Enhanced Widefield Quantum Sensing with Nitrogen-Vacancy Ensembles Using Diamond Nanopillar Arrays.

Surface micro- and nano-patterning techniques are often employed to enhance the optical interface to single photoluminescent emitters in diamond, but the utility of such surface structuring in applications requiring ensembles of emitters is still open to investigation. Here, we demonstrate scalable and fault-tolerant fabrication of closely packed arrays of fluorescent diamond nanopillars, each hosting its own dense, uniformly bright ensemble of near-surface nitrogen-vacancy centers. We explore the optimal sizes for these structures and realize enhanced spin and photoluminescence properties resulting in a 4.5 times increase in optically detected magnetic resonance sensitivity when compared to unpatterned surfaces. Utilizing the increased measurement sensitivity, we image the mechanical stress tensor in each diamond pillar across the arrays and show that the fabrication process has a negligible impact on in-built stress compared to the unpatterned surface. Our results represent a valuable pathway toward future multimodal and vector-resolved imaging studies, for instance in biological contexts.

Serial transplantation of mismatched donor hematopoietic cells between HLA-identical sibling pairs with congenital immunodeficiency: in vivo tolerance permits rapid immune reconstitution following T-replete transplantation without GVHD in the secondary recipient.

We report serial transplantation procedures in 2 sets of brothers with X-linked primary immunodeficiency. The first boy in each family received a T-cell-depleted transplant from a mismatched donor. The recipients then acted as donors for T-replete transplantation of the "tolerized" graft into their HLA-identical brothers with the same disorder. Immune reconstitution was noted to occur at a significantly faster rate in the secondary recipients, and without the occurrence of graft-versus-host disease (GVHD), despite the presence of donor cells mismatched for 1 to 3 HLA antigens. This serial transplantation technique allows the primary recipient of HLA-mismatched donor cells to act as a functionally "HLA-matched" donor for subsequent affected siblings, and should be considered as a therapeutic option in families with congenital disorders.

The effect of proinflammatory cytokine gene and angiotensin-converting enzyme polymorphisms on erythropoietin requirements in patients on continuous ambulatory peritoneal dialysis.

BACKGROUND: The correction of anemia by recombinant human erythropoietin (rHuEPO) improves quality of life and prolongs life in end-stage renal failure. rHuEPO requirements for an individual are determined by a range of factors, including iron deficiency and inflammation. Single nucleotide polymorphisms in the promoter sequence of several proinflammatory cytokines have been shown, in different fields of medicine, to influence the cytokine response to different stimuli, with effects on clinical outcome. METHODS: The angiotensin-converting enzyme (ACE) insertion/deletion polymorphism and polymorphisms in the promoter regions of the genes for tumor necrosis factor alpha (-308 A/G), interleukin-6 (-174 G/C), and interferon gamma were examined for their association with rHuEPO requirements in 112 patients on continuous ambulatory peritoneal dialysis (CAPD). Genomic DNA was extracted from peripheral blood leukocytes and genotyping performed with ARMS-PCR methodology, with sequence-specific primers. We examined rHuEPO requirements and C-reactive protein at baseline and during a 6-month study period. RESULTS: We found no significant effect of proinflammatory cytokine polymorphisms on rHuEPO responsiveness. However, throughout the study, we observed that there was a significantly higher rHuEPO requirement in the II and ID ACE genotypes compared with the DD group, which remained an independent association following multivariate analysis. CONCLUSIONS: ACE insertion/deletion polymorphism may determine rHuEPO responsiveness in CAPD patients and should be considered in relative rHuEPO resistance.

Pretransplantation levels of C-reactive protein predict all-cause and cardiovascular mortality, but not graft outcome, in kidney transplant recipients.

BACKGROUND: Chronic inflammation, the common pathway that leads to cardiovascular disease and chronic allograft nephropathy after transplantation, is prevalent in patients with end-stage renal failure. We set out to investigate the hypothesis that enhanced pretransplantation C-reactive protein (CRP) levels and Chlamydia seropositivity, both markers of an altered immune response, would predict graft failure and mortality in patients receiving renal replacement therapy. METHODS: A retrospective study of 115 patients, based on CRP levels in pretransplantation serum (group 1, 0 to 5 mg/L; group 2, 5 to 10 mg/L; group 3, >10 mg/L), were investigated for the following end points: transplant rejection, graft failure, and all-cause and cardiovascular mortality. RESULTS: There were no correlations between CRP levels or Chlamydia seropositivity with respect to rejection rates or graft failure. Furthermore, there was no relationship between Chlamydia seropositivity and survival. All-cause and cardiovascular mortality were significantly greater in patients with CRP levels greater than 10 mg/L and 5 to 10 mg/L compared with those with CRP levels less than 5 mg/L. All-cause mortality rates were 5% in the 0-to-5-mg/L group, 20% in the 5-to-10-mg/L group, and 44% in the greater-than-10-mg/L group. With regard to cardiovascular mortality, death rates were 0% in the 0-to-5-mg/L group, 10% in the 5-to-10-mg/L group, and 22% in the greater-than-10-mg/L group. Univariate analysis of cardiovascular mortality and covariates showed a significant relationship with age (relative risk [RR], 1.07; P < 0.05), diabetes (RR, 5.6; P < 0.05), aspirin intake (RR, 0.2; P < 0.05), antihypertensive therapy (RR, 0.02; P < 0.05), and CRP level (RR, 11; P < 0.05), but CRP level remained the only significant predictor (RR, 1.19; P < 0.05) on multivariate analysis. CONCLUSION: Pretransplantation CRP level is independently associated with all-cause and cardiovascular mortality in our cohort of transplant recipients and may be a useful predictive marker in the follow-up of posttransplantation patients.

Angiotensin-converting enzyme gene polymorphism and erythropoietin requirement.

OBJECTIVES: To study the effect of angiotensin-converting enzyme (ACE) polymorphisms II, ID, and DD on erythropoietin (EPO) requirement in patients on continuous ambulatory peritoneal dialysis (CAPD) therapy. DESIGN: Retrospective observational study. SETTING: CAPD Unit, Royal London/St. Bartholomews Hospital, London, UK. PATIENTS: 46 patients on the transplant waiting list (age 20-70 years), on CAPD therapy for an average of 28 months, seen consecutively over a period of 3 months in the outpatients department. MAIN OUTCOME MEASURES: Primary end point: EPO dose requirement in different ACE genotypes. Secondary end points: C-reactive protein, ferritin, parathyroid hormone, Kt/V, duration of dialysis, folate, cause of renal failure, and whether or not patients were on ACE inhibitor therapy. RESULTS: There was a statistically significant difference (p < 0.05) in EPO requirement in the II/ID group compared to the DD group. The mean +/- standard error of EPO for the II/ID group was 144 +/- 15 U/kg/week, and for the DD group, 87 +/- 9 U/kg/week. The difference in EPO requirement could not be explained by age, C-reactive protein, ferritin, parathyroid hormone, Kt/V, duration of dialysis, folate, cause of renal failure, or whether or not patients were on ACE inhibitor therapy. CONCLUSION: In CAPD patients, ACE genotype has predictive value when determining the EPO dosage, as the III/ID genotype may be associated with a suboptimal response.