Assessing Stratigraphic Controls on the Secondary Detrital Footprint from Buried Mineralization and Alteration at the Highland Valley Copper Mine, British Columbia

Mineral exploration is progressively shifting to deeper targets, including those buried under thick unconsolidated sediments. It is thus becoming increasingly important to understand the sedimentary successions of the shallow subsurface (0-200m) in order to enhance exploration strategies to locate and characterize buried targets. One strategy is to investigate the sedimentary sequence overlying known mineralized and altered zones. As such, this study aims to characterize stratified unconsolidated sediments overlying mineralized as well as altered zones at the Highland Valley porphyry copper system (HVC), in south-central British Columbia, and investigate their effects on dispersion patterns of indicator minerals and geochemical pathfinders. Stratigraphic logging and sedimentary facies analysis of ten drillcores have produced a new stratigraphic framework of the unconsolidated sediment cover and a refined depositional environment interpretation. Four geological cross-sections and an interpreted seismic profile improve our understanding of the stratigraphic architecture of the valley fill sediments in the vicinity of the Highland Valley Pit, as well as across the J.A. target, located four km to the east. Two new, previously unreported units are described from this study: a deeper, older till unit as well as a deglacial sequence overlying the older till unit. This study also reveals important lateral stratigraphic and sedimentary facies changes over relatively short distances. Two major ice advance and retreat cycles, the 1st one being older than 50 ka, and additional minor oscillations of ice margins during the last deglaciation of the area, are recognized in the stratigraphic record. Petrophysical (density, porosity, magnetic susceptibility, resistivity, and chargeability) and sedimentological (grain size) property measurements are presented for the major cover units, which can help better resolve the geophysical footprint of buried targets. Stratigraphic units interpreted to have formed by meltwater related processes and deposited in ice-marginal or proglacial settings generally have a higher proportion of locally-derived lithologies relative to other units, while tills have a more dominantly distal signature. Several porphyry copper indicator minerals, such as pyrite, chalcopyrite, and jarosite, are found in each of the Quaternary sediment cover sub-units analyzed. The strongest overall footprint of mineralization is found in two deep, poorly-sorted outwash and two deeper subglacial tills. They contain variably abundant indicator minerals (e.g. pyrite, chalcopyrite, Mn-epidote, chromite) and elements (Cu, Mo, W, As) that are indicative of porphyry copper mineralization. The source of most of these indicators is predominantly the Guichon Creek batholith that hosts the mineralization, but some indicators may be derived from distal volcanic rocks and volcanogenic sediments outside of the batholith. Coarse grain size and felsic lithology distinguished Guichon Creek batholith material from the others. Hyperspectral techniques were applied to determine the abundance of prehnite (distal alteration footprint) and kaolinite (proximal alteration footprint) in large (>2 mm) clasts. Overall, results are consistent with the abundance of clasts sourced from Guichon Creek batholith (lower prehnite content and higher kaolinite content = higher GCB clast abundance). This finding suggests the technique may be used to get insights into the proximity of the source of clasts relative to buried HVC-type mineralization. Subsurface till units also appear to have higher abundances of several indicator minerals (e.g. pyrite, chalcopyrite, jarosite) and geochemical pathfinders of mineralization (e.g. Cu, Mo, W, As) and alteration (e.g. Mg, Te, Bi) compared to previously published surficial till data. Oxidation of the surficial till and water-mineral interactions in the deeper (water-saturated) tills may explain some of the observed differences (esp. for mobile elements); however, re-entrainment of pre-existing sediments is another important mechanism to consider. The strongest footprint signal occurs in the deepest tills. Mineralized and altered bedrock thus appears to have been more accessible to glacial erosion during the older glacial phases due to less preserved sedimentary cover in depressions. Indirect sources (sediment re-entrainment) may have contributed to the footprint signal in the surficial till, perhaps more than shallow mineralized sources in some places. Overall, this study provides several refinements to the stratigraphic framework of the sedimentary cover at HVC, as well as new insights into the occurrence and abundance of HVC-related indicator minerals and pathfinders in these units. One important implication of this study is that dilution up the stratigraphy is clear but limited at HVC; however, it could be greater in other prospective thick drift areas; stronger dilution in surficial units is possible, which could mask a clear subsurface footprint and buried sources of importance

Protective Effects of PACAP in a Rat Model of Diabetic Neuropathy

Pituitary adenylate cyclase-activating peptide (PACAP) is a neuropeptide with a widespread occurrence and diverse effects. PACAP has well-documented neuro- and cytoprotective effects, proven in numerous studies. Among others, PACAP is protective in models of diabetes-associated diseases, such as diabetic nephropathy and retinopathy. As the neuropeptide has strong neurotrophic and neuroprotective actions, we aimed at investigating the effects of PACAP in a rat model of streptozotocin-induced diabetic neuropathy, another common complication of diabetes. Rats were treated with PACAP1-38 every second day for 8 weeks starting simultaneously with the streptozotocin injection. Nerve fiber morphology was examined with electron microscopy, chronic neuronal activation in pain processing centers was studied with FosB immunohistochemistry, and functionality was assessed by determining the mechanical nociceptive threshold. PACAP treatment did not alter body weight or blood glucose levels during the 8-week observation period. However, PACAP attenuated the mechanical hyperalgesia, compared to vehicle-treated diabetic animals, and it markedly reduced the morphological signs characteristic for neuropathy: axon–myelin separation, mitochondrial fission, unmyelinated fiber atrophy, and basement membrane thickening of endoneurial vessels. Furthermore, PACAP attenuated the increase in FosB immunoreactivity in the dorsal spinal horn and periaqueductal grey matter. Our results show that PACAP is a promising therapeutic agent in diabetes-associated complications, including diabetic neuropathy

Iterative reconstruction methods and the resolution principle for fast-ion loss detector measurements

Fast-ion loss detectors (FILDs) are crucial for analyzing fast-ion dynamics in magnetically confined fusion plasmas. A core challenge is to derive an accurate ion velocity distribution, requiring treatment of thousands of remapped camera frames for a full discharge. The ill-posed nature of this task necessitates regularization with a well-chosen regularization parameter and computationally efficient methods. In this work, we introduce the ‘resolution principle,’ a novel criterion for selecting the optimal regularization parameter, providing a distinction between genuine features and artefacts smaller than the diagnostic resolution in the reconstruction, thereby preventing misinterpretations. This principle, coupled with three iterative reconstruction techniques—Kaczmarz’s method, coordinate descent, and Cimmino’s method—demonstrates enhanced reconstruction capabilities compared to conventional methods like Tikhonov regularization. Utilizing these techniques allows rapid processing of measurements from full discharges, removing the computational bottleneck and facilitating between-discharge reconstructions. By reconstructing 6000 camera frames from an ELMy H-mode discharge at ASDEX Upgrade, we capture the temporal evolution of gyroradii and pitch angles, unveiling a direct correlation between pitch-angle behavior and changes in the toroidal magnetic field for a specific subset of lost ions accelerated by edge-localized modes (ELMs) to energies approximately twice that of the injection energy

A new FILDSIM model for improved velocity-space sensitivity modelling and reconstructions

We present a new version of the FILDSIM code (Galdon-Quíroga et al 2018 Plasma Phys. Control. Fusion 60 105005), which significantly refines the modelling of the fast-ion loss detector (FILD) signal. We demonstrate that the FILD weight functions computed using this new version of FILDSIM are more accurate relative to synthetic benchmarks than those computed using the previous version. Thus, the new version enables higher-quality velocity-space sensitivity modelling and reconstructions. We validate the improvements on experimental data from discharge #75620 at TCV. Additionally, we present a novel approach for characterizing FILDs through a gross FILD measurement and a gross weight function based on the calculations from the new version of FILDSIM. We use them to characterize the TCV FILD.</p

Phase II study of oral JAK1/JAK2 inhibitor ruxolitinib in advanced relapsed/refractory Hodgkin lymphoma

JAK2 constitutive activation/overexpression is common in classical Hodgkin lymphoma, and several cytokines stimulate Hodgkin lymphoma cells by recognizing JAK1-/JAK2-bound receptors. JAK blockade may thus be therapeutically beneficial in HL. This Phase II study assessed the safety and efficacy of ruxolitinib, an oral JAK1/2 inhibitor, in relapsed/refractory Hodgkin lymphoma patients. The primary objective was overall response rate according to IHP 2007 criteria. Thirty-three advanced patients (median prior lines: 5; refractory: 82%) were included; nine (27.3%) received at least 6 cycles of ruxolitinib and six (18.2%) > 6 cycles therapy. The overall response rate after 6 cycles was 3/32 (9.4%) patients, all partial responders, with transient stable disease in 11/32. Best overall response rate was 6/32 (18.8%). Rapid alleviation of B-symptoms was commonly noted. Median response duration was 7.7 months, median progression-free survival 3.5 months (95%CI: 1.9-4.6), and median overall survival 27.1 months (95%CI: 14.4-27.1). Forty adverse events were reported in 14/33 patients (42.4%); one led to treatment discontinuation; 87.5% recovered without sequelae. Twenty-five were of > Grade3. The latter consisted mostly of anemia (n=11) all considered related to ruxolitinib. Other main causes of > Grade3 adverse events included lymphopenia and infections. Of note, there was no Grade4 neutropenia or thrombocytopenia observed. Ruxolitinib shows signs of activity, though short-lived, beyond simple anti-inflammation. Its limited toxicity suggests the potential of being combined with other therapeutic modalities. ClinicalTrials.gov: NCT01877005.status: accepte

"Shoho yonhyakunijunana" giketsuken no koshi ni kansuru goi no koryoku (Tokyo kosai Heisei juninen gogatsu sanjunichi hanketsu)

JAK2 constitutive activation/overexpression is common in classical Hodgkin lymphoma, and several cytokines stimulate Hodgkin lymphoma cells by recognizing JAK1-/JAK2-bound receptors. JAK blockade may thus be therapeutically beneficial in HL. This Phase II study assessed the safety and efficacy of ruxolitinib, an oral JAK1/2 inhibitor, in relapsed/refractory Hodgkin lymphoma patients. The primary objective was overall response rate according to IHP 2007 criteria. Thirty-three advanced patients (median prior lines: 5; refractory: 82%) were included; nine (27.3%) received at least 6 cycles of ruxolitinib and six (18.2%) > 6 cycles therapy. The overall response rate after 6 cycles was 3/32 (9.4%) patients, all partial responders, with transient stable disease in 11/32. Best overall response rate was 6/32 (18.8%). Rapid alleviation of B-symptoms was commonly noted. Median response duration was 7.7 months, median progression-free survival 3.5 months (95%CI: 1.9-4.6), and median overall survival 27.1 months (95%CI: 14.4-27.1). Forty adverse events were reported in 14/33 patients (42.4%); one led to treatment discontinuation; 87.5% recovered without sequelae. Twenty-five were of > Grade3. The latter consisted mostly of anemia (n=11) all considered related to ruxolitinib. Other main causes of > Grade3 adverse events included lymphopenia and infections. Of note, there was no Grade4 neutropenia or thrombocytopenia observed. Ruxolitinib shows signs of activity, though short-lived, beyond simple anti-inflammation. Its limited toxicity suggests the potential of being combined with other therapeutic modalities. ClinicalTrials.gov: NCT01877005

Long-term survival of patients with CLL after allogeneic transplantation: A report from the European Society for Blood and Marrow Transplantation

Even with the availability of targeted drugs, allogeneic hematopoietic cell transplantation (allo-HCT) is the only therapy with curative potential for patients with CLL. Cure can be assessed by comparing long-term survival of patients to the matched general population. Using data from 2589 patients who received allo-HCT between 2000 and 2010, we used landmark analyses and methods from relative survival analysis to calculate excess mortality compared with an age-, sex- and calendar year-matched general population. Estimated event-free survival, overall survival and non-relapse mortality (NRM) 10 years after allo-HCT were 28% (95% confidence interval (CI), 25-31), 35% (95% CI, 32-38) and 40% (95% CI, 37-42), respectively. Patients who passed the 5-year landmark event-free survival (N=394) had a 79% probability (95% CI, 73-85) of surviving the subsequent 5 years without an event. Relapse and NRM contributed equally to treatment failure. Five-year mortality for 45- and 65-year-old reference patients who were event-free at the 5-year landmark was 8% and 47% compared with 3% and 14% in the matched general population, respectively. The prospect of long-term disease-free survival remains an argument to consider allo-HCT for young patients with high-risk CLL, and programs to understand and prevent late causes of failure for long-term survivors are warranted, especially for older patients