Objective To evaluate the association between lymphopenia and survival in women with cervical cancer treated with primary chemoradiation. Methods A single institution, retrospective analysis of patients with stage IB2-IVA cervical cancer who received upfront chemoradiation from 1998 to 2013 was performed. Complete blood counts from pre-treatment to 36 months post-treatment were analyzed. Lymphopenia and known prognostic factors were evaluated for an association with progression-free (PFS) and overall survival (OS). Results Seventy-one patients met study criteria for whom 47 (66%) had a documented total lymphocyte count (TLC) two months after initiating chemoradiation. FIGO stage distribution was 6% Stage I, 46% Stage II, 45% Stage III and 3% Stage IV. Pre-treatment TLC was abnormal (<1000 cells/mm3) in 15% of patients. The mean reduction in TLC was 70% two months after initiating chemoradiation. Severe post-treatment lymphopenia (TLC <500 cells/mm3) was observed in 53% of patients; they experienced inferior median OS (21.2 vs 45.0 months, P = 0.03) and similar 25th percentile PFS (6.3 vs 7.7 months, P = 0.06) compared to patients without severe lymphopenia. Multivariate analysis demonstrated pre-treatment TLC ≥1000 cells/mm3 and post-treatment TLC >500 cells/mm3 had a 77% (HR: 0.23; 95% CI 0.05–1.03; P = 0.053) and 58% decrease in hazards of death (HR: 0.42; 95% CI 0.12–1.46; P = 0.17) respectively. Conclusion More than half of cervical cancer patients treated with chemoradiation experienced severe and prolonged lymphopenia. Although statistical significance was not reached, the findings suggest that pre- and post-treatment lymphopenia may be associated with decreased survival. Further research is warranted, given that lymphopenia could be a reversible prognostic factor.

The role of radiative forcings and climate feedbacks on global cooling over the last millennium is quantified in the CMIP5–PMIP3 transient climate model simulations. Changes in the global energy budget over the last millennium are decomposed into contributions from radiative forcings and climate feedbacks through the use of the approximate partial radiative perturbation method and radiative kernels. Global cooling occurs circa 1200–1850 CE in the multimodel ensemble mean with pronounced minima corresponding with volcanically active periods that are outside the range of natural variability. Analysis of the global energy budget during the last millennium indicates that Little Ice Age (LIA; 1600–1850 CE) cooling is largely driven by volcanic forcing (comprising an average of 65% of the total forcing among models), while contributions due to changes in land use (13%), greenhouse gas concentrations (12%), and insolation (10%) are substantially lower. The combination of these forcings directly contributes to 47% of the global cooling during the LIA, while the remainder of the cooling arises from the sum of the climate feedbacks. The dominant positive feedback is the water vapor feedback, which contributes 29% of the global cooling. Additional positive feedbacks include the surface albedo feedback (which contributes 7% of the global cooling and arises owing to high-latitude sea ice expansion and increased snow cover) and the lapse rate feedback (which contributes an additional 7% of the global cooling and arises owing to greater cooling near the surface than aloft in the middle and high latitudes).

The scale-up of HIV antiretroviral therapy in recent years has led to a rapid increase in CD4 and CD4% count capacity to meet the diagnostic needs of staging and monitoring disease progression and treatment efficacy in adults and infants. The speed of implementation of this technology has been unrivalled in recent years and has met challenges with technology selection, laboratory infrastructure development, human resource limitations, cost-effectiveness, instrument maintenance, and ensuring testing access and quality. The lessons learned from dealing with these challenges have helped strengthen existing laboratory systems for other diagnostics. They may also facilitate the implementation of new diagnostics in future. q

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