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Exercise facilitates hippocampal neurogenesis and neuroplasticity that in turn, promotes cognitive function. Our previous studies have demonstrated that in male mice, voluntary exercise enables hippocampus-dependent learning in conditions that are normally subthreshold for long-term memory formation in sedentary animals. Such cognitive enhancement can be maintained long after exercise has ceased and can be re-engaged by a subsequent subthreshold exercise session, suggesting exercise-induced benefits are temporally dynamic. In females, the extent to which the benefits of exercise can be maintained and the mechanisms underlying this maintenance have yet to be defined. Here, we examined the exercise parameters required to initiate and maintain the benefits of exercise in female C57BL/6J mice. Using a subthreshold version of the hippocampus-dependent task called object-location memory (OLM) task, we show that 14d of voluntary exercise enables learning under subthreshold acquisition conditions in female mice. Following the initial exercise, a 7d sedentary delay results in diminished performance, which can be re-facilitated when animals receive 2d of reactivating exercise following the sedentary delay. Assessment of estrous cycle reveals enhanced wheel running activity during the estrus phase relative to the diestrus phase, whereas estrous phase on training or test had no effect on OLM performance. Utilizing the same exercise parameters, we demonstrate that 14d of exercise enhances long-term potentiation (LTP) in the CA1 region of the hippocampus, an effect that persists throughout the sedentary delay and following the reactivating exercise session. Previous studies have proposed exercise-induced BDNF upregulation as the mechanism underlying exercise-mediated benefits on synaptic plasticity and cognition. However, our assessment of hippocampal Bdnf mRNA expression following memory retrieval reveals no difference between exercise conditions and control, suggesting that persistent Bdnf upregulation may not be required for maintenance of exercise-induced benefits. Together, our data indicate that 14d of voluntary exercise can initiate long-lasting benefits on neuroplasticity and cognitive function in female mice, establishing the first evidence on the temporal endurance of exercise-induced benefits in females.

Since the publication of this work, M. Gad has changed their name from M.G. Elabd. This has now been amended in the HTML and PDF versions of the article.

Epigenetic mechanisms regulate processes of neuroplasticity critical to cocaine-induced behaviors. This includes the Class I histone deacetylase (HDAC) HDAC3, known to act as a negative regulator of cocaine-associated memory formation within the nucleus accumbens (NAc). Despite this, it remains unknown how cocaine alters HDAC3-dependent mechanisms. Here, we profiled HDAC3 expression and activity in total NAc mouse tissue following cocaine exposure. Although chronic cocaine did not affect expression of Hdac3 within the NAc, chronic cocaine did affect promoter-specific changes in HDAC3 and H4K8Ac occupancy. These changes in promoter occupancy correlated with cocaine-induced changes in expression of plasticity-related genes. To causally determine whether cocaine-induced plasticity is mediated by HDAC3's deacetylase activity, we overexpressed a deacetylase-dead HDAC3 point mutant (HDAC3-Y298H-v5) within the NAc of adult male mice. We found that disrupting HDAC3's enzymatic activity altered selective changes in gene expression and synaptic plasticity following cocaine exposure, despite having no effects on cocaine-induced behaviors. In further assessing HDAC3's role within the NAc, we observed that chronic cocaine increases Hdac3 expression in Drd1 but not Drd2-cells of the NAc. Moreover, we discovered that HDAC3 acts selectively within D1R cell-types to regulate cocaine-associated memory formation and cocaine-seeking. Overall, these results suggest that cocaine induces cell-type-specific changes in epigenetic mechanisms to promote plasticity important for driving cocaine-related behaviors.SIGNIFICANCE STATEMENT Drugs of abuse alter molecular mechanisms throughout the reward circuitry that can lead to persistent drug-associated behaviors. Epigenetic regulators are critical drivers of drug-induced changes in gene expression. Here, we demonstrate that the activity of an epigenetic enzyme promotes neuroplasticity within the nucleus accumbens (NAc) critical to cocaine action. In addition, we demonstrate that these changes in epigenetic activity drive cocaine-seeking behaviors in a cell-type-specific manner. These findings are key in understanding and targeting cocaine's impact of neural circuitry and behavior.

Deep space travel presents a number of measurable risks including exposure to a spectrum of radiations of varying qualities, termed galactic cosmic radiation (GCR) that are capable of penetrating the spacecraft, traversing through the body and impacting brain function. Using rodents, studies have reported that exposure to simulated GCR leads to cognitive impairments associated with changes in hippocampus function that can persist as long as one-year post exposure with no sign of recovery. Whether memory can be updated to incorporate new information in mice exposed to GCR is unknown. Further, mechanisms underlying long lasting impairments in cognitive function as a result of GCR exposure have yet to be defined. Here, we examined whether whole body exposure to simulated GCR using 6 ions and doses of 5 or 30 cGy interfered with the ability to update an existing memory or impact hippocampal synaptic plasticity, a cellular mechanism believed to underlie memory processes, by examining long term potentiation (LTP) in acute hippocampal slices from middle aged male mice 3.5-5 months after radiation exposure. Using a modified version of the hippocampus-dependent object location memory task developed by our lab termed "Objects in Updated Locations" (OUL) task we find that GCR exposure impaired hippocampus-dependent memory updating and hippocampal LTP 3.5-5 months after exposure. Further, we find that impairments in LTP are reversed through one-time systemic subcutaneous injection of the histone deacetylase 3 inhibitor RGFP 966 (10 mg/kg), suggesting that long lasting impairments in cognitive function may be mediated at least in part, through epigenetic mechanisms.

Background: Premature ventricular contractions (PVCs) commonly coexist with cardiomyopathy. Recently, PVCs have been identified as a possible cause of cardiomyopathy. We developed a PVC-induced cardiomyopathy animal model using a novel premature pacing algorithm to assess timeframe and reversibility of this cardiomyopathy and examine the associated histopathologic abnormalities.Methods and Results: Thirteen mongrel dogs were implanted with a specially programmed pacemaker capable of simulating ventricular extrasystoles. Animals were randomly assigned to either 12 weeks of bigeminal PVCs (n = 7) or no PVCs (control, n = 6). Continuous 24-hour Holter monitoring corroborated ventricular bigeminy in the PVC group (PVC, 49.8% versus control, < 0.01%; P<0.0001). After 12 weeks, only the PVC group had cardiomyopathy, with a significant reduction in left ventricular ejection fraction (PVC, 39.7 ± 5.4% versus control, 60.7 ± 3.8%; P < 0.0001) and an increase in left ventricular end-systolic dimension (PVC, 33.3 ± 3.5 mm versus control, 23.7 ± 3.6 mm; P < 0.001). Ventricular effective refractory period showed a trend to prolong in the PVC group. PVC-induced cardiomyopathy was resolved within 2 to 4 weeks after discontinuation of PVCs. No inflammation, fibrosis, or changes in apoptosis and mitochondrial oxidative phosphorylation were observed with PVC-induced cardiomyopathy.Conclusions: This novel PVC animal model demonstrates that frequent PVCs alone can induce a reversible form of cardiomyopathy in otherwise structurally normal hearts. PVC-induced cardiomyopathy lacks gross histopathologic and mitochondrial abnormalities seen in other canine models of cardiomyopathy. [ABSTRACT FROM AUTHOR]

Introduction: Implantable cardioverter-defibrillators (ICDs) are susceptible to oversensing of extracardiac signals, also known as electromagnetic interference (EMI). We report a case of an unusual source of electrical interference of only the high voltage (HV) impedance measurement in the Teligen™ ICD (Boston Scientific, St. Paul, MN, USA) caused by electrical interference from an electrosurgical generator with an electrocautery patch located in close proximity to the ICD pulse generator. Method and Results: A patient underwent an uneventful implant of a Boston Scientific Teligen™ 100 ICD. Once the device was inserted in a pocket, interrogation of the device repeatedly demonstrated HV electrode impedance measurements between <20 and 40Ω and noise only on the HV electrode. A new lead and generator were implanted without a change in the interrogation results. The erroneous measurements of HV impedance were caused by a combination of the close proximity of the electrocautery patch to the ICD generator. The continuous low-amplitude current emitted by the contact quality monitoring system of the electrosurgical cautery generator interfered with an equally weak current delivered through the lead by the device to measurement HV impedance. The Medtronic Virtuoso™ (Medtronic Inc., Minneapolis, MN, USA) ICD and the St. Jude Medical Current™ DR (St. Jude Medical, St. Paul, MN, USA) ICD were not affected by the patch due to greater magnitude of current delivered by the device to measure HV electrode impedance. Conclusion: It is important that the operator must be aware of any potential source of EMI, as it may affect the device and require immediate troubleshooting. Failure to recognize this interaction may result in inappropriate and unnecessary pulse generator replacement. (PACE 2010; 994–998) [ABSTRACT FROM AUTHOR]

The quinidine-like effects of some antidepressant drugs (particularly tricyclic antidepressants) and many antipsychotic drugs (particularly the phenothiazines) confound treatment of psychosis and depression in patients with major mental illness. This is especially true among elderly patients with existing risk factors for corrected QT (QTc) interval prolongation. We used PubMed, previously reported review articles and the extensive personal files of the authors to identify cases of subjects aged>or=60 years who developed QTc interval prolongation, polymorphic ventricular tachycardia (PVT)/torsade de pointes (TdP) and/or sudden cardiac death while taking antipsychotic or antidepressant drugs or a combination of these medications. We identified 37 patients who had taken, in total, 46 antipsychotic or antidepressant drugs. Our most striking finding was that almost four-fifths of our cases involved women. When the 14 critically ill subjects receiving haloperidol intravenously were excluded, 91.3% of our subjects were women. Almost three-quarters of our study subjects had cardiovascular disease. Intravenous administration of haloperidol in the critically ill and profoundly agitated elderly warrants particular comment. Of the 14 subjects in this category identified, six were men and eight were women. In 13 cases, the drug dose far exceeded the 2 mg necessary to produce an antipsychotic effect. These clinicians were using an agent to achieve sedation that usually requires very high doses in the critically ill and profoundly agitated elderly to achieve this effect. Inclusion criteria for our literature review required antipsychotic and/or antidepressant drug-induced QTc interval prolongation. Even so, our finding that 31 of our 37 subjects developed PVT is sobering. However, the reader should not conclude that drug-induced QTc interval prolongation is highly predictive of PVT or its TdP subtype. All of our study subjects had at least two risk factors for TdP, with age and sex being the most common. We included the rare case of a patient with congenital long QT syndrome who developed further lengthening of the QTc interval and TdP when prescribed an antidepressant drug well known to produce QTc interval prolongation. We conclude with recommendations for clinicians not expert in the specialty of cardiology to deal with the many questions raised in this review. Specifically, such clinicians treating elderly patients with antipsychotic and antidepressant drugs that may prolong the QTc interval should aggressively obtain a baseline ECG for elderly female patients with additional risk factors such as personal or family history of pre-syncope or syncope, electrolyte disturbances or cardiovascular disease. Elderly male patients are also subject to QTc interval prolongation when such risk factors are present. It is important that the clinicians themselves inspect ECGs. If the QT interval is more than half the RR interval, QTc interval prolongation is likely to be present. In such cases, a cardiology colleague interested in QTc interval issues and TdP should be asked to review the ECG. Finally, nothing in our recommendations replaces meticulous attention to US FDA guidelines in the package insert of each drug. [ABSTRACT FROM AUTHOR]

Background: Irrigated radiofrequency (RF) ablation catheters may produce different lesion sizes dependent upon the electrode orientation to the tissue. This study examined the effect of irrigated electrode orientation on the lesion size and explores a potential mechanism for this effect. Methods and Results: Lesions were created in isolated porcine myocardium using an open irrigation, closed irrigation, and nonirrigated RF catheter (all 3.5-4 mm tips). Lesions were created with the electrodes with all permutations of electrode orientation (vertical or horizontal), contact pressure (6 or 20 g), and saline superfusate flow (0.2 or 0.4 m/sec) over tissue interface. The effect of electrode irrigation without RF delivery on tissue temperature was assessed with intramyocardial temperature probes and infrared thermal imaging. For both irrigated catheters, the horizontal orientation produced 25-30% smaller lesion volumes than the vertical orientation despite equal or greater power deliveries. The horizontal orientation produced larger lesion volumes for the nonirrigated catheter. Higher superfusate flow rates were associated with decreased lesion volumes for the irrigated catheters but greater lesion volumes for the nonirrigated catheter. Catheter irrigation alone without RF delivery reduced intramyocardial temperatures up to 4.9°C and the horizontal orientation produced a 2-fold greater area of tissue cooling than the vertical orientation. Conclusion: Horizontal electrode orientations reduce lesion volumes for irrigated RF catheters. This effect may be in part due to greater areas of active tissue cooling in the horizontal orientation. [ABSTRACT FROM AUTHOR]

AIMS: This feasibility trial evaluated the use, safety, and short-term benefits of a home-based exercise intervention designed to increase physical activity among adults with diabetes. METHODS: Participants with type 2 diabetes in a group practice were recruited and randomly assigned to the home-based exercise intervention or usual care. Participants were given diabetes self-management education, instructed to exercise 30 min 5 days/week, and were followed for 3 months. The intervention contained three exercise routines (aerobic and resistance exercises). Outcomes included changes from baseline at 3 months between groups in body mass index (BMI), quality of life, A1C, and blood pressure. RESULTS: Seventy-six sedentary adults completed the study: 49% intervention group, 68% women, 47% black, mean age 56.6+/-9.6 years. Using intention to treat analysis, a trend towards improvement between groups for BMI (mean change -0.4 versus 0.1, respectively; P=0.06) was identified. Thirty-eight percent of the intervention group adhered to 80% of the exercise recommendation and significantly improved BMI (-1.07; P<0.05). No other differences were detected between groups. CONCLUSIONS: Home-based exercise interventions have potential to reduce BMI in patients with diabetes. The results provide variance estimates necessary to power a larger study of longer duration. [ABSTRACT FROM AUTHOR]

While marketing is important and challenging for libraries of all types, librarians receive little formal training in this area. When minimal time, money, staff, and resources are invested in promoting a newly acquired resource, it is not surprising that the impact of the marketing is unclear. The purpose of this case study is to share the experience, sample materials, and lessons learned from involving a wide range of library staff in the implementation and marketing of Ex LibrisTM SFX® OpenURL technology at the Weill Cornell Medical Library. [ABSTRACT FROM AUTHOR]

Lack of adherence to prescribed antihypertensive regimens constitutes a barrier to adequate blood pressure control and prevention of cardiovascular events. Various means of measuring adherence to antihypertensive medications are currently available for use in clinical practice. The choice of the specific measure used in clinical practice depends on the intended use of the information, the resources available to the provider, as well as patient acceptance and convenience of the method. This article presents an overview of the advantages and limitations of the methods used to measure medication adherence that are currently available for use in outpatient settings, it also outlines provider strategies for addressing adherence issues related to antihypertensive medications.Indirect methods used to measure adherence in the outpatient setting include self report, electronic adherence monitoring (e.g. medication event monitoring system), pharmacy refill rates, and pill counts. Direct methods include the use of bioassays or biomarkers, which involve laboratory detection of the drug or a metabolic product of the drug in a biologic fluid, or laboratory detection of a biologic marker. Direct observation of the patient taking the medication is also another direct method; however, it is impractical in the outpatient setting, especially for long-term treatment. Each of these methods has advantages and disadvantages; perhaps using a combination of methods may provide the most accurate assessment of adherence.The information gained from measurement of adherence can help to formulate recommendations for individual patients regarding necessary adjustments to their medication-taking behavior to achieve the optimum outcome. Part of the difficulty associated with achieving better medication adherence lies in the inherent complexity of medication-taking decisions and behavior and of relationships between patients, their healthcare providers, and often others involved in the patient's care, such as family members. Poor medication adherence and ultimately, adverse cardiovascular outcomes, is related to a variety of factors: quality of life; complexity of medication regimens; costs of medications; adverse effects of medications; demographic, behavioral, treatment and clinical variables; knowledge of hypertension and healthcare system issues; and use of non-conventional therapies. To be effective, strategies employed in clinical practice to overcome nonadherence need to take into account patients' individual characteristics. Frequently, more than one strategy is necessary to bring about the desired level of adherence. The benefits of proven medical treatments are only available to patients who actively use them; thus, patient adherence to healthcare provider recommendations is the key mediator between medical practice and health outcomes. [ABSTRACT FROM AUTHOR]

Weill Cornell Medical College in Qatar (WCMC-Q) was established in 2001. This case study describes the establishment and maintenance of access to licensed electronic resources from the libraries of Weill Cornell Medical College in New York City (WCMC-NY) and its parent institution, Cornell University in Ithaca, New York to the new and primarily digital WCMC-Q Distributed eLibrary (DeLib) in Doha, Qatar. Challenges in extending access included defining relationships in a way that vendors could understand, creating networks and support mechanisms on both sides, and communicating across logistical and cultural differences. Through collaboration and coordination, these separately funded libraries acquire and maintain access to electronic resources at a shared cost. [ABSTRACT FROM AUTHOR]

Context: Limited information exists to direct clinical management after an implantable device has been put under advisory. A better understanding of the risks and benefits of device replacement compared with continued clinical follow-up would be helpful to clinicians.Objective: Using the tools of decision analysis, to determine the best management approach (immediate device replacement vs continued monitoring) in the setting of a device advisory.Design: A decision model was constructed to evaluate the risks and benefits associated with immediate device replacement compared with continued monitoring.Main Outcome Measures: Variables considered included indications for device implantation, anticipated course following device failure, device failure rates from the advisory ranging from 0.0001% to 1.0% per year, and device replacement mortality rates ranging from 0.10% to 1.00% per procedure. Device replacement was preferred to continued follow-up when replacement led to greater patient survival.Results: The decision to replace a recalled device depends primarily on the advisory's estimated device failure rate and the likely effects of device failure on mortality. Procedural mortality is an important secondary factor, while patient age and remaining generator life have the least influence on the decision. For pacemaker-dependent patients, advisory device failure rates exceeding 0.3% warrant device replacement in most situations. In patients with implantable cardioverter-defibrillators for primary or secondary prevention, a failure rate associated with an advisory of 3.0% is needed to favor replacement in most cases, decreasing to close to 1.0% as procedural mortality rates decrease to 0.1% or risk of fatal arrhythmias increase to near 20% per year. In cases of pacemaker implantation for non-life-threatening situations (eg, carotid sinus hypersensitivity), most device advisories do not warrant device replacement.Conclusions: The decision to replace a device under advisory is determined primarily by the incidence of device malfunction and the likely effects of device failure. This analysis provides a framework for managing recalled devices in the context of device, patient, and institutional characteristics. [ABSTRACT FROM AUTHOR]

BACKGROUND: The sequence of atrial and ventricular electrograms following termination of ventricular pacing during supraventricular tachycardia has been shown to reliably differentiate atrial tachycardia from atrioventricular nodal reentrant tachycardia (AVNRT) and atrioventricular reentrant tachycardia (AVRT). However in patients with long HV intervals, this may be misleading due to a pseudo 'A-A-V' response. The aim of the present study is to see if inclusion of the timing of the His-bundle in the electrogram response (ER) following ventricular pacing would reliably identify the mechanism of tachycardia in patients with long HV intervals. METHODS: Eight patients (7 men) with AVNRT and underlying bundle branch block and long HV (>55 msec) intervals underwent ventricular pacing at 10-40 msec shorter than the tachycardia cycle length during SVT. The ER was classified as 'A-A-H' or 'A-H' depending on the number of atrial electrograms (A) prior to His deflection following VEP. RESULTS: The ER following ventricular pacing was classified as A-H in all 8 patients. However, using conventional classification the response was A-A-V in 5 of 8 patients due to delayed ventricular activation secondary to long HV intervals and would erroneously suggest atrial tachycardia. The ER was A-V in only 1 of 8 patients. In the remaining 2 patients the A and V electrograms were simultaneous. CONCLUSIONS: Incorporating the His-bundle in the ER following ventricular pacing would eliminate the pseudo 'A-A-V' response in patients with AVNRT and long HV intervals. Labeling the response to ventricular pacing as 'A-H' or 'A-A-H' is simple and more accurate. [ABSTRACT FROM AUTHOR]

INTRODUCTION: This study examined the relationship between dobutamine facilitation of ventricular tachyarrhythmia (VT) inducibility with programmed electrical stimulation (PES) and dobutamine stress-induced myocardial ischemia. METHODS AND RESULTS: Twenty patients with prior myocardial infarction and cardiac arrest or sustained VT but no sustained VT induced at baseline electrophysiologic testing underwent repeat PES during dobutamine infusion. Ischemia (new or worsened wall-motion abnormality) was documented by echocardiography performed in conjunction with PES. Eight patients were receiving Class I or III antiarrhythmic drugs and seven beta-blockers. Dobutamine facilitated induction of sustained VT in 16 patients (80%) and provoked ischemia in 13 patients (65%). Induction of VT was associated with ischemia in 9 patients (56%). VTs associated with ischemia were induced at higher dobutamine doses (26 +/- 11 vs 11 +/- 10 microg/kg per min, P = 0.02) than were VTs without ischemia (n = 7). Among 13 patients with provoked ischemia, 9 (69%) had VTs induced and 4 remained noninducible. The onset of ischemia occurred at the same dose as induction of VT in 5 patients and at a lower dose in 4 patients. Monomorphic VT (318 +/- 59 ms) was induced in 13 patients, of whom 8 (62%) had ischemia. The ECG morphology of VT suggested an origin in a myocardial segment that demonstrated initial viability at low doses then ischemic dysfunction at higher doses preceding VT induction in 7 (88%) of 8 patients. CONCLUSION: Dobutamine enhances inducibility of sustained VTs during PES. The temporal and anatomic association of dobutamine-induced ischemia and VT suggests that at high dobutamine doses, ischemia may contribute to ventricular arrhythmia inducibility in some patients. [ABSTRACT FROM AUTHOR]

Assessing the impact of clinically relevant quality improvement activities (QIA) is important to managed care organizations; yet, turnover in enrollment can reduce the data available for analyses, thus decreasing the chance that a difference post-QIA will be detected. The Combined Quality Improvement Ratio (CQuIR) uses matching of patients into pairs pre- and post-QIA to systematically and validly increase the data included in the analysis for evaluation of the QIA. Using a paired cohort study design, 456 pairs of patients with diabetes were identified using the Health Plan Employer Data Information Set (HEDIS) specifications. Patients having retinal examinations were identified pre- and post-QIA. The change in retinal examination rates was analyzed and results compared using repeated pairs (RP), matched pairs (MP), and combined pairs (CP). The CQuIR methodology (which uses CP = RP + MP) resulted in an increase in sample size (n = 456 [CP] versus n = 156 [RP] and n = 300 [MP]) and consequently an increase in power (0.92 [CP] versus 0.38 [RP] and 0.82 [MP]) and a decrease in the confidence interval range (0.97 [CP] versus 2.06 [RP] and 1.14 [MP]). The CQuIR uses a statistically valid approach to increase the data available for the evaluation of QIAs. [ABSTRACT FROM AUTHOR]

Implantable cardioverter defibrillators (ICDs) with dual chamber and duo! chamber rate responsive pacing may offer hemodynamic advantages for some ICD patients. Separate ICDs and DDDR pacemakers can result in device to device interactions, inappropriate shocks, and underdetection of ventricular fibrillation (VF). The objectives of this study were to compare the VF detection times between the Ventak AV II DB and the Ventak AV during high rate DDDR and DDD pacing and to test the safety of dynamic ventricular refractory period shortening. Patients receiving an ICD were randomized in a paired comparison to pacing at 150 beats/min (DDD pacing) or 175 beats/min (DDDR pacing) during ICD threshold testing to create a 'worst case scenario' for VF detection. The VF detection rate was set to 180 beats/min. and VF was induced during high rate pacing with alternating current. The device was then allowed to detect and treat VF. The induction was repeated for each patient at each programmed setting so that all patients were tested at both programmed settings. Paired analysis was performed. Patient characteristics were a mean age of 69 ± 11 years, 78% were men, coronary artery disease was present in 85%, and a mean left ventricular ejection fraction of 0.34 ± 0.11. Fifty-two episodes of VF were induced in 26 patients. Despite the high pacing rate, all VF episodes were appropriately detected. The mean VF detection time was 2.4 ± 1.0 seconds during DDD pacing and 2.9 ± 1.9 seconds during DDDH pacing (P - NS). DDD and DDDR programming resulted in appropriate detection of all episodes of VF with similar detection times despite the 'worst case scenario' tested. Delays in detection may be seen with long programmed ventricular refractory periods which shorten the VF sensing window and may be avoided with dynamic ventricular refractory period shortening. [ABSTRACT FROM AUTHOR]

The increasing use of composite materials in new aircraft builds leads to a significant demand for titanium alloy structural parts. The increasing costs and popularity of this material, together with restrictions in supply and processing, are driving the aerospace industry to make increasingly efficient use of available material. Linear Friction Welding (LFW) is a rapid, high integrity, solid-state forging process that has the potential to decrease the buy-to-fly ratio, production time and time to market of aerostructure components. Its dependability has already been proven for the production of key components in some of the latest generation aero engines. The LFW process is yet to be used for aerostructures. This is primarily due to the LFW process not being widely known, but also due to a lack of performance data on aerostructures manufactured by LFW being available to the supply chain and design community. To address this issue, a large series of titanium alloy weldments was produced and assessed via metallographic examinations and mechanical testing in both as-welded and post-weld heat-treated condition. The matrix of experiments was able to capture the LFW process window of this titanium alloy, and to measure the impact of the parametric conditions. Metallographic examination revealed a high integrity weld free from contaminants and oxides at the weld interface; with a characteristic recrystallised Widmanstätten martensitic Beta weld centre zone microstructure, in as welded condition, and a finegrained equiaxed recrystallised to alpha-beta microstructure in post-weld heat-treated condition. As-welded joints were tested under tensile and alternating fatigue conditions to provide an extended set of joint performance data. Joints demonstrated tensile performance equivalent to that of the parent material in all cases, with near-parent fatigue properties and improved (reduced) fatigue scatter in the post-weld heat-treated condition.

Control of heart rate in critically ill patients who develop atrial fibrillation or atrial flutter can be difficult. Amiodarone may be an alternative agent for heart rate control if conventional measures are ineffective. We retrospectively studied intensive care unit patients (n = 38) who received intravenous amiodarone for heart rate control in the setting of hemodynamically destabilizing atrial tachyarrhythmias resistant to conventional heart rate control measures. Atrial fibrillation was present in 33 patients and atrial flutter in 5 patients. Onset of rapid heart rate (mean 149 +/- 13 beats/min) was associated with a decrease in systolic blood pressure of 20 +/- 5 mm Hg (p <0.05). Intravenous diltiazem (n = 34), esmolol (n = 4), or digoxin (n = 24) had no effect on heart rate, while reducing systolic blood pressure by 6 +/- 4 mm Hg (p <0.05). The infusion of amiodarone (242 +/- 137 mg over 1 hour) was associated with a decrease in heart rate by 37 +/- 8 beats/min and an increase in systolic blood pressure of 24 +/- 6 mm Hg. Both of these changes were significantly improved (p <0.05) from onset of rapid heart rate or during conventional therapy. Beneficial changes were also noted in pulmonary artery occlusive pressure and cardiac output. There were no adverse effects secondary to amiodarone therapy. Intravenous amiodarone is efficacious and hemodynamically well tolerated in the acute control of heart rote in critically ill patients who develop atrial tachyarrhythmias with rapid ventricular response refractory to conventional treatment. Cardiac electrophysiologic consultation should be obtained before using intravenous amiodarone for this purpose. [ABSTRACT FROM AUTHOR]

OBJECTIVE To examine the effects of crossing over from optimized multiple daily injection (MDI) therapy to sensor-augmented pump (SAP) therapy for 6 months, and the effects of 18 months' sustained use of SAP. RESEARCH DESIGN AND METHODS The 6-month, single-crossover continuation phase of Sensor-Augmented Pump Therapy for A1C Reduction (STAR 3) provided SAP therapy to 420 subjects who completed the 1-year randomized study. The primary outcome was change in A1C in the crossover group. RESULTS A1C values were initially lower in the continuing-SAP group than in the crossover group (7.4 vs. 8.0%, P < 0.001). A1C values remained reduced in the SAP group. After 3 months on the SAP system, A1C decreased to 7.6% in the crossover group (P < 0.001); this was a significant and sustained decrease among both adults and children (P < 0.05). CONCLUSIONS Switching from optimized MDI to SAP therapy allowed for rapid and safe A1C reductions. Glycemic benefits of SAP therapy persist for at least 18 months. [ABSTRACT FROM AUTHOR]