Clinicians' Understanding of Preferences and Values of People with Hematological Malignancies at the End of Life: Concurrent Surveys

Background: People with hematological malignancies can deteriorate rapidly to a terminal event and have variable levels of engagement when transitioning to palliative and end-of-life care. Objectives: To describe end-of-life care values and preferences of people with hematological malignancies and explore whether these align with hematology clinicians' perceptions. Design: Two matched anonymous quantitative cross-sectional surveys explored: (1) patients' values and preferences around manner and timing of discussions regarding life expectancy and prognosis, involvement in decision making, and concurrent integration of palliative care with active treatment; and (2) clinicians' perceptions of their patients' values and preferences in relation to prognostic information. Settings/Participants: Concurrent online national surveys of people with hematological malignancies known to the Leukemia Foundation of Australia, and clinicians in Australia with membership to the Hematology Society of Australia and New Zealand. Results: Five hundred nine (38% response rate) patients (median age 64 [min 20, max 89, interquartile range 56-70]) and 272 clinicians (21% response rate) responded to the survey. If their health was deteriorating, most patients wanted honest prognostic and life expectancy information (87%); welcomed involvement in decision making (94%); felt they would be comfortable talking to the treating team about the possibility of death (86%); and would be comfortable seeing someone from a specialist palliative care team (74%). Clinicians generally underestimated most of these responses. Conclusion: Although our findings indicate that most people believe they would be comfortable discussing prognosis, life expectancy, and wishes at the end of life, clinicians were largely unaware of their preferences. This highlights the need to embed values clarification in routine care for each patient and family.</p

Lidar Validation Measurements at the NOAA Mauna Loa Observatory NDACC Station

NASA's Goddard Space Flight Center (GSFC) transported two lidar instruments to the NOAA facility at the Mauna Loa Observatory (MLO) on the Big Island of Hawaii, to participate in an official, extended validation campaign. This site is situated 11,141 ft. above sea level on the side of the mountain. The observatory has been making atmospheric measurements regularly since the 1950's, and has hosted the GSFC Stratospheric Ozone (STROZ) Lidar and the GSFC Aerosol and Temperature (AT) Lidar on several occasions, most recently between November, 2012 and November, 2015. The purpose of this extended deployment was to participate in Network for the Detection of Atmospheric Composition Change (NDACC) Validation campaigns with the JPL Stratospheric Ozone Lidar and the NOAA Temperature, Aerosol and Water Vapor instruments as part of the routine NDACC Validation Protocol

Chemometric perspectives on plankton community responses to natural iron fertilisation over and downstream of the Kerguelen Plateau in the Southern Ocean

International audienceWe examined phytoplankton community responses to natural iron fertilisation at 32 sites over and downstream from the Kerguelen Plateau in the Southern Ocean during the austral spring bloom in October–November 2011. The community structure was estimated from chemical and isotopic measurements (particulate organic carbon – POC; 13C-POC; particulate nitrogen – PN; 15N-PN; and biogenic silica – BSi) on size-fractionated samples from surface waters (300, 210, 50, 20, 5, and 1 μm fractions). Higher values of 13C-POC (vs. co-located 13C values for dissolved inorganic carbon – DIC) were taken as indicative of faster growth rates and higher values of 15N-PN (vs. co-located 15N-NO3 source values) as indicative of greater nitrate use (rather than ammonium use, i.e. higher f ratios).Community responses varied in relation to both regional circulation and the advance of the bloom. Iron-fertilised waters over the plateau developed dominance by very large diatoms (50–210 μm) with high BSi / POC ratios, high growth rates, and significant ammonium recycling (lower f ratios) as biomass built up. In contrast, downstream polar frontal waters with a similar or higher iron supply were dominated by smaller diatoms (20–50 μm) and exhibited greater ammonium recycling. Stations in a deep-water bathymetrically trapped recirculation south of the polar front with lower iron levels showed the large-cell dominance observed on the plateau but much less biomass. Comparison of these communities to surface water nitrate (and silicate) depletions as a proxy for export shows that the low-biomass recirculation feature had exported similar amounts of nitrogen to the high-biomass blooms over the plateau and north of the polar front. This suggests that early spring trophodynamic and export responses differed between regions with persistent low levels vs. intermittent high levels of iron fertilisation

Outcomes of MYC-associated lymphomas after R-CHOP with and without consolidative autologous stem cell transplant: subset analysis of randomized trial intergroup SWOG S9704

Double hit lymphoma (DHL) and double protein-expressing (MYC and BCL2) lymphomas (DPL) fare poorly with R-CHOP; consolidative autologous stem cell transplant (ASCT) may improve outcomes. S9704, a phase III randomized study of CHOP +/−R with or without ASCT allows evaluation of intensive consolidation. Immunohistochemical analysis identified 27 of 198 patients (13.6%) with MYC IHC overexpression and 20 (74%) harboring concurrent BCL2 overexpression. Four had DHL and 16 had DPL only. With median follow-up 127 months, there is a trend favoring outcomes after consolidative ASCT in DPL and MYC protein overexpressing patients, whereas all DHL patients have died irrespective of ASCT

Investigating the basis of substrate recognition in the pC221 relaxosome

The nicking of the origin of transfer (oriT) is an essential initial step in the conjugative mobilization of plasmid DNA. In the case of staphylococcal plasmid pC221, nicking by the plasmid-specific MobA relaxase is facilitated by the DNA-binding accessory protein MobC; however, the role of MobC in this process is currently unknown. In this study, the site of MobC binding was determined by DNase I footprinting. MobC interacts with oriT DNA at two directly repeated 9 bp sequences, mcb1 and mcb2, upstream of the oriT nic site, and additionally at a third, degenerate repeat within the mobC gene, mcb3. The binding activity of the conserved sequences was confirmed indirectly by competitive electrophoretic mobility shift assays and directly by Surface Plasmon Resonance studies. Mutation at mcb2 abolished detectable nicking activity, suggesting that binding of this site by MobC is a prerequisite for nicking by MobA. Sequential site-directed mutagenesis of each binding site in pC221 has demonstrated that all three are required for mobilization. The MobA relaxase, while unable to bind to oriT DNA alone, was found to associate with a MobC–oriT complex and alter the MobC binding profile in a region between mcb2 and the nic site. Mutagenesis of oriT in this region defines a 7 bp sequence, sra, which was essential for nicking by MobA. Exchange of four divergent bases between the sra of pC221 and the related plasmid pC223 was sufficient to swap their substrate identity in a MobA-specific nicking assay. Based on these observations we propose a model of layered specificity in the assembly of pC221-family relaxosomes, whereby a common MobC:mcb complex presents the oriT substrate, which is then nicked only by the cognate MobA

Iron, silicate, and light co-limitation of three Southern Ocean diatom species

The effect of combined iron, silicate, and light co-limitation was investigated in the three diatom species Actinocyclus sp. Ehrenberg, Chaetoceros dichaeta Ehrenberg, and Chaetoceros debilis Cleve, isolated from the Southern Ocean (SO). Growth of all species was co-limited by iron and silicate, reflected in a significant increase in the number of cell divisions compared to the control. Lowest relative Si uptake and drastic frustule malformation was found under iron and silicate co-limitation in C. dichaeta, while Si limitation in general caused cell elongation in both Chaetoceros species. Higher light intensities similar to SO surface conditions showed a negative impact on growth of C. dichaeta and Actinocyclus sp. and no effect on C. debilis. This is in contrast to the assumed light limitation of SO diatoms due to deep wind driven mixing. Our results suggest that growth and species composition of Southern Ocean diatoms is influenced by a sensitive interaction of the abiotic factors, iron, silicate, and light

Current Perspectives on Tooth Implantation, Attachment, and Replacement in Amniota

Teeth and dentitions contain many morphological characters which give them a particularly important weight in comparative anatomy, systematics, physiology and ecology. As teeth are organs that contain the hardest mineralized tissues vertebrates can produce, their fossil remains are abundant and the study of their anatomy in fossil specimens is of major importance in evolutionary biology. Comparative anatomy has long favored studies of dental characters rather than features associated with tooth attachment and implantation. Here we review a large part of the historical and modern work on the attachment, implantation and replacement of teeth in Amniota. We propose synthetic definitions or redefinitions of most commonly used terms, some of which have led to confusion and conflation of terminology. In particular, there has long been much conflation between dental implantation that strictly concerns the geometrical aspects of the tooth-bone interface, and the nature of the dental attachment, which mostly concerns the histological features occurring at this interface. A second aim of this work was to evaluate the diversity of tooth attachment, implantation and replacement in extant and extinct amniotes in order to derive hypothetical evolutionary trends in these different dental traits over time. Continuous dental replacement prevails within amniotes, replacement being drastically modified only in Mammalia and when dental implantation is acrodont. By comparison, dental implantation frequently and rapidly changes at various taxonomic scales and is often homoplastic. This contrasts with the conservatism in the identity of the tooth attachment tissues (cementum, periodontal ligament, and alveolar bone), which were already present in the earliest known amniotes. Because the study of dental attachment requires invasive histological investigations, this trait is least documented and therefore its evolutionary history is currently poorly understood. Finally, it is essential to go on collecting data from all groups of amniotes in order to better understand and consequently better define dental characters

RB but not R-HCVAD is a feasible induction regimen prior to auto-HCT in frontline MCL: results of SWOG Study S1106

Aggressive induction chemotherapy followed by autologous haematopoietic stem cell transplant (auto-HCT) is effective for younger patients with mantle cell lymphoma (MCL). However, the optimal induction regimen is widely debated. The Southwesterm Oncology Group S1106 trial was designed to assess rituximab plushyperCVAD/MTX/ARAC (hyperfractionated cyclophosphamide, vincristine, doxorubicin and dexamethasone, alternating with high dose cytarabine and methotrexate) (RH) versus rituximab plus bendamustine (RB) in a randomized phase II trial to select a pre-transplant induction regimen for future development. Patients had previously untreated stage III, IV, or bulky stage II MCL and received either 4 cycles of RH or 6 cycles of RB, followed by auto-HCT. Fifty-three of a planned 160 patients were accrued; an unacceptably high mobilization failure rate (29%) on the RH arm prompted premature study closure. The estimated 2-year progression-free survival (PFS) was 81% vs. 82% and overall survival (OS) was 87% vs. 88% for RB and RH, respectively. RH is not an ideal platform for future multi-centre transplant trials in MCL. RB achieved a 2-year PFS of 81% and a 78% MRD negative rate. Premature closure of the study limited the sample size and the precision of PFS estimates and MRD rates. However, RB can achieve a deep remission and could be a platform for future trials in MCL

RB but not R‐HCVAD is a feasible induction regimen prior to auto‐HCT in frontline MCL: results of SWOG Study S1106

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/136294/1/bjh14480_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/136294/2/bjh14480.pd