNE data, yielding a consistent picture of nuclei and their electroweak properties across a wide regime of energy and momenta.

The history of Central Eurasia and particularly pastoral-nomadic societies has long been defined by models of dependency. For millennia, nomadic societies have been thought to be dependent on sedentary societies for basic needs as well as cultural and political imports, representing “early-stage”, “less complex” societies. Scholars in recent decades across the humanities and social sciences have begun to supplant the older dependency theories with new ones that cast nomadic societies as more complex and capable of endogenous social evolution, historical agency, and broad cultural influence. However, change has been uneven between relevant disciplines. Historical narratives and archaeological records have been significantly reinterpreted to reflect social complexity, but nomadic societies are nearly completely ignored in cultural evolution and historical geography. Further, some ideas such as geographic determinism (“the empty steppe”) is still employed to explain nomadic migrations, invasions, and military conflicts in lieu of rich, native archives. This research begins by suggesting a novel assemblage of historical, social scientific, and complex systems theories in order to bring together many threads of knowledge about human societies into an interdisciplinary framework of modeling. This framework enables more coherent comparisons between verbal narratives and formal mathematical or computational models as assumption-laden vehicles of logic and communication. Using this framework, a conceptual agent-based model is suggested as a way to think about how wealth inequality might develop in a pastoral economy, how inequality leads to patron-client relationships, and how those socio-economic networks are maintained and strained under variable climatic conditions. Results of the modeling exercise indicate that notions of nomadic dependency are increasingly outdated and that high mobility, diffuse social and resource networks, climatic shocks, and common behaviors like social signaling are enough to produce complex internal social orders. Moreover, cross-cultural contact such as the trade in prestige goods or agricultural products can be more accurately understood as interdependency within a connected social world. Historical and anthropological evidence upending linear understandings of human societies continue to mount, closing the gap between how we think about our past and contemporary worlds. Nomadic societies of the past can be considered to have been “fully formed”, complex, and adaptive. Interdisciplinary frameworks, methods, and models continue to reveal the limits of disciplinary knowledge but also the possibilities of research that is greater than the sum of its parts.