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While the field of MIMO transmission has been explored over the past decade mainly theoretically, relatively few results exist on how these transmissions perform over realistic, imperfect channels. The reason for this is that measurement equipment is expensive, difficult to obtain, and often inflexible when a multitude of transmission parameters are of interest. This paper presents a flexible testbed developed to examine MIMO algorithms and channel models described in literature by transmitting data at through real, physical channels, supporting simultaneously four transmit and four receive antennas. Operation is performed directly from Matlab allowing for a cornucopia of real-world experiments with minimum effort. Examples measuring bit error rates on space-time block codes are provided in the paper.

Background: The National Cancer Institute Cancer Screening Research Network is launching a pilot study (Vanguard) to determine feasibility of successful completion of a clinical trial of multicancer detection tests. This focus group study reports perceptions of primary care physicians and laypersons of different clinical trial designs and willingness to participate in a multicancer detection clinical trial., Methods: We undertook 14 focus groups with 88 laypersons and 6 focus groups with 45 primary care physicians. Participants were shown graphics of clinical trial designs and asked for their reactions. Focus group recordings were transcribed verbatim, and thematic analysis of the transcripts were conducted to identify emergent themes., Results: Primary care physician and layperson participants recognized the importance of conducting clinical trials to determine the clinical utility of multicancer detection tests. Primary care physicians expressed reluctance to participate in trials because of workload burden, and laypersons expressed hesitancy about enrolling in the control group. Primary care physicians and laypersons expressed concern about a study design in which multicancer detection test results would not be returned to the control group (intended effect), but they respectively indicated a willingness to refer patients to, or participate in, a multicancer detection test clinical trial given transparent and clear communication on collection and use of biospecimens and data, particularly if a multicancer detection test would eventually be run and results eventually returned., Conclusion: This study yielded important insights to guide trial design in planning prospective evaluation of multicancer detection testing. Maintaining transparency and trust while possibly withholding multicancer detection test results to maximize trial feasibility and efficiency is of particular concern., (Published by Oxford University Press 2024.)

School-based mental health literacy (MHL) programs can increase knowledge, reduce stigma, and encourage help-seeking behaviors in school-aged children. Yet, MHL intervention effects are inconsistent and unsustainable over time, and scholars have called for more theoretical work to address these limitations. The purpose of this theoretical review is to investigate how theory is utilized in MHL interventions, explore the interpersonal communication processes integrated in MHL interventions, and uncover the theoretical assumptions made in MHL interventions about interpersonal communication. We identified 27 articles for inclusion and utilized both content and interpretive analyses. Findings suggest that very few MHL interventions are based in theory; interpersonal communication is a central component within MHL programming; and numerous assumptions are made about interpersonal communication within MHL interventions that need to be addressed theoretically and empirically. Accordingly, we recommend that MHL intervention content and delivery practices are grounded in interpersonal communication theory related to disclosure and social support (seeking and provision). Additionally, teaching disclosure and social support skills may be a productive way for MHL interventions to help students build self-efficacy in communication about mental health for themselves and others.

For people living with mental illness, support from social network members, including family, romantic partners, and friends, is critical but often inadequate. However, robust theoretical explanations for why it might it be difficult to support people living with mental illness are lacking. We assessed an appraisal-based model of uncertainty, hypothesizing that fear and anxiety and supportive communication efficacy mediate the association between mental illness uncertainty and support provision (i.e., quantity and quality). We also predicted that perceptions of others' communication about their mental illness (i.e., ambiguity and volume) would exacerbate feelings of fear and anxiety in relation to uncertainty. Analyses of data gathered from 300 individuals across the United States ( M age = 34.07, SD  = 9.49; 50% female) supported our central prediction; uncertainty had a negative direct or indirect effect on all support types and overall support quality, partly through decreases in supportive communication efficacy. Counter to predictions, fear and anxiety positively predicted support quantity for all types. Findings of this study point to a difficult situation for social network members: although uncertainty seems to motivate support provision by activating fear and anxiety, this effect could be undermined for forms of support that require complex communication skills (e.g., emotional, esteem, overall quality) through corresponding decreases in supportive communication efficacy. We discuss the theoretical and practical implications of this research for social support and relationships within the context of mental illness.

Here, we describe a nanocarrier system that can transfer chitosan nanoparticles loaded with either small peptides such as the caspase inhibitor Z-DEVD-FMK or a large peptide like basic fibroblast growth factor across the blood-brain barrier. The nanoparticles are selectively directed to the brain and are not measurably taken up by the liver and spleen. Intravital fluorescent microscopy provides an opportunity to study the penetration kinetics of nanoparticles loaded with fluorescent agents such as Nile red. Nanoparticles functionalized with anti-transferrin antibody and loaded with peptides efficiently provided neuroprotection when systemically administered either as a formulation bearing a single peptide or a mixture of them. Failure of brain permeation of the nanoparticles after inhibition of vesicular transcytosis by imatinib as well as when nanoparticles were not functionalized with anti-transferrin antibody indicates that this nanomedicine formulation is rapidly transported across the blood-brain barrier by receptor-mediated transcytosis.

Although growth factors and anti-apoptotic peptides have been shown to be neuroprotective in stroke models, translation of these experimental findings to clinic is hampered by limited penetration of peptides to the brain. Here, we show that a large peptide like the basic fibroblast growth factor (bFGF) and a small peptide inhibitor of caspase-3 (z-DEVD-FMK) can effectively be transported to the brain after systemic administration by incorporating these peptides to brain-targeted nanoparticles (NPs). Chitosan NPs were loaded with peptides and then functionalized by conjugating with antibodies directed against the transferrin receptor-1 on brain endothelia to induce receptor-mediated transcytosis across the blood-brain barrier (BBB). Pre-ischemic systemic administration of bFGF- or z-DEVD-FMK-loaded NPs significantly decreased the infarct volume after 2-hour middle cerebral artery occlusion and 22-hour reperfusion in mice. Co-administration of bFGF- or z-DEVD-FMK-loaded NPs reduced the infarct volume further and provided a 3-hour therapeutic window. bFGF-loaded NPs were histologically detected in the brain parenchyma and also restored ischemia-induced Akt dephosphorylation. The neuroprotection was not observed when receptor-mediated transcytosis was inhibited with imatinib or when bFGF-loaded NPs were not conjugated with the targeting antibody, which enables them to cross the BBB. Nanoparticles targeted to brain are promising drug carriers to transport large as well as small BBB-impermeable therapeutics for neuroprotection against stroke.

There is an urgent need to develop new therapeutic approaches for the treatment of severe neurological trauma, such as stroke and spinal cord injuries. However, many drugs with potential neuropharmacological activity, such as adenosine, are inefficient upon systemic administration because of their fast metabolization and rapid clearance from the bloodstream. Here, we show that conjugation of adenosine to the lipid squalene and the subsequent formation of nanoassemblies allows prolonged circulation of this nucleoside, providing neuroprotection in mouse stroke and rat spinal cord injury models. The animals receiving systemic administration of squalenoyl adenosine nanoassemblies showed a significant improvement of their neurologic deficit score in the case of cerebral ischaemia, and an early motor recovery of the hindlimbs in the case of spinal cord injury. Moreover, in vitro and in vivo studies demonstrated that the nanoassemblies were able to extend adenosine circulation and its interaction with the neurovascular unit. This Article shows, for the first time, that a hydrophilic and rapidly metabolized molecule such as adenosine may become pharmacologically efficient owing to a single conjugation with the lipid squalene.

The current treatment of neurological and psychiatric diseases is far beyond being satisfactory. In addition to highly complex disease mechanisms, the blood-brain barrier (BBB) also remains as a challenge by limiting the delivery of the majority of currently available therapeutics to the central nervous system. Several approaches taking advantage of molecular and physicochemical characteristics of the BBB have been developed recently to improve drug delivery to the brain. Here, we introduce a nanomedicine that can efficiently transport BBB-impermeable peptides to the brain. This nanomedicine is made of chitosan nanoparticles into which considerable amounts of a peptide can be incorporated. The nanoparticle surface is modified with polyethylene glycol to enhance the plasma residence time by preventing their capture by the reticuloendothelial system. Monoclonal antibodies against the transferrin receptor (TfR), which is highly expressed on the brain capillary endothelium, are conjugated to nanoparticles via biotin-streptavidin bonds. The activation of TfR by the nanoparticle-antibody complex induces transcytosis and thus delivers the loaded drug to the brain. Penetration of nanoparticles to the brain can be illustrated in vivo by intravital microscopy as well as ex vivo by fluorescence or electron microscopy. N-Benzyloxycarbonyl-Asp(OMe)-Glu(OMe)-Val-Asp(OMe)-fluoromethyl ketone (Z-DEVD-FMK)-loaded nanoparticles rapidly release their contents within brain parenchyma, inhibit ischemia-induced caspase-3 activity, and thereby provide neuroprotection., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Here, we describe a nanocarrier system that can transfer chitosan nanoparticles loaded with either small peptides such as the caspase inhibitor Z-DEVD-FMK or a large peptide like basic fibroblast growth factor across the blood-brain barrier. The nanoparticles are selectively directed to the brain and are not measurably taken up by liver and spleen. Intravital fluorescent microscopy provides an opportunity to study the penetration kinetics of nanoparticles loaded with fluorescent agents such as Nile red, and has demonstrated that this nanomedicine formulation is rapidly transported across the blood-brain barrier.

Caspases play an important role as mediators of cell death in acute and chronic neurological disorders. Although peptide inhibitors of caspases provide neuroprotection, they have to be administered intracerebroventricularly because they cannot cross the blood-brain barrier (BBB). Herein, we present a nanocarrier system that can transfer chitosan nanospheres loaded with N-benzyloxycarbonyl-Asp(OMe)-Glu(OMe)-Val-Asp(OMe)-fluoromethyl ketone (Z-DEVD-FMK), a relatively specific caspase-3 inhibitor, across BBB. Caspase-3 was chosen as a pharmacological target because of its central role in cell death. Polyethylene glycol-coated nanospheres were conjugated to an anti-mouse transferrin receptor monoclonal antibody (TfRMAb) that selectively recognizes the TfR type 1 on the cerebral vasculature. We demonstrate with intravital microscopy that this nanomedicine is rapidly transported across the BBB without being measurably taken up by liver and spleen. Pre- or post-treatment (2 h) with intravenously injected Z-DEVD-FMK-loaded nanospheres dose dependently decreased the infarct volume, neurological deficit, and ischemia-induced caspase-3 activity in mice subjected to 2 h of MCA occlusion and 24 h of reperfusion, suggesting that they released an amount of peptide sufficient to inhibit caspase activity. Similarly, nanospheres inhibited physiological caspase-3 activity during development in the neonatal mouse cerebellum on postnatal day 17 after closure of the BBB. Neither nanospheres functionalized with TfRMAb but not loaded with Z-DEVD-FMK nor nanospheres lacking TfRMAb but loaded with Z-DEVD-FMK had any effect on either paradigm, suggesting that inhibition of caspase activity and subsequent neuroprotection were due to efficient penetration of the peptide into brain. Thus, chitosan nanospheres open new and exciting opportunities for brain delivery of biologically active peptides that are useful for the treatment of CNS disorders.

Rapid cycling is a pattern of presentation of bipolar disorder that specifies the course of the illness and is associated with a greater morbidity. The validity of rapid cycling as a distinct course modifier for bipolar disorder has been demonstrated and the term has been incorporated into the DSM-IV. The phenomenon of rapid cycling tends to appear late in the course of the disorder, occurs more frequently among females, and is more frequently seen in patients with bipolar type II disorder. Stimulants such as cocaine may also play some role in rapid-cycling. It is generally accepted that a recent history of rapid cycling predicts non-response to monotherapy with lithium and probably carbamazepine as well; however it is also possible that concurrent use of antidepressants may play a role in destabilizing the illness course under these agents. Thus, clinical considerations suggest that discontinuing antidepressants may facilitate the recovery process. Among clinically available monotherapies, valproate and lamotrigine appear to be the most useful clinically. However, other treatments such as lithium, carbamazepine, the atypical antipsychotic agents, thyroid hormone, and bupropion are frequently needed augmentation strategies. Electroconvulsive therapy may also prove efficacious in selected cases. The present paper provides a critical review of the evidence for the foregoing clinical issues in rapid cycling.

The phenomenon of frequent cycling in bipolar disorder was first recognized by Emil Kraepelin in 1913. More recently, rapid cycling has been reported to be a predictor of nonresponse to treatment. At the time of presentation, most patients with DSM-IV-defined rapid cycling appear to be in the depressed phase of their illness. Frequent and more severe episodes of depression appear to be the hallmark of rapid cycling. Reported in this article are recent preliminary data suggesting that the combination of lithium and divalproex sodium administered continuously over 6 months appears to result in marked acute and continuation antimanic efficacy in 85% of patients and marked antidepressant efficacy in 60%. However, only one half of patients experienced bimodal stabilization. Comorbid alcohol, cannabis, and/or cocaine abuse and/or dependence did not appear to directly affect the spectrum of efficacy of lithium and divalproex or response rates in compliant patients. Comorbidity appeared to alter prognosis by increasing the prevalence of poor compliance. The majority of patients receiving lithium and divalproex who required additional treatment were depressed, suggesting that the frequent recurrence of depression is the primary unmet need in patients with rapid cycling. The use of antidepressants in this population has been discouraged because of concerns about the possibility of cycle acceleration. There exists a need for a pharmacotherapy that not only possesses marked acute antidepressant properties, but that does so without inducing switching or cycle acceleration. A double-blind, placebo-controlled trial of lamotrigine monotherapy in bipolar I depression has demonstrated efficacy without causing switching at a rate exceeding placebo; however, this initial study excluded patients with rapid cycling. To explore the efficacy of lamotrigine in rapid cycling, a recent multicenter study has examined lamotrigine as a maintenance therapy for this population. The results indicate that lamotrigine may be a useful treatment for patients with rapid-cycling bipolar II disorder and that this drug has begun to address this unmet need.