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The demand for high-resolution imaging, and high sample throughputs in LA-ICP-MS experiments has led to developing rapid-response ablation cells with low dispersion. These cells can achieve short transient signals called single pulse responses (SPRs), whose width is in the single-digit millisecond range at 1% of the maximum. However, coupled with ICP-Q-MS, recording those short signals poses a problem due to the sequential measurement of selected m/z ratios. If more than one m/z ratio is targeted, the time resolution of quadrupole detection systems is insufficient for accurately determining short SPRs. This work focuses on utilizing rapid response ablation cells for the analysis of multiple elements with quadrupole-based detection systems in the SPR mode. To achieve this, an ArF-excimer laser equipped with a rapid-response ablation chamber is coupled to an ICP-MS with a short settling time of 0.2 ms and below. The two naturally occurring Ag-isotopes were analyzed in the NIST SRM 612 to optimize the dwell times for ideal data acquisition. The data shows that the ratio of the dwell time and the settling time, plays a crucial role. With the optimized parameters, the natural ratio of 107Ag and 109Ag within a 10 ms FW0.01M transient signal could be determined. This concept of LA-ICP-MS was then applied for depth profiling analysis of Al-doped SiC, a wide bandgap semiconductor. This procedure acquired depth profiles on 30 different sample locations in approximately 2 minutes with an exceptional depth resolution of 55 nm. [ABSTRACT FROM AUTHOR]

The treatment of metastatic melanoma has been revolutionised by immunotherapy, yet a significant number of patients do not respond, and many experience autoimmune adverse events. Associations have been reported between patient outcome and monocyte subsets, whereas vitamin C (ascorbate) has been shown to mediate changes in cancer-stimulated monocytes in vitro. We therefore investigated the relationship of ascorbate with monocyte subsets and epigenetic modifications in patients with metastatic melanoma receiving immunotherapy. Patients receiving immunotherapy were compared to other cancer cohorts and age-matched healthy controls. Ascorbate levels in plasma and peripheral blood-derived mononuclear cells (PBMCs), monocyte subtype and epigenetic markers were measured, and adverse events, tumour response and survival were recorded. A quarter of the immunotherapy cohort had hypovitaminosis C, with plasma and PBMC ascorbate levels significantly lower than those from other cancer patients or healthy controls. PBMCs from the immunotherapy cohort contained similar frequencies of non-classical and classical monocytes. DNA methylation markers and intracellular ascorbate concentration were correlated with monocyte subset frequency in healthy controls, but correlation was lost in immunotherapy patients. No associations between ascorbate status and immune-related adverse events or tumour response or overall survival were apparent. [ABSTRACT FROM AUTHOR]

To constrain global warming, we must strongly curtail greenhouse gas emissions and capture excess atmospheric carbon dioxide.sup.1,2. Regrowing natural forests is a prominent strategy for capturing additional carbon.sup.3, but accurate assessments of its potential are limited by uncertainty and variability in carbon accumulation rates.sup.2,3. To assess why and where rates differ, here we compile 13,112 georeferenced measurements of carbon accumulation. Climatic factors explain variation in rates better than land-use history, so we combine the field measurements with 66 environmental covariate layers to create a global, one-kilometre-resolution map of potential aboveground carbon accumulation rates for the first 30 years of natural forest regrowth. This map shows over 100-fold variation in rates across the globe, and indicates that default rates from the Intergovernmental Panel on Climate Change (IPCC).sup.4,5 may underestimate aboveground carbon accumulation rates by 32 per cent on average and do not capture eight-fold variation within ecozones. Conversely, we conclude that maximum climate mitigation potential from natural forest regrowth is 11 per cent lower than previously reported.sup.3 owing to the use of overly high rates for the location of potential new forest. Although our data compilation includes more studies and sites than previous efforts, our results depend on data availability, which is concentrated in ten countries, and data quality, which varies across studies. However, the plots cover most of the environmental conditions across the areas for which we predicted carbon accumulation rates (except for northern Africa and northeast Asia). We therefore provide a robust and globally consistent tool for assessing natural forest regrowth as a climate mitigation strategy. A one-kilometre-resolution map of aboveground carbon accumulation rates of forest regrowth shows 100-fold variation across the globe, with rates 32% higher on average than IPCC estimates., Author(s): Susan C. Cook-Patton [sup.1] [sup.2] , Sara M. Leavitt [sup.1] , David Gibbs [sup.3] , Nancy L. Harris [sup.3] , Kristine Lister [sup.3] , Kristina J. Anderson-Teixeira [sup.4] [sup.5] [...]

Background It is unclear whether genetic variants affecting vitamin D metabolism are associated with melanoma prognosis. Two functional missense variants in the vitamin D–binding protein gene (GC), rs7041 and rs4588, determine 3 common haplotypes, Gc1s, Gc1f, and Gc2, of which Gc1f may be associated with decreased all-cause death among melanoma patients based on results of a prior study, but the association of Gc1f with melanoma-specific death is unclear. Methods We investigated the association of the Gc1s, Gc1f, and Gc2 haplotypes with melanoma-specific and all-cause death among 4490 individuals with incident, invasive primary melanoma in 2 population-based studies using multivariable Cox-proportional hazards regression. Results In the pooled analysis of both datasets, the patients with the Gc1f haplotype had a 37% lower risk of melanoma-specific death than the patients without Gc1f (hazard ratio [HR] = 0.63, 95% confidence interval [CI] = 0.47 to 0.83, P  =  .001), with adjustments for age, sex, study center, first- or higher-order primary melanoma, tumor site, pigmentary phenotypes, and Breslow thickness. Associations were similar in both studies. In pooled analyses stratified by Breslow thickness, the corresponding melanoma-specific death HRs for those patients with the Gc1f haplotype compared with those without Gc1f were 0.89 (95% CI = 0.63 to 1.27) among participants with tumor Breslow thickness equal to or less than 2.0 mm and 0.40 (95% CI = 0.25 to 0.63) among participants with tumor Breslow thickness greater than 2.0 mm (P interaction   =  .003). Conclusions Our findings suggest that individuals with the GC haplotype Gc1f may have a lower risk of dying from melanoma—specifically from thicker, higher-risk melanoma—than individuals without this Gc1f haplotype. [ABSTRACT FROM AUTHOR]

The efficacy of PD-1 monoclonals such as pembrolizumab can be modulated by the signals delivered via their Fc region. Tumour/inflammation associated proteases can generate F(ab')2 fragments of therapeutic monoclonals, and subsequent recognition of F(ab')2 epitopes by circulating anti-hinge antibodies (AHA) can then, potentially, link F(ab')2 binding to the target antigen with novel Fc signalling. Although elevated in inflammatory diseases, AHA levels in cancer patients have not been investigated and functional studies utilising the full repertoire of AHA present in sera have been limited. AHA levels in pembrolizumab treated melanoma patients (n = 23) were therefore compared to those of normal donors and adalimumab treated patients. A subset of melanoma patients and the majority of adalimumab patients had elevated levels of AHA reactive with F(ab')2 fragments of IgG4 anti-PD-1 monoclonals (nivolumab, pembrolizumab) and IgG1 therapeutic monoclonals (rituximab, adalimumab). Survival analysis was restricted by the small patient numbers but those melanoma patients with the highest levels (>75% percentile, n = 5) of pembrolizumab-F(ab')2 reactive AHA had significantly better overall survival post pembrolizumab treatment (p = 0.039). In vitro functional studies demonstrated that the presence of AHA+ sera restored the neutrophil activating capacity of pembrolizumab to its F(ab')2 fragment. Neither pembrolizumab nor its F(ab')2 fragments can induce NK cell or complement dependent cytotoxicity (CDC). However, AHA+ sera in combination with pembrolizumab-F(ab')2 provided Fc regions that could activate NK cells. The ability of AHA+ sera to restore CDC activity was more restricted and observed using only one pembrolizumab and one adalimumab patient serum in combination with rituximab- F(ab')2. This study reports the presence of elevated AHA levels in pembrolizumab treated melanoma patients and highlight the potential for AHA to provide additional Fc signaling. The issue of whether tumour associated proteolysis of PD-1 mAbs and subsequent AHA recognition impacts on treatment efficacy requires further study. [ABSTRACT FROM AUTHOR]

Background: There are several approaches such as the Bankart repair, Latarjet, and Remplissage to treat recurrent glenohumeral instability. Indications: We chose to augment an arthroscopic Bankart repair with a Remplissage in this 26-year-old patient given the presence of a Hill-Sachs lesion, history of recurrent shoulder dislocations, and young age of the patient. Technique Description: We established four portals using previously well-documented techniques. The Hill-Sachs lesion was evaluated using the anterosuperior portal. Two anchors were placed, one on both the superior and inferior aspects of the Hill-Sachs lesion. The sutures were shuttled through the knotless anchor mechanism and tensioned after confirming the cannula was through the deltoid. Then, we completed the Remplissage by repairing the infraspinatus tendon and capsule into the posterior humeral head. Results: The Remplissage procedure is very successful at reducing recurrent instability in young, active patients. Previous studies have reported very low rates, even 0% recurrent instability, after surgery with 80% to 90% of patients returning to sports. Studies have also documented excellent patient-reported outcomes at short- to mid-term follow-up. Complication rates are historically lower when the Remplissage is done with an arthroscopic Bankart repair than the Bankart repair alone. Discussion/Conclusion: The Remplissage procedure is a safe, effective option at reducing future instances of shoulder dislocations in conjunction with Bankart repairs. Patients can expect to return to their active lifestyles, with many patients achieving the same level of activity as before the initial shoulder dislocation. Patient Consent Disclosure Statement: The author(s) attests that consent has been obtained from any patient(s) appearing in this publication. If the individual may be identifiable, the author(s) has included a statement of release or other written form of approval from the patient(s) with this submission for publication. [ABSTRACT FROM AUTHOR]