A computer assisted navigation technique to perform bone tumor resection without dedicated software

Purpose: In oncological orthopedics, navigation systems are limited to use in specialized centers, because specific, expensive, software is necessary. To resolve this problem, we present a technique using general spine navigation software to resect tumors located in different segments. Materials and Methods: This technique requires a primary surgery during which screws are inserted in the segment where the bone tumor is; next, a CT scan of the entire segment is used as a guide in a second surgery where a resection is performed under navigation control. We applied this technique in four selected cases. To evaluate the procedure, we considered resolution obtained, quality of the margin and its control. Results: In all cases, 1 mm resolution was obtained; navigation allowed perfect control of the osteotomies, reaching the minimum wide margin when desired. No complications were reported and all patients were free of disease at follow-up (average 25.5 months). Conclusions: This technique allows any bone segment to be recognized by the navigation system thanks to the introduction of screws as landmarks. The minimum number of screws required is four, but the higher the number of screws, the greater the accuracy and resolution. In our experience, five landmarks, placed distant from one another, is a good compromise. Possible disadvantages include the necessity to perform two surgeries and the need of a major surgical exposure; nevertheless, in our opinion, the advantages of better margin control justify the application of this technique in centers where an intraoperative CT scanner, synchronized with a navigation system or a dedicated software for bone tumor removal were not available

Can we do better? A qualitative study in the East of England investigating patient experience and acceptability of using the faecal immunochemical test in primary care.

OBJECTIVES: The faecal immunochemical test (FIT) is increasingly used in UK primary care to triage patients presenting with symptoms and at different levels of colorectal cancer risk. Evidence is scarce on patients' views of using FIT in this context. We aimed to explore patients' care experience and acceptability of using FIT in primary care. DESIGN: A qualitative semi-structured interview study. Interviews were conducted via Zoom between April and October 2020. Transcribed recordings were analysed using framework analysis. SETTING: East of England general practices. PARTICIPANTS: Consenting patients (aged ≥40 years) who presented in primary care with possible symptoms of colorectal cancer, and for whom a FIT was requested, were recruited to the FIT-East study. Participants were purposively sampled for this qualitative substudy based on age, gender and FIT result. RESULTS: 44 participants were interviewed with a mean age 61 years, and 25 (57%) being men: 8 (18%) received a positive FIT result. Three themes and seven subthemes were identified. Participants' familiarity with similar tests and perceived risk of cancer influenced test experience and acceptability. All participants were happy to do the FIT themselves and to recommend it to others. Most participants reported that the test was straightforward, although some considered it may be a challenge to others. However, test explanation by healthcare professionals was often limited. Furthermore, while some participants received their results quickly, many did not receive them at all with the common assumption that 'no news is good news'. For those with a negative result and persisting symptoms, there was uncertainty about any next steps. CONCLUSIONS: While FIT is acceptable to patients, elements of communication with patients by the healthcare system show potential for improvement. We suggest possible ways to improve the FIT experience, particularly regarding communication about the test and its results

Clustering in surgical trials : database of intracluster correlations

PMID: 22217216 [PubMed - indexed for MEDLINE] PMCID: PMC3311136 Free PMC ArticlePeer reviewedPublisher PD

Case Study 3: Movement Lawyers and Community Organizers in Litigation: Issues of Finances and Collaboration

This essay represents one of several Case Studies published as the Movement Lawyering Roundtable Symposium by Hofstra Law Review. The Case Studies were developed within a roundtable of movement lawyers, community organizers, and legal ethics experts convened in March, 2018 by the Monroe H. Freedman Institute for the Study of Legal Ethics at Hofstra University’s Maurice A. Deane School of Law. This Case Study addresses the ethical tensions encountered by movement lawyers and community organizers engaged in public interest litigation. The Study consists of three topics, with resulting ethics analyses of the issues that arise in the differing settings. The first involves questions of financing the broad work of a community organizing client, while honoring the mandates of the rule of professional conduct prohibiting a lawyer from offering financial assistance to clients in litigation. The second issue addressed how lawyers might share attorneys’ fees awards with community groups who are ongoing clients. The third issue pivots to questions of how movement lawyers might counsel community organizations about disagreements with other pro bono lawyers representing the clients. Each of these sets of legal ethics issues arises in movement lawyering practice, and can be confounding. This essay seeks to offer guidance to lawyers navigating these sometimes delicate ethical waters

Diagnostic accuracy of Doppler ultrasound technique of the penile arteries in correlation to selective arteriography

In 63% of 265 patients with erectile dysfunction a relevant arterial inflow disturbance was found by Doppler ultrasound examination. Correlation between Doppler and arteriography in 58 patients showed an accuracy of 95% in detecting penile arteries and an accuracy of 91% in discovering a pathological arterial pattern (arterial anomaly or arteriosclerotic obstruction). In 15 patients the arterial inflow was measured additionally by Doppler ultrasound technique after intracavernosal injection of vasoactive drugs (IIVD) (7.5 mg papaverine and 0.25 mg phentolamine). This technique proved to be more reliable than in the flaccid state and markedly facilitated localization and assessment of pathological changes of the cavernosal arteries

Seebeck Effect in Magnetic Tunnel Junctions

Creating temperature gradients in magnetic nanostructures has resulted in a new research direction, i.e., the combination of magneto- and thermoelectric effects. Here, we demonstrate the observation of one important effect of this class: the magneto-Seebeck effect. It is observed when a magnetic configuration changes the charge based Seebeck coefficient. In particular, the Seebeck coefficient changes during the transition from a parallel to an antiparallel magnetic configuration in a tunnel junction. In that respect, it is the analog to the tunneling magnetoresistance. The Seebeck coefficients in parallel and antiparallel configuration are in the order of the voltages known from the charge-Seebeck effect. The size and sign of the effect can be controlled by the composition of the electrodes' atomic layers adjacent to the barrier and the temperature. Experimentally, we realized 8.8 % magneto-Seebeck effect, which results from a voltage change of about -8.7 {\mu}V/K from the antiparallel to the parallel direction close to the predicted value of -12.1 {\mu}V/K.Comment: 16 pages, 7 figures, 2 table

Mutations in protocadherin 15 and cadherin 23 affect tip links and mechanotransduction in mammalian sensory hair cells

Immunocytochemical studies have shown that protocadherin-15 (PCDH15) and cadherin-23 (CDH23) are associated with tip links, structures thought to gate the mechanotransducer channels of hair cells in the sensory epithelia of the inner ear. The present report describes functional and structural analyses of hair cells from Pcdh15av3J (av3J), Pcdh15av6J (av6J) and Cdh23v2J (v2J) mice. The av3J and v2J mice carry point mutations that are predicted to introduce premature stop codons in the transcripts for Pcdh15 and Cdh23, respectively, and av6J mice have an in-frame deletion predicted to remove most of the 9th cadherin ectodomain from PCDH15. Severe disruption of hair-bundle morphology is observed throughout the early-postnatal cochlea in av3J/av3J and v2J/v2J mice. In contrast, only mild-to-moderate bundle disruption is evident in the av6J/av6J mice. Hair cells from av3J/av3J mice are unaffected by aminoglycosides and fail to load with [3H]-gentamicin or FM1-43, compounds that permeate the hair cell's mechanotransducer channels. In contrast, hair cells from av6J/av6J mice load with both FM1-43 and [3H]-gentamicin, and are aminoglycoside sensitive. Transducer currents can be recorded from hair cells of all three mutants but are reduced in amplitude in all mutants and have abnormal directional sensitivity in the av3J/av3J and v2J/v2J mutants. Scanning electron microscopy of early postnatal cochlear hair cells reveals tip-link like links in av6J/av6J mice, substantially reduced numbers of links in the av3J/av3J mice and virtually none in the v2J/v2J mice. Analysis of mature vestibular hair bundles reveals an absence of tip links in the av3J/av3J and v2J/v2J mice and a reduction in av6J/av6J mice. These results therefore provide genetic evidence consistent with PCDH15 and CDH23 being part of the tip-link complex and necessary for normal mechanotransduction

Targeted Drug Delivery by Gemtuzumab Ozogamicin: Mechanism-Based Mathematical Model for Treatment Strategy Improvement and Therapy Individualization

Gemtuzumab ozogamicin (GO) is a chemotherapy-conjugated anti-CD33 monoclonal antibody effective in some patients with acute myeloid leukemia (AML). The optimal treatment schedule and optimal timing of GO administration relative to other agents remains unknown. Conventional pharmacokinetic analysis has been of limited insight for the schedule optimization. We developed a mechanism-based mathematical model and employed it to analyze the time-course of free and GO-bound CD33 molecules on the lekemic blasts in individual AML patients treated with GO. We calculated expected intravascular drug exposure (I-AUC) as a surrogate marker for the response to the drug. A high CD33 production rate and low drug efflux were the most important determinants of high I-AUC, characterizing patients with favorable pharmacokinetic profile and, hence, improved response. I-AUC was insensitive to other studied parameters within biologically relevant ranges, including internalization rate and dissociation constant. Our computations suggested that even moderate blast burden reduction prior to drug administration enables lowering of GO doses without significantly compromising intracellular drug exposure. These findings indicate that GO may optimally be used after cyto-reductive chemotherapy, rather than before, or concomitantly with it, and that GO efficacy can be maintained by dose reduction to 6 mg/m2 and a dosing interval of 7 days. Model predictions are validated by comparison with the results of EORTC-GIMEMA AML19 clinical trial, where two different GO schedules were administered. We suggest that incorporation of our results in clinical practice can serve identification of the subpopulation of elderly patients who can benefit most of the GO treatment and enable return of the currently suspended drug to clinic

miR-96 regulates the progression of differentiation in mammalian cochlear inner and outer hair cells

MicroRNAs (miRNAs) are small noncoding RNAs able to regulate a broad range of protein-coding genes involved in many biological processes. miR-96 is a sensory organ-specific miRNA expressed in the mammalian cochlea during development. Mutations in miR-96 cause nonsyndromic progressive hearing loss in humans and mice. The mouse mutant diminuendo has a single base change in the seed region of the Mir96 gene leading to widespread changes in the expression of many genes. We have used this mutant to explore the role of miR-96 in the maturation of the auditory organ. We found that the physiological development of mutant sensory hair cells is arrested at around the day of birth, before their biophysical differentiation into inner and outer hair cells. Moreover, maturation of the hair cell stereocilia bundle and remodelling of auditory nerve connections within the cochlea fail to occur in miR-96 mutants. We conclude that miR-96 regulates the progression of the physiological and morphological differentiation of cochlear hair cells and, as such, coordinates one of the most distinctive functional refinements of the mammalian auditory system