Rapid rise in Effective Sea-Level in southwest Bangladesh: Its causes and contemporary rates

Evidence is presented from three estuarine tide gauges located in the
Sundarban area of southwest Bangladesh of relative sea level rise
substantially in excess of the generally accepted rates from altimetry, as
well as previous tide-gauge analyses. It is proposed that the difference
arises from the use of relative mean sea level (RMSL) to characterise the
present and future coastal flood hazard, since RMSL can be misleading in
estuaries in which tidal range is changing. Three tide gauges, one located in
the uninhabited mangrove forested area (Sundarban) of southwest
Bangladesh, the others in the densely populated polder zone north of the
present Sundarban, show rates of increase in RMSL ranging from 2.8 mm
a-1 to 8.8 mm a-1. However, these trends in RMSL disguise the fact that high
water levels in the polder zone have been increasing at an average rate of
15.9 mm a-1 and a maximum of 17.2 mm a-1. In an area experiencing tidal
range amplification, RMSL will always underestimate the rise in high water
levels; consequently, as an alternative to RMSL, the use of trends in high
water maxima or ‘Effective Sea Level Rise’ (ESLR) is adopted as a more
strategic parameter to characterise the flooding hazard potential. The rate
of increase in ESLR is shown to be due to a combination of deltaic
subsidence, including sediment compaction, and eustatic sea level rise, but
principally as a result of increased tidal range in estuary channels recently
constricted by embankments. These increases in ESLR have been partially
offset by decreases in fresh water discharge in those estuaries connected
to the Ganges. The recognition of increases of the effective sea level in the
Bangladesh Sundarban, which are substantially greater than increases in
mean sea level, is of the utmost importance to flood management in this
low-lying and densely populated area.

Implications of Intercellular Signaling for Radiation Therapy: A Theoretical Dose-Planning Study

Purpose
Recent in vitro results have shown significant contributions to cell killing from signaling effects at doses that are typically used in radiation therapy. This study investigates whether these in vitro observations can be reconciled with in vivo knowledge and how signaling may have an impact on future developments in radiation therapy.
Methods and Materials
Prostate cancer treatment plans were generated for a series of 10 patients using 3-dimensional conformal therapy, intensity modulated radiation therapy (IMRT), and volumetric modulated arc therapy techniques. These plans were evaluated using mathematical models of survival following modulated radiation exposures that were developed from in vitro observations and incorporate the effects of intercellular signaling. The impact on dose-volume histograms and mean doses were evaluated by converting these survival levels into "signaling-adjusted doses" for comparison.
Results
Inclusion of intercellular communication leads to significant differences between the signalling-adjusted and physical doses across a large volume. Organs in low-dose regions near target volumes see the largest increases, with mean signaling-adjusted bladder doses increasing from 23 to 33 Gy in IMRT plans. By contrast, in high-dose regions, there is a small decrease in signaling-adjusted dose due to reduced contributions from neighboring cells, with planning target volume mean doses falling from 74 to 71 Gy in IMRT. Overall, however, the dose distributions remain broadly similar, and comparisons between the treatment modalities are largely unchanged whether physical or signaling-adjusted dose is compared. Conclusions Although incorporating cellular signaling significantly affects cell killing in low-dose regions and suggests a different interpretation for many phenomena, their effect in high-dose regions for typical planning techniques is comparatively small. This indicates that the significant signaling effects observed in vitro are not contradicted by comparison with clinical observations. Future investigations are needed to validate these effects in vivo and to quantify their ranges and potential impact on more advanced radiation therapy techniques.

The addition of gemtuzumab ozogamicin to low-dose Ara-C improves remission rate but does not significantly prolong survival in older patients with acute myeloid leukaemia:results from the LRF AML14 and NCRI AML16 pick-a-winner comparison

The treatment of older patients with acute myeloid leukaemia, who are not considered suitable for conventional intensive therapy, is unsatisfactory. Low-dose Ara-C(LDAC) has been established as superior to best supportive care, but only benefits the few patients who enter complete remission. Alternative or additional treatments are required to improve the situation. This randomised trial compared the addition of the immunoconjugate, gemtuzumab ozogamicin (GO), at a dose of 5 mg on day 1 of each course of LDAC, with the intention of improving the remission rate and consequently survival. Between June 2004 and June 2010, 495 patients entered the randomisation. The addition of GO significantly improved the remission rate (30% vs 17%; odds ratio(OR) 0.48 (0.32-0.73); P=0.006), but not the 12 month overall survival (25% vs 27%). The reason for the induction benefit failing to improve OS was two-fold: survival of patients in the LDAC arm who did not enter remission and survival after relapse were both superior in the LDAC arm. Although the addition of GO to LDAC doubled the remission rate it did not improve overall survival. Maintaining remission in older patients remains elusive.