The importance of methods for site performance evaluation in REPRIEVE, a longitudinal, global, multicenter trial.

BACKGROUND: REPRIEVE, the Randomized Trial to Prevent Vascular Events in HIV, is a multicenter, primary prevention trial evaluating whether a statin can prevent major cardiovascular events in people with HIV. REPRIEVE is conducted at >100 clinical research sites (CRSs) globally. Detailed, comprehensive, and novel methods for evaluating and communicating CRS performance are required to ensure trial integrity and data quality. In this analysis we describe a comprehensive multidimensional methodology for evaluating CRS performance. METHODS: The REPRIEVE Data Coordinating and Clinical Coordinating Centers developed a robust system for evaluation of and communication with CRSs, designed to identify potential issues and obstacles to performance, provide real-time technical support, and make recommendations for process improvements to facilitate efficient trial execution. We describe these systems and evaluate their impact on participant retention, data management, and specimen management from 2019 to 2022, corresponding to the period from end of recruitment to present. This evaluation was based on pre-defined metrics, regular reviews, and bidirectional communication. RESULTS: Participant retention, data management, and specimen management all remained steady over the three-year period, although metrics varied by country of enrollment. Targeted messaging relating to certain performance metrics was effective. CONCLUSION: Site performance is vital to ensure trial integrity and achievement of key trial goals. This analysis demonstrates that utilization of a comprehensive approach allows for a thorough evaluation of CRS performance, facilitates data and specimen management, and enhances participant retention. Our approach may serve as a guidepost for maximizing future large-scale clinical trials' operational success and scientific rigor. CLINICALTRIALS: gov Identifier: NCT02344290.

SenseCam: a wearable camera that stimulates and rehabilitates autobiographical memory.

SenseCam is a wearable digital camera that captures an electronic record of the wearer's day. It does this by automatically recording a series of still images through its wide-angle lens, and simultaneously capturing a log of data from a number of built-in electronic sensors. Subsequently reviewing a sequence of images appears to provide a powerful autobiographical memory cue. A preliminary evaluation of SenseCam with a patient diagnosed with severe memory impairment was extremely positive; periodic review of images of events recorded by SenseCam resulted in significant recall of those events. Following this, a great deal of work has been undertaken to explore this phenomenon and there are early indications that SenseCam technology may be beneficial to a variety of patients with physical and mental health problems, and is valuable as a tool for investigating normal memory through behavioural and neuroimaging means. Elsewhere, it is becoming clear that judicious use of SenseCam could significantly impact the study of human behaviour. Meanwhile, research and development of the technology itself continues with the aim of providing robust hardware and software tools to meet the needs of clinicians, patients, carers, and researchers. In this paper we describe the history of SenseCam, and the design and operation of the SenseCam device and the associated viewing software, and we discuss some of the ongoing research questions being addressed with the help of SenseCam.

SenseCam improves memory for recent events and quality of life in a patient with memory retrieval difficulties.

A wearable camera that takes pictures automatically, SenseCam, was used to generate images for rehearsal, promoting consolidation and retrieval of memories for significant events in a patient with memory retrieval deficits. SenseCam images of recent events were systematically reviewed over a 2-week period. Memory for these events was assessed throughout and longer-term recall was tested up to 6 months later. A written diary control condition followed the same procedure. The SenseCam review procedure resulted in significantly more details of an event being recalled, with twice as many details recalled at 6 months follow up compared to the written diary method. Self-report measures suggested autobiographical recollection was triggered by the SenseCam condition but not by reviewing the written diary. Emotional and social wellbeing questionnaires indicated improved confidence and decreased anxiety as a result of memory rehearsal using SenseCam images. We propose that SenseCam images provide a powerful boost to autobiographical recall, with secondary benefits for quality of life.

Design and Characterisation of Titanium Nitride Subarrays of Kinetic Inductance Detectors for Passive Terahertz Imaging.

We report on the investigation of titanium nitride (TiN) thin films deposited via atomic layer deposition (ALD) for microwave kinetic inductance detectors (MKID). Using our in-house ALD process, we have grown a sequence of TiN thin films (thickness 15, 30, 60 nm). The films have been characterised in terms of superconducting transition temperature T c , sheet resistance R s and microstructure. We have fabricated test resonator structures and characterised them at a temperature of 300 mK. At 350 GHz, we report an optical noise equivalent power NEP opt ≈ 2.3 × 10 - 15 W / Hz , which is promising for passive terahertz imaging applications.

Septic shock in chronic dialysis patients: clinical characteristics, antimicrobial therapy and mortality.

OBJECTIVES: To describe the clinical characteristics and in-hospital mortality of chronic dialysis-dependent end-stage kidney disease patients with septic shock in comparison to septic shock patients not receiving chronic dialysis. METHODS: Using an international, multicenter database, we conducted a retrospective analysis of data collected from 10,414 patients admitted to the intensive care unit (ICU) with septic shock from 1989 to 2013, of which 800 (7.7 %) were chronic dialysis patients. Data on demographic characteristics, sites of infection, microbial pathogens, antimicrobial usage patterns, and in-hospital mortality were aggregated and compared for chronic dialysis and non-dialysis patients. Multivariate time-varying Cox models with and without propensity score matching were constructed to determine the association between dialysis and in-hospital death. RESULTS: Septic shock secondary to central venous catheter infection, peritonitis, ischemic bowel, and cellulitis was more frequent in chronic dialysis patients. The isolation of resistant organisms (10.7 vs. 7.1 %; p = 0.005) and delays in receiving antimicrobials (6.0 vs. 5.0 h) were more common in chronic dialysis patients than in non-dialysis patients. Delayed appropriate antimicrobial therapy was associated with an increased risk of death in chronic dialysis patients (p < 0.0001). In-hospital death occurred in 54.8 and 49.0 % of chronic dialysis and non-dialysis patients, respectively. After propensity score matching, there was no difference in overall survival between chronic dialysis and non-dialysis patients, but survival in chronic dialysis patients decreased over time compared to non-dialysis patients. CONCLUSIONS: The demographic and clinical characteristics of chronic dialysis patients with septic shock differ from those of similar non-dialysis patients. However, there was no significant difference in mortality between the chronic dialysis and non-dialysis patients with septic shock enrolled in this analysis.

A passive terahertz video camera based on lumped element kinetic inductance detectors.

We have developed a passive 350 GHz (850 µm) video-camera to demonstrate lumped element kinetic inductance detectors (LEKIDs)--designed originally for far-infrared astronomy--as an option for general purpose terrestrial terahertz imaging applications. The camera currently operates at a quasi-video frame rate of 2 Hz with a noise equivalent temperature difference per frame of ∼0.1 K, which is close to the background limit. The 152 element superconducting LEKID array is fabricated from a simple 40 nm aluminum film on a silicon dielectric substrate and is read out through a single microwave feedline with a cryogenic low noise amplifier and room temperature frequency domain multiplexing electronics.

Origin of the endemic fern genus Diellia coincides with the renewal of Hawaiian terrestrial life in the Miocene.

The enigmatic fern genus Diellia, endemic to the Hawaiian archipelago, consists of five extant and one recently extinct species. Diellia is morphologically highly variable, and a unique combination of characters has led to several contrasting hypotheses regarding the relationship of Diellia to other ferns. A phylogenetic analysis of four chloroplast loci places Diellia within 'black-stemmed' rock spleenworts of the species-rich genus Asplenium, as previously suggested by W. H. Wagner. Using an external calibration point, we estimate the divergence of the Diellia lineage from its nearest relatives to have occurred at ca. 24.3 Myr ago matching an independent estimate for the renewal of Hawaiian terrestrial life (ca. 23 Myr ago). We therefore suggest that the ancestor of the Diellia lineage may have been among the first successful colonists of the newly emerging islands in the archipelago. Disparity between morphological and nucleotide sequence variation within Diellia is consistent with a recent rapid radiation. Our estimated time of the Diellia radiation (ca. 2 Myr ago) is younger than the oldest island of Kaua'i (ca. 5.1 Myr ago) but older than the younger major islands of Maui (ca. 1.3 Myr ago), Lana'i (ca. 1.3 Myr ago) and Hawaii (ca. 0.43 Myr ago).

The novel kinesin spindle protein (KSP) inhibitor SB-743921 exhibits marked activity in in vivo and in vitro models of aggressive large B-cell lymphoma.

The kinesin spindle protein (KSP) is a mitotic protein essential for cell cycle control and motility. SB-743921 (hereafter SB-921) is an inhibitor that selectively targets the ATP-binding domain of the KSP. The preclinical activity of SB-921 was evaluated in models of diffuse large B-cell lymphoma (DLBCL). The cytotoxicity of SB-921 was evaluated in a series of germinal center (GC-DLBCL) and post-germinal center (ABC-DLBCL) DLBCL cell lines and a murine lymphoma xenograft model. GC-DLBCL lines generally demonstrated greater sensitivity to SB-921. IC50 values ranged between 1 nM and 900 nM for GC-DLBCL compared to 1 nM to 10 µM for ABC lines. SB-921 demonstrated marked activity in a xenograft model of Ly-1 (GC-DLBCL). While SB-921 was relatively more active in GC derived cell lines, ABC-derived lines still underwent apoptosis at higher concentrations. These results demonstrate that SB-921 inhibits proliferation and induces apoptosis in both GC-DLBCL and ABC-DLBCL.

Navigated placement of iliac bolts: description of a new technique.

BACKGROUND CONTEXT: Image navigation has improved the safety and ability to perform complex spinal procedures where visibility is not optimal or anatomic deformity is present. Numerous published studies are available demonstrating its effectiveness in improved pedicle screw placement in complex multiplanar deformities. Studies have also demonstrated image navigation technology versatility; however, stabilization of the lumbopelvic junction with navigated iliac bolt fixation has not been reported. PURPOSE: To describe an innovative versatile application of image navigation technology in spine surgery. We examine the safety, accuracy, and effectiveness of navigated iliac bolt placement while minimizing challenges associated with current techniques. STUDY DESIGN: Case series. PATIENT SAMPLE: Five patients requiring lumbopelvic fixation for multiple indications, including lumbosacral pseudoarthrosis, complex sacral fracture patterns, compromised revision sacral fixation, and as an adjunct to degenerative deformity with multilevel fusion, underwent navigated iliac bolt placement. OUTCOME MEASURES: Accurate placement was verified using intraoperative computed tomography (CT) imaging using O-ARM (Medtronic, Inc.) after placement. METHODS: Five patients requiring lumbopelvic fixation have undergone navigated iliac bolt placement using Medtronic Stealth Station Treon in conjunction with the O-ARM (Medtronic, Inc.). A right percutaneous posterior superior iliac spine (PSIS) reference frame was placed at the superior lateral margin of the PSIS, and bilateral iliac bolts were placed via navigation using both the anatomic and traditional surgical techniques. Both techniques were performed without direct notch palpation and minimal soft-tissue exposure. Postplacement intraoperative CT imaging was obtained to confirm position and trajectory of the bolts using O-ARM (Medtronic, Inc.). RESULTS: Ten iliac bolts were successfully placed in five patients. Intraoperative CT demonstrated ideal iliac screw bone placement projecting within 2 cm over sciatic notch, between pelvic tables. With image navigation, both anatomic and traditional iliac bolt placement techniques were performed with less surgical exposure, no radiation exposure, and complete accuracy using image navigation techniques with a percutaneous reference frame. The percutaneous reference frame placed in the superior lateral PSIS did not cause any interference with our navigated trajectory or bolt. CONCLUSIONS: Image-navigated iliac fixation allows for safe and accurate placement of bilateral iliac bolts without PSIS percutaneous reference frame interference. Image guidance eliminates fluoroscopic radiation exposure and extensive soft-tissue dissection and facilitates both traditional and anatomic iliac bolt placement techniques.

Obesity in critical care.

PURPOSE OF REVIEW: To review literature germane to the care of critically ill obese patients with emphasis upon the pathophysiology of obesity and its impact on clinical management. RECENT FINDINGS: Obesity continues to be a health epidemic of the industrialized world, and is associated with substantial morbidity and mortality. Chronic obesity results in derangements in cardiovascular, respiratory and metabolic function. Drug administration may be effected depending on the lipophilicity of the molecule administered. The ability to gain vascular access is often impaired because of large body habitus and should be aided with ultrasound guidance. The fidelity of blood pressure monitoring can also be adversely affected, necessitating the use of direct intraarterial monitoring. SUMMARY: Obesity has pathophysiologic effects upon all major organ systems. A thorough knowledge of these effects and specific intensive care unit-related issues are necessary for clinicians to anticipate common complications and provide timely and effective treatment for the obese intensive care unit patient.

The use of a wearable camera, SenseCam, as a pictorial diary to improve autobiographical memory in a patient with limbic encephalitis: a preliminary report.

This case study describes the use of a wearable camera, SenseCam, which automatically captures several hundred images per day, to aid autobiographical memory in a patient, Mrs B, with severe memory impairment following limbic encephalitis. By using SenseCam to record personally experienced events we intended that SenseCam pictures would form a pictorial diary to cue and consolidate autobiographical memories. After wearing SenseCam, Mrs B plugged the camera into a PC which uploaded the recorded images and allowed them to be viewed at speed, like watching a movie. In the control condition, a written diary was used to record and remind her of autobiographical events. After viewing SenseCam images, Mrs B was able to recall approximately 80% of recent, personally experienced events. Retention of events was maintained in the long-term, 11 months afterwards, and without viewing SenseCam images for three months. After using the written diary, Mrs B was able to remember around 49% of an event; after one month with no diary readings she had no recall of the same events. We suggest that factors relating to rehearsal/re-consolidation may have enabled SenseCam images to improve Mrs B's autobiographical recollection.