Petrogenesis of diachronous mixed siliciclastic-carbonate megafacies in the cool-water Oligocene Tikorangi Formation, Taranaki Basin, New Zealand

The Oligocene (Whaingaroan-Waitakian) Tikorangi Formation is a totally subsurface, lithostratigraphically complex, mixed siliciclastic-limestone-rich sequence forming an important fracture reservoir within Taranaki Basin, New Zealand. Petrographically the formation comprises a spectrum of interbedded rock types ranging from calcareous mudstone to wackestone to packstone to clean sparry grainstone. Skeletal and textural varieties within these rock types have aided in the identification of three environmentally distinctive megafacies for the Tikorangi Formation rocks-shelfal, foredeep, and basinal. Data from these megafacies have been used to detail previous conclusions on the petrogenesis and to further refine depositional paleoenvironmental models for the Tikorangi Formation in the central eastern Taranaki Basin margin.Shelfal Megafacies 1 rocks (reference well Hu Road-1A) are latest Oligocene (early Waitakian) in age and formed on or proximal to the Patea-Tongaporutu-Herangi basement high. They are characterised by coarse, skeletal-rich, pure sparry grainstone comprising shallow water, high energy taxa (bryozoans, barnacles, red algae) and admixtures of coarse well-rounded lithic sand derived from Mesozoic basement greywacke. This facies type has previously gone unrecorded in the Tikorangi Formation. Megafacies 2 is a latest Oligocene (early Waitakian) foredeep megafacies (formerly named shelfal facies) formed immediately basinward and west of the shelfal basement platform. It accumulated relatively rapidly (>20 cm/ka) from redeposition of shelfal megafacies biota that became intermixed with bathyal taxa to produce a spectrum of typically mudstone through to sparry grainstone. The resulting skeletal mix (bivalve, echinoderm, planktic and benthic foraminiferal, red algal, bryozoan, nannofossil) is unlike that in any of the age-equivalent limestone units in neighbouring onland King Country Basin. Megafacies 3 is an Oligocene (Whaingaroan-Waitakian) offshore basinal megafacies (formerly termed bathyal facies) of planktic foraminiferal-nannofossil-siliciclastic wackestone and mudstone formed away from redepositional influences. The siliciclastic input in this distal basinal setting (sedimentation rates <7 mm/ka) was probably sourced mainly from oceanic currents carrying suspended sediment from South Island provenances exposed at this time.Tikorangi Formation rocks record the Taranaki Basin’s only period of carbonate-dominated sedimentation across a full range of shelfal, foredeep, and basinal settings. Depositional controls on the three contrasting megafacies were fundamentally the interplay of an evolving and complex plate tectonic setting, including development of a carbonate foredeep, changes in relative sea level within an overall transgressive regime, and changing availability, sources, and modes of deposition of both bioclastic and siliciclastic sediments. The mixed siliciclastic-carbonate nature of the formation, and its skeletal assemblages, low-Mg calcite mineralogy, and delayed deep burial diagenetic history, are features consistent with formation in temperate-latitude cool waters

Late Miocene to early Pliocene stratigraphic record in northern Taranaki Basin: Condensed sedimentation ahead of Northern Graben extension and progradation of the modern continental margin

The middle Pliocene-Pleistocene progradation of the Giant Foresets Formation in Taranaki Basin built up the modern continental margin offshore from western North Island. The late Miocene to early Pliocene interval preceding this progradation was characterised in northern Taranaki Basin by the accumulation of hemipelagic mudstone (Manganui Formation), volcaniclastic sediments (Mohakatino Formation), and marl (Ariki Formation), all at bathyal depths. The Manganui Formation has generally featureless wireline log signatures and moderate to low amplitude seismic reflection characteristics. Mohakatino Formation is characterised by a sharp decrease in the GR log value at its base, a blocky GR log motif reflecting sandstone packets, and erratic resistivity logs. Seismic profiles show bold laterally continuous reflectors. The Ariki Formation has a distinctive barrel-shaped to blocky GR log motif. This signature is mirrored by the SP log and often by an increase in resistivity values through this interval. The Ariki Formation comprises (calcareous) marl made up of abundant planktic foraminifera, is 109 m thick in Ariki-1, and accumulated over parts of the Western Stable Platform and beneath the fill of the Northern Graben. It indicates condensed sedimentation reflecting the distance of the northern region from the contemporary continental margin to the south

Textural variations in Neogene pelagic carbonate ooze at DSDP Site 593, southern Tasman Sea, and their paleoceanographic implications

Changes in Neogene sediment texture in pelagic carbonate-rich oozes on the Challenger Plateau, southern Tasman Sea, are used to infer changes in depositional paleocurrent velocities. The most obvious record of textural change is in the mud:sand ratio. Increases in the sand content are inferred to indicate a general up-core trend towards increasing winnowing of sediments resulting from increasing flow velocity of Southern Component Intermediate Water (SCIW), the forerunner of Antarctic Intermediate Water. In particular, the intervals c. 19-14.5 Ma, c. 9.5-8 Ma, and after 5 Ma are suggested to be times of increased SCIW velocity and strong sediment winnowing. Within the mud fraction, the fine silt to coarse clay sizes from 15.6 to 2 µm make the greatest contribution to the sediments and are composed of nannofossil plates. During extreme winnowing events it is the fine silt to very coarse clay material (13-3 µm) within this range that is preferentially removed, suggesting the 10 µm cohesive silt boundary reported for siliciclastic sediments does not apply to calcitic skeletal grains. The winnowed sediment comprises coccolithophore placoliths and spheres, represented by a mode at 4-7 µm. Further support for seafloor winnowing is gained from the presence in Hole 593 of a condensed sedimentary section from c. 18 to 14 Ma where the sand content increases to c. 20% of the bulk sample. Associated with the condensed section is a 6 m thick orange unit representing sediments subjected to particularly oxygen-rich, late early to early middle Miocene SCIW. Together these are inferred to indicate increased SCIW velocity resulting in winnowed sediment associated with faster arrival of oxygen-rich surface water subducted to form SCIW. Glacial development of Antarctica has been recorded from many deep-sea sites, with extreme glacials providing the mechanism to increase watermass flow. Miocene glacial zones Mi1b-Mi6 are identified in an associated oxygen isotope record from Hole 593, and correspond with times of particularly invigorated paleocirculation, bottom winnowing, and sediment textural changes

Retinal glycoprotein enrichment by concanavalin a enabled identification of novel membrane autoantigen synaptotagmin-1 in equine recurrent uveitis.

Complete knowledge of autoantigen spectra is crucial for understanding pathomechanisms of autoimmune diseases like equine recurrent uveitis (ERU), a spontaneous model for human autoimmune uveitis. While several ERU autoantigens were identified previously, no membrane protein was found so far. As there is a great overlap between glycoproteins and membrane proteins, the aim of this study was to test whether pre-enrichment of retinal glycoproteins by ConA affinity is an effective tool to detect autoantigen candidates among membrane proteins. In 1D Western blots, the glycoprotein preparation allowed detection of IgG reactions to low abundant proteins in sera of ERU patients. Synaptotagmin-1, a Ca2+-sensing protein in synaptic vesicles, was identified as autoantigen candidate from the pre-enriched glycoprotein fraction by mass spectrometry and was validated as a highly prevalent autoantigen by enzyme-linked immunosorbent assay. Analysis of Syt1 expression in retinas of ERU cases showed a downregulation in the majority of ERU affected retinas to 24%. Results pointed to a dysregulation of retinal neurotransmitter release in ERU. Identification of synaptotagmin-1, the first cell membrane associated autoantigen in this spontaneous autoimmune disease, demonstrated that examination of tissue fractions can lead to the discovery of previously undetected novel autoantigens. Further experiments will address its role in ERU pathology

Continental-scale geographic change across zealandia during paleogene subduction initiation

Data from International Ocean Discovery Program (IODP) Expedition 371 reveal vertical movements of 1-3 km in northern Zealandia during early Cenozoic subduction initiation in the western Pacific Ocean. Lord Howe Rise rose from deep (~1 km) water to sea level and subsided back, with peak uplift at 50 Ma in the north and between 41 and 32 Ma in the south. The New Caledonia Trough subsided 2-3 km between 55 and 45 Ma. We suggest these elevation changes resulted from crust delamination and mantle flow that led to slab formation. We propose a "subduction resurrection" model in which (1) a subduction rupture event activated lithospheric-scale faults across a broad region during less than ~5 m.y., and (2) tectonic forces evolved over a further 4-8 m.y. as subducted slabs grew in size and drove plate-motion change. Such a subduction rupture event may have involved nucleation and lateral propagation of slip-weakening rupture along an interconnected set of preexisting weaknesses adjacent to density anomalies

Mid- to late Pliocene (3.3-2.6 Ma) global sea-level fluctuations recorded on a continental shelf transect, Whanganui Basin, New Zealand

We present a similar to 900 m-thick, mid- (3.3-3.0 Ma) to late Pliocene (3.0-2.6 Ma), shallow-marine, cyclical sedimentary succession from Whanganui Basin, New Zealand that identifies paleobathymetric changes, during a warmer-than-present interval of Earth history, relevant to future climate change. Our approach applies lithofacies, sequence stratigraphy and benthic foraminiferal analyses to two continuously-cored drillholes integrated with new and existing outcrop studies. We construct a depositional model of orbitally-paced, global sea-level changes on a wave-graded continental shelf. Unlike many previous studies, these shelf sediments were not eroded during sea-level lowstands and thus provide the potential to reconstruct the full amplitude of glacial-interglacial sea-level change. Paleobathymetric interpretations are underpinned by analysis of extant benthic foraminiferal census data and a statistical correlation with the distribution of modern taxa. In general, water depths derived from foraminiferal Modern Analogue Technique (MAT), are consistent with variability recorded by lithofacies. The inferred sea-level cycles co-vary with a qualitative climate record reconstructed from a census of extant pollen and spores, and a modern temperature relationship. A high -resolution age model is established using magnetostratigraphy constrained by biostratigraphy, and the dating and correlation of tephra. This integrated chronostratigraphy allows the recognition of 23 individual sedimentary cycles, that are correlated across the paleo-shelf and a possible "one-to-one" relationship is made to deep-ocean benthic oxygen isotope (delta O-18) records. In general water depth changes were paced by similar to 20 kyr duration between 3.3 and 3.0 Ma, after which cycle duration is similar to 40 kyr during the late Pliocene (3.0-2.6 Ma). This record provides a future opportunity to evaluate the amplitude and frequency of global, Pliocene glacioeustatic sea-level change, independent of the global benthic delta O-18 record. (C) 2018 Elsevier Ltd. All rights reserve

Seizure-Related Gene 6 (Sez-6) in Amacrine Cells of the Rodent Retina and the Consequence of Gene Deletion

Background: Seizure-related gene 6 (Sez-6) is expressed in neurons of the mouse brain, retina and spinal cord. In the cortex, Sez-6 plays a role in specifying dendritic branching patterns and excitatory synapse numbers during development. Methodology/Principal Findings: The distribution pattern of Sez-6 in the retina was studied using a polyclonal antibody that detects the multiple isoforms of Sez-6. Prominent immunostaining was detected in GABAergic, but not in All glycinergic, amacrine cell subpopulations of the rat and mouse retina. Amacrine cell somata displayed a distinct staining pattern with the Sez-6 antibody: a discrete, often roughly triangular-shaped bright spot positioned between the nucleus and the apical dendrite superimposed over weaker general cytoplasmic staining. Displaced amacrines in the ganglion cell layer were also positive for Sez-6 and weaker staining was occasionally observed in neurons with the morphology of alpha ganglion cells. Two distinct Sez-6 positive strata were present in the inner plexiform layer in addition to generalized punctate staining. Certain inner nuclear layer cells, including bipolar cells, stained more weakly and diffusely than amacrine cells, although some bipolar cells exhibited a perinuclear "bright spot" similar to amacrine cells. In order to assess the role of Sez-6 in the retina, we analyzed the morphology of the Sez-6 knockout mouse retina with immunohistochemical markers and compared ganglion cell dendritic arbor patterning in Sez-6 null retinae with controls. The functional importance of Sez-6 was assessed by dark-adapted paired-flash electroretinography (ERG). Conclusions: In summary, we have reported the detailed expression pattern of a novel retinal marker with broad cell specificity, useful for retinal characterization in rodent experimental models. Retinal morphology, ganglion cell dendritic branching and ERG waveforms appeared normal in the Sez-6 knockout mouse suggesting that, in spite of widespread expression of Sez-6, retinal function in the absence of Sez-6 is not affected

Patient-reported outcomes in metastatic castration-resistant prostate cancer

Many novel therapies are available for use in patients with metastatic castration-resistant prostate cancer (mCRPC), some of which convey substantial progression-free survival and overall survival benefits. Delaying disease progression and providing palliation of symptoms are primary therapeutic aims of treating patients with mCRPC; therefore, ensuring that the benefit-to-harm ratios are acceptable to patients, through systematic measurement of patient-reported outcomes (PROs) using validated tools, is vital. In this Perspectives, we appraised the published reports from clinical trials testing treatments of mCRPC over the past 5 years and found that PROs were either not being measured routinely, or if used, were often not reported adequately, thus hampering evaluation of the true effects of many of these treatments on patients' quality of life. Improvements are needed because data collected directly from patients, not just physician-collected safety data and adverse events, are crucial to inform clinical decision-making on treatment options

Management of Patients with Advanced Prostate Cancer: Report from the Advanced Prostate Cancer Consensus Conference 2021.

BACKGROUND: Innovations in treatments, imaging, and molecular characterisation in advanced prostate cancer have improved outcomes, but various areas of management still lack high-level evidence to inform clinical practice. The 2021 Advanced Prostate Cancer Consensus Conference (APCCC) addressed some of these questions to supplement guidelines that are based on level 1 evidence. OBJECTIVE: To present the voting results from APCCC 2021. DESIGN, SETTING, AND PARTICIPANTS: The experts identified three major areas of controversy related to management of advanced prostate cancer: newly diagnosed metastatic hormone-sensitive prostate cancer (mHSPC), the use of prostate-specific membrane antigen ligands in diagnostics and therapy, and molecular characterisation of tissue and blood. A panel of 86 international prostate cancer experts developed the programme and the consensus questions. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The panel voted publicly but anonymously on 107 pre-defined questions, which were developed by both voting and non-voting panel members prior to the conference following a modified Delphi process. RESULTS AND LIMITATIONS: The voting reflected the opinions of panellists and did not incorporate a standard literature review or formal meta-analysis. The answer options for the consensus questions received varying degrees of support from panellists, as reflected in this article and the detailed voting results reported in the Supplementary material. CONCLUSIONS: These voting results from a panel of experts in advanced prostate cancer can help clinicians and patients to navigate controversial areas of management for which high-level evidence is scant. However, diagnostic and treatment decisions should always be individualised according to patient characteristics, such as the extent and location of disease, prior treatment(s), comorbidities, patient preferences, and treatment recommendations, and should also incorporate current and emerging clinical evidence and logistic and economic constraints. Enrolment in clinical trials should be strongly encouraged. Importantly, APCCC 2021 once again identified salient questions that merit evaluation in specifically designed trials. PATIENT SUMMARY: The Advanced Prostate Cancer Consensus Conference is a forum for discussing current diagnosis and treatment options for patients with advanced prostate cancer. An expert panel votes on predefined questions focused on the most clinically relevant areas for treatment of advanced prostate cancer for which there are gaps in knowledge. The voting results provide a practical guide to help clinicians in discussing treatment options with patients as part of shared decision-making

Management of Patients with Advanced Prostate Cancer: Report of the Advanced Prostate Cancer Consensus Conference 2019.

Background Innovations in treatments, imaging, and molecular characterisation in advanced prostate cancer have improved outcomes, but there are still many aspects of management that lack high-level evidence to inform clinical practice. The Advanced Prostate Cancer Consensus Conference (APCCC) 2019 addressed some of these topics to supplement guidelines that are based on level 1 evidence.Objective To present the results from the APCCC 2019.Design, setting, and participants Similar to prior conferences, experts identified 10 important areas of controversy regarding the management of advanced prostate cancer: locally advanced disease, biochemical recurrence after local therapy, treating the primary tumour in the metastatic setting, metastatic hormone-sensitive/naïve prostate cancer, nonmetastatic castration-resistant prostate cancer, metastatic castration-resistant prostate cancer, bone health and bone metastases, molecular characterisation of tissue and blood, inter- and intrapatient heterogeneity, and adverse effects of hormonal therapy and their management. A panel of 72 international prostate cancer experts developed the programme and the consensus questions.Outcome measurements and statistical analysis The panel voted publicly but anonymously on 123 predefined questions, which were developed by both voting and nonvoting panel members prior to the conference following a modified Delphi process.Results and limitations Panellists voted based on their opinions rather than a standard literature review or formal meta-analysis. The answer options for the consensus questions had varying degrees of support by the panel, as reflected in this article and the detailed voting results reported in the Supplementary material.Conclusions These voting results from a panel of prostate cancer experts can help clinicians and patients navigate controversial areas of advanced prostate management for which high-level evidence is sparse. However, diagnostic and treatment decisions should always be individualised based on patient-specific factors, such as disease extent and location, prior lines of therapy, comorbidities, and treatment preferences, together with current and emerging clinical evidence and logistic and economic constraints. Clinical trial enrolment for men with advanced prostate cancer should be strongly encouraged. Importantly, APCCC 2019 once again identified important questions that merit assessment in specifically designed trials.Patient summary The Advanced Prostate Cancer Consensus Conference provides a forum to discuss and debate current diagnostic and treatment options for patients with advanced prostate cancer. The conference, which has been held three times since 2015, aims to share the knowledge of world experts in prostate cancer management with health care providers worldwide. At the end of the conference, an expert panel discusses and votes on predefined consensus questions that target the most clinically relevant areas of advanced prostate cancer treatment. The results of the voting provide a practical guide to help clinicians discuss therapeutic options with patients as part of shared and multidisciplinary decision making