Search

Hodgkin lymphoma (HL) patients who relapse after autologous-stem-cell- transplantation (auto-SCT) have traditionally had a poor prognosis. We analyzed 1781 adult HL patients who relapsed between 2006 and 2017 after a first auto-SCT. The 4-year overall survival (OS) after relapse continuously increased from 32% for patients relapsing in 2006-2008, to 63% for patients relapsing in 2015-2017 (p = 0.001). The improvement over time was predominantly noted in patients who had an early relapse (within 12 months) after auto-SCT (p = 0.01). On multivariate analysis, patients who relapsed in more recent years and those with a longer interval from transplant to relapse had a better OS, whereas increasing age, poor performance status, bulky disease, extranodal disease and presence of B symptoms at relapse were associated with a worse OS. Brentuximab vedotin (BV), checkpoint inhibitors (CPI) and second transplant (SCT2; 86% allogeneic) were used in 233, 91 and 330 patients respectively. The 4-year OS from BV, CPI, and SCT2 use was 55%, 48% and 55% respectively. In conclusion, the outcome after post-transplant relapse has improved significantly in recent years, particularly in the case of early relapse. These large-scale real-world data can serve as benchmark for future studies in this setting.

Purpose The role of chemotherapy (CT) and radiotherapy (RT) for management of extraskeletal osteosarcoma (ESOS) remains controversial. We examined disease outcomes for ESOS patients and investigated the association between CT/RT with recurrence and survival. Patients and methods Retrospective review at 25 international sarcoma centers identified patients ≥18 years old treated for ESOS from 1971 to 2016. Patient/tumour characteristics, treatment, local/systemic recurrence, and survival data were collected. Kaplan–Meier survival and Cox proportional-hazards regression and cumulative incidence competing risks analysis were performed. Results 370 patients with localized ESOS treated definitively with surgery presented with mainly deep tumours (n = 294, 80%). 122 patients underwent surgical resection alone, 96 (26%) also received CT, 70 (19%) RT and 82 (22%) both adjuvants. Five-year survival for patients with localized ESOS was 56% (95% CI 51%–62%). Almost half of patients (n = 173, 47%) developed recurrence: local 9% (35/370), distant 28% (102/370) or both 10% (36/370). Considering death as a competing event, there was no significant difference in cumulative incidence of local or systemic recurrence between patients who received CT, RT, both or neither (local p = 0.50, systemic p = 0.69). Multiple regression Cox analysis showed a significant association between RT and decreased local recurrence (HR 0.46 [95% CI 0.26–0.80], p = 0.01). Conclusion Although the use of RT significantly decreased local recurrences, CT did not decrease the risk of systemic recurrence, and neither CT, nor RT nor both were associated with improved survival in patients with localized ESOS. Our results do not support the use of CT; however, adjuvant RT demonstrates benefit in patients with locally resectable ESOS.

The treatment of sarcoma necessitates a collaborative approach, given its rarity and complex management. At a single institution, multidisciplinary teams of specialists determine and execute treatment plans involving surgical, radiation, and medical management. Treatment guidelines for systemic therapies in advanced or nonresectable soft tissue sarcoma have advanced in recent years as new immunotherapies and targeted therapies become available. Collaboration between institutions is necessary to facilitate accrual to clinical trials. Here, we describe the success of the Midwest Sarcoma Trials Partnership (MWSTP) in creating a network encompassing large academic centers and local community sites. We propose a new model utilizing online platforms to expand the reach of clinical expertise for the treatment of advanced soft tissue sarcoma.

We profiled the gene regulatory landscape of Brassica napus reproductive development using RNA sequencing. Comparative analysis of this nascent amphidiploid across the plant lifecycle revealed the contribution of each subgenome to plant reproduction. Global mRNA profiling revealed lower accumulation of Cn subgenome transcripts relative to the An subgenome. Subgenome-specific transcriptional networks identified distinct transcription factor families enriched in each of the An and Cn subgenome early in seed development. Global gene expression profiling of laser-microdissected seed subregions further reveal subgenome expression dynamics in the embryo, endosperm, and seed coat of early stage seeds. Transcription factors predicted to be regulators encoded by the An subgenome are expressed primarily in the seed coat whereas regulators encoded by the Cn subgenome were expressed primarily in the embryo. Data suggest subgenome bias are characteristic features of the B. napus seed throughout development, and that such bias might not be universal across the embryo, endosperm, and seed coat of the developing seed. Whole genome transcription factor networks identified BZIP11 as a transcriptional regulator of early B. napus seed development. Knockdown of BZIP11 using RNA interference resulted in a similar reduction in gene activity of predicted gene targets, and a reproductive-lethal phenotype. Taken together, transcriptional networks spanning both the An and Cn genomes of the B. napus seed can identify valuable targets for seed development research and that-omics level approaches to studying gene regulation in B. napus can benefit from both broad and high-resolution analyses.One Sentence SummaryGlobal RNA sequencing coupled with laser microdissection provides a critical resource to study subgenome bias in whole seeds and specific tissues of polyploid plants.

Injuries to the hand and wrist are common and account for a significant amount of emergency department presentations. The burden placed on the individual, community and society as a result of these injuries can be substantial; however, the actual cost of these injuries in Australia is mostly unknown. Using various methods, this research found that these injuries have the potential to lead to substantial costs and impacts on the individual patient, their families, the workplace, the public health system and broader society in Australia. Recommendations for reducing the burden at the individual, workplace, health system levels, and society are provided.

PURPOSE This study evaluates the correlation between corneal densitometry and epithelial ingrowth (EI) after laser in situ keratomileusis (LASIK). METHODS Corneal densitometry of 3 patients who developed EI after LASIK was measured with the Oculus Pentacam. Corneal densitometry readings of each patient were obtained preoperatively and postoperatively after ingrowth was discovered. Densitometry was recorded at the central nest of opacity and at the leading edges of EI. RESULTS For all patients, the most severe stages of EI observed on slit-lamp photographs correlated with the highest densitometry readings, with peak densitometry ranging from 73.3 to 95.1. These values were much higher than preoperative densitometry readings, which ranged from 21.8 to 27.2. In 2 cases, the Pentacam densitometry map revealed progression of EI toward the visual axis that was only faintly detectable or not detectable at all on the corresponding slit-lamp photographs. CONCLUSIONS Corneal densitometry seems to be an objective measure of the severity and progression of EI after LASIK.

Academic medical centers (AMCs) today prioritize digital innovation. In efforts to develop and disseminate the best technology for their institutions, challenges arise in organizational structure, cross-disciplinary collaboration, and creative and agile problem solving that are essential for successful implementation. To address these challenges, the Digital DesignLab was created at NYU Langone Health to provide structured processes for assessing and supporting the capacity for innovative digital development in our research and clinical community. Digital DesignLab is an enterprise level, multidisciplinary, digital development team that guides faculty and student innovators through a digital development “pipeline”, which consists of intake, discovery, bootcamp, development. It also provides a framework for digital health innovation and dissemination at the institution. This paper describes the Digital DesignLab’s creation and processes, and highlights key lessons learned to support digital health innovation at AMCs.

This article examines the limited Europeanization of contemporary Portuguese security policy and highlights how the persistence of North Atlantic Treaty Organisation (NATO) and the emergence of the Lusophone world have shaped Portuguese participation in the European Union's (EU's) Common Foreign and Security Policy in recent years, particularly in Common Security and Defence Policy (CSDP) missions in Africa and in the European Defence Agency's co-operation activities. Europeanization's conceptual weaknesses, combined with the mutually reinforcing nature of transatlantic, EU and Lusophone security co-operation, have reinforced the ambiguous nature of what a “Europeanized” vision for European security might look like, especially given long-standing loyalties to NATO. This affords states considerable margin for manoeuvrability in defining their security priorities, so long as they are seen as being broadly consistent. This article reassesses the appropriateness of the Europeanization concept and show...

A variety of analytical approaches have indicated that melanoma cell line UCLA‐SO‐M14 (M14) and breast carcinoma cell line MDA‐MB‐435 originate from a common donor. This indicates that at some point in the past, one of these cell lines became misidentified, meaning that it ceased to correspond to the reported donor and instead became falsely identified (through cross‐contamination or other means) as a cell line from a different donor. Initial studies concluded that MDA‐MB‐435 was the misidentified cell line and M14 was the authentic cell line, although contradictory evidence has been published, resulting in further confusion. To address this question, we obtained early samples of the melanoma cell line (M14), a lymphoblastoid cell line from the same donor (ML14), and donor serum preserved at the originator's institution. M14 samples were cryopreserved in December 1975, before MDA‐MB‐435 cells were established in culture. Through a series of molecular characterizations, including short tandem repeat (STR) profiling and cytogenetic analysis, we demonstrated that later samples of M14 and MDA‐MB‐435 correspond to samples of M14 frozen in 1975, to the lymphoblastoid cell line ML14, and to the melanoma donor's STR profile, sex and blood type. This work demonstrates conclusively that M14 is the authentic cell line and MDA‐MB‐435 is misidentified. With clear provenance information and authentication testing of early samples, it is possible to resolve debates regarding the origins of problematic cell lines that are widely used in cancer research., What's new? A variety of analytical approaches have indicated that melanoma cell line M14 and breast carcinoma cell line MDA‐MB‐435 originate from a common donor, but there is ongoing debate regarding which is the misidentified cell line. Here, authentication testing of M14 from 1975 (prior to the establishment of MDA‐MB‐435), with comparison to donor serum and lymphoblastoid cell line ML14, shows that M14 is the authentic cell line and MDA‐MB‐435 is a misidentified derivative. With clear provenance information and authentication testing of early samples, debates regarding the origins of problematic cell lines that are widely used in cancer research can be resolved.

A novel plasma-assisted desorption/ionization (PADI) method that can be coupled with atmospheric pressure sampling mass spectrometry to yield mass spectral information under ambient conditions of pressure and humidity from a range of surfaces without the requirement for sample preparation or additives is reported. PADI is carried out by generating a nonthermal plasma which interacts directly with the surface of the analyte. Desorption and ionization then occur at the surface, and ions are sampled by the mass spectrometer. The PADI technique is demonstrated and compared with desorption electrospray ionization (DESI) for the detection of active ingredients in a range of over-the-counter and prescription pharmaceutical formulations, including nonsterodial anti-inflammatory drugs (mefenamic acid, Ibugel, and ibuprofen), analgesics (paracetamol, Anadin Extra), and Beecham's "all in one" cold and flu remedy. PADI has also been successfully applied to the analysis of nicotine in tobacco and thiosulfates in garlic. PADI experiments have been performed using a prototype source interfaced with a Waters Platform LCZ single-quadrupole mass spectrometer with limited modifications and a Hiden Analytical HPR-60 molecular beam mass spectrometer (MBMS). The ability of PADI to rapidly detect active ingredients in pharmaceuticals without the need for prior sample preparation, solvents, or exposed high voltages demonstrates the potential of the technique for high-throughput screening in a pharmaceutical or forensic environment.

Commentators have frequently noted that a sentence spoken by Agathon early in the Symposium appears to set up some kind of a contest of wisdom between himself and Socrates, with Dionysos named as judge.1 The narrator reports the relevant passage as part of some polite banter during which both characters protest the other’s greater wisdom: ‘IbristOw e‰’, ¶fh, ‘Œ S≈kratew’, i EAgayvn. ‘ka‹ taEta m¢n ka‹ Ul¤gon Isteron diadikasOmeya §g≈ te ka‹ sA per‹ t∞w sof¤aw, dikasta xr≈menoi t“ DionEsƒ: nEn d¢ prUw tU de›pnon pr«ta tr°pou.’ (175e7-10) ‘Enough of your sarcasm, Socrates,’ replied Agathon. ‘We’ll settle our respective claims to wisdom a little later on, and Dionysus, the god of wine, shall judge between us; for the moment give your attention to your dinner.’2 There is, however, considerable disagreement concerning the nature and the significance of this contest. Some commentators, taking their cue from the celebratory occasion for Agathon’s drinking-party (his first victory as a tragic poet), infer that Plato must be hinting at a contest of poetic skill analogous to the one Agathon had just won, but now with Socrates/Plato as his chief competitor; on this interpretation, Plato would be using this device to position himself as a poet (i.e., author of dialogues) in competition with the tragedians (e.g., Bacon 1959, Anton 1962, Clay 1983, Sider 1980, Gould 1990, and Usher 2002). Other commentators read it instead as a version of the ‘ancient quarrel between poetry and philosophy’ mentioned by Plato at Republic 607b (e.g., Kruger 1963 and Rosen1987). For others, Plato has indicated no more than a comparison of the personal wisdom of these two characters (e.g., Anderson 1993, esp. 115-116). Most of these commentators have further suggested that the passage functions as a framing device for what follows, namely, the speeches about Eros. The existence of such a framing function would appear to be guaranteed by the now widely recognized role of the drunken Alcibiades as an image of Dionysos.3 Ancient Philosophy 24 (2004) ©Mathesis Publications 81

Recently we reported the use of octamer primers tailed with 5-nitroindole for use as primers in cycle sequencing reactions. Here we report the successful use of some other universal base analogues to improve the effectiveness of an octamer sequencing primer. These analogues are 5-nitroindazole, 3-nitropyrrole and benzimidazole.

The essay presents a summary of views of the most salient ancient philosophers on the nature of the good life and tries to connect them to contemporary research on the quality of life.

Highly oriented pyrolytic graphite (HOPG) has been studied by several groups as an electrode material, due mainly to its well-defined surface structure compared to more commonly used materials such as glassy carbon. The basal plane of HOPG is also a common standard for scanning tunneling microscopy because it is atomically flat over regions up to at least 104 A 2 and is generally free of gross microstructural defects. Thus, HOPG serves well as a nearly perfect single-crystal surface for studies of the chemical properties of basal plane sp 2 carbon. In previous reports on laser activation of HOPG, it was demonstrated that electrode capacitance, electron transfer kinetics, and Raman spectrum depend on laser-induced disorder, particularly edge plane defects. The present work was undertaken to describe surface defects on HOPG at the STM level for two grades of HOPG and the laser-activated surface. Capacitance, k ~ for Fe(CN)~ 3j-4, and anthraquinone disulfonate adsorption all correlate with the presence of STM observable defects. In addition, STM of the laser-activated surface is consistent with a damage mechanism driven by thermal expansion. The results confirm the importance of edge plane defects to the electrochemical behavior of carbon electrodes.

Publisher Summary This chapter outlines the drug testing methods that are available to analyze recreational, psychiatric, cognition enhancing, or mood altering drugs. The chapter discusses the techniques currently used for the analysis of psychoactive drugs and attempts to forecast methods that are likely to find a place in drug analysis within the next few years and beyond. The chapter attempts to predict how advances in analytical science—such as miniaturization—linked with advances in electronics and increased instrumental sensitivity might develop over the coming years. The three most likely significant advances are miniaturization (enabling point-of-care analysis), high throughput screening using enhanced spectrophotometric detection of antibody binding of drugs of interest, and enhanced separation techniques for the discrimination of complex mixtures. This approach is likely to become more important if metabolomics (the study of the small molecules, or metabolites, contained in a human cell, tissue, or organ involved in primary and intermediary metabolism) is used to indicate that a psychoactive substance is used.

Researchers are advocating that a necessary condition of scholarly research is congruence between philosophical positions and research approaches. Phenomenology and postpositivism, traditionally, may appear to be situated in scientific inquiry as polar opposites and mutually exclusive paradigms. This article (a) describes the reflections of a nurse researcher and clarifies her philosophical assumptions; (b) delineates the postpositive paradigm and the interpretive paradigm, which traditionally includes phenomenology; (c) discusses phenomenology as a philosophy, an approach, and a research method; and (d) demonstrates the consistency between postpositivism and phenomenology. Nurse researchers must be aware of their philosophical assumptions and appraise the philosophical underpinnings of the methodologies, but this process should not restrict and limit their exploration of possibilities and the creativity in their efforts to address the growing challenges that await nursing science research.

This study evaluated the health effects of routine and intensified dental care and disease prevention in persons with human immunodeficiency virus (HIV). We recruited 376 HIV-infected persons ages 19 to 61 with CD4 counts between 100 and 750 into a year-long two-arm randomized controlled trial. Control group subjects (n = 185) received professional dental protective treatment and checkups at baseline, 6 months, and 1 year, plus dental care. Enhanced care patients (n = 191) received bimonthly protective treatment and twice-daily chlorhexidine mouthrinses to treat gingivitis. Active decay, gingivitis, oral pain, impact of oral health on functioning, and global functional status improved in both groups. The mean depth of periodontal pockets decreased 0.18 mm (control group) versus 0.27 mm (enhanced group) (p < 0.04), as did an erythema index (-1.22 versus -1.78, p < 0.01). No effects on acquired immune deficiency syndrome (AIDS)-related complications, symptoms, or mortality were observed. We concluded that access to dental screening, prophylaxis, and repair will significantly improve oral health, functioning, and quality of life in persons with AIDS.

Studies have been carried out on the use of octamer oligonucleotides tailed with different base analogues as primers in cycle sequencing reactions. 5-Nitroindole tails improved the performance as primers of a number of octamers. A tail length of three or four 5-nitroindole residues significantly increased the sequencing signal intensity for almost all primers. The use of incomplete libraries of tailed octamer primers for primer walking is discussed.

An audio speaker with at least two electric coils on opposite sides of at least one ferro-magnetic plate, the coils and plate forming a radial electro-magnet. A radial electro-magnet can offer many advantages in stereo loudspeakers. The coils are electrically driven in opposite directions. Multiple sets of two coils and intervening ferro-magnetic plate may be provided, adjacent sets being separated by a non-magnetic plate.

To establish the normal pattern of postoperative tracer uptake we performed 73 99mtechnetium methylene diphosphonate scans following primary Charnley hip replacements for arthrosis in 68 patients without clinical, hematological and radiographic complications. The patients were divided into 7 subgroups according to the period, 6-24 months, between surgery and scan. There were 10-12 patients in each subgroup. A high-resolution gamma camera with a large field of view was used. Ratios of uptake in each of 10 peri-prosthetic zones to normal bone were calculated. Femoral uptake was found to decrease in linear fashion from 6 to 12 months after surgery. Thereafter the uptake remained unaltered at levels nearly twice the normal ones in the greater trochanter and nearly 1.5 times in the lesser trochanter, returning to almost normal levels in other zones. Acetabular uptake remained elevated throughout.

Carbon electrodes form the basis of a variety of electroanalytical sensors, in part due to their low cost, wide potential range, and suitability for modification. A major research effort is underway in many laboratories to understand better the properties of carbon electrodes regarding electrocatalytic activity and other factors such as background current and electron transfer activity. One method of improving the performance of these electrode materials involves the application of pulses from a Nd:YAG or N2 laser, either during or prior to electrochemical use. Both electrochemical and spectroscopic probes indicate dramatic changes to the surface of the electrodes after the pulses. Raman spectroscopy of the electrode surface indicates damage to the carbon lattice, with an increase in intensity of the Raman band at 1360 cm−1. This band is active in crystallites of finite size, and indicates increased exposure of graphitic edge plane. Also, there is a dramatic increase (≥106×) in heterogeneous charge‐transf...

A beam of light reflected from a 50–400 μm diameter disk electrode was used to monitor the concentration of an electrogenerated absorber in the submicrosecond time scale. The electrode potential was established in less than 1 μs after a potential step, and charge injection further reduced this response time to less than 40 ns. Absorbance measurements agreed with theory for planar diffusion from 150 ns to 100 ms, at which point nonlinear diffusion caused a negative deviation from planar behavior. The technique was used to monitor the kinetics of the oxidation of dopamine by electrogenerated chlorpromazine cation radical. The method was used to monitor this process in the physiological pH region, where the reaction is too fast for stopped-flow techniques.

Background Extracorporeal Membrane Oxygenation (ECMO) is a technology used in treatment of patients with severe but potentially reversible respiratory failure. A multi-centre randomised controlled trial (CESAR) was funded in the UK to compare care including ECMO with conventional intensive care management. The protocol and funding for the CESAR trial included plans for economic data collection and analysis. Given the high cost of treatment, ECMO is considered an expensive technology for many funding systems. However, conventional treatment for severe respiratory failure is also one of the more costly forms of care in any health system. Methods/Design The objectives of the economic evaluation are to compare the costs of a policy of referral for ECMO with those of conventional treatment; to assess cost-effectiveness and the cost-utility at 6 months follow-up; and to assess the cost-utility over a predicted lifetime. Resources used by patients in the trial are identified. Resource use data are collected from clinical report forms and through follow up interviews with patients. Unit costs of hospital intensive care resources are based on parallel research on cost functions in UK NHS intensive care units. Other unit costs are based on published NHS tariffs. Cost effectiveness analysis uses the outcome: survival without severe disability. Cost utility analysis is based on quality adjusted life years gained based on the Euroqol EQ-5D at 6 months. Sensitivity analysis is planned to vary assumptions about transport costs and method of costing intensive care. Uncertainty will also be expressed in analysis of individual patient data. Probabilities of cost effectiveness given different funding thresholds will be estimated. Discussion In our view it is important to record our methods in detail and present them before publication of the results of the trial so that a record of detail not normally found in the final trial reports can be made available in the public domain. Trial Registrations The CESAR trial registration number is ISRCTN47279827.

Background Acinetobacter baumannii is a nonfermentative Gramnegative bacillus, which easily acquires antibiotic resistance determinants and causes life-threatening nosocomial infections [1]. Multi-drug resistant (MDR) strains are common therefore, empirical treatment choices are limited. More knowledge is needed regarding genetic diversity patterns and resistance phenotypes in a given clinical setting. Our goal is to identify the resistance genotypes of A. baumanii at Nashville General Hospital and correlate them with MDR phenotypes [1].