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Discussion: This is first head to head comparative trial showing that a rapid hike of CAB dose is not associated with earlier normalization of PRL or reduction in tumor volume as compared to conventional monthly hike.

There is no difference in the number of patients or duration required to achieve the composite end point. We obtained much earlier PRL normalization 8.

Rapid escalation of CAB was well tolerated. Conclusion: A weekly or a conventional 4 weekly escalation of CAB have a similar efficacy with regards to the achievement of normoprolactinemia and significant tumor shrinkage for macroprolactinoma. Cabergoline CAB is conventionally started at a dose of 0.

However,none of the studies previously have considered both of these parameters as a composite end point of treatment.

We conducted a randomized, prospective trial hypothesizing that rapid escalation of CAB doses, may help in both the earlier normalization of PRL and also significant shrinkage of tumor mass. CAB was started at a conventional dose of 0. In rapid escalation group B group, CAB was started at a dose of 0. PRL was measured by electrochemiluminescenceimmunoassay sandwich method.

Pituitary tumors were evaluated by a 3 Tmagnetic resonance imaging MRI scanner monthly till the 3rd month, and then 3 monthly until end point was achieved.

Visual field were assessed with automated perimeter weekly till 4 weeks and than 4 weekly until CEP was achieved. However, 38 patients completed a minimum follow-up of 24 weeks 19 in each group.

The baseline parameters in terms of age, gender, symptom duration, baseline prolactin levels, tumor volume, and duration of the follow-up were comparable. Normoprolactinemia was achieved in There was significant tumor shrinkage by There was no difference in the tumor shrinkage in either of the groups. The CEP was achieved in 14 patients in group A Moreover, there was no difference in the number of patients achieving the composite end point with either of the two regimens of CAB for the treatment of macroprolactinoma.

Previously, two studies including ours have shown that rapid escalation of CAB is associated with earlier normalization of PRL;[ 2 , 3 ] however,none of the studies had a comparative group.

Tumor shrinkage was Therapy may need to be individualized depending on the prevailing symptoms.

Similar observations have been made earlier, but the strategy of hiking the dose depending on tumor volume has not been practiced earlier. In our analysis, we forecast and compare twenty-first-century growth rates in expected annual exposure for US municipalities and four variables: population, housing units, property value, and road miles. We develop profiles of exposure as a function of flood height for each city-variable combination, and integrate these with projected local flood height probabilities over time under different carbon emissions and sea level scenarios Sect.

With the resulting curves, we assess the magnitude and rate of increases in annual expected exposure under different carbon emissions pathways, and identify cities exceeding different thresholds Sect. Finally, we discuss the limitations of this method, along with possible implications for adaptation strategies by policy makers and planners Sect.

Employing a bathtub model, we threshold each pixel in the resulting digital elevation models to produce inundation surfaces at 0.

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These surfaces are then refined by using connected component analysis to remove all low-lying subthreshold areas that the analysis indicates to be isolated by topography or levees from the ocean. These, and all other data sources used in this analysis, are listed for convenience in Table S9. Because these sources lack data on flood control structure height or condition, for simplicity and analytic tractability, we treat all structures as high and strong enough to protect against any flood that would meaningfully influence our results.

We also assume that no new protective structures will be built, because of the extreme uncertainty around whether, where and when any individual structure would be added.

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Some research has modeled future levee building decisions in the USA, but without the spatiotemporal resolution or confidence that would be required here Neumann et al. To develop our analysis of exposure, we use census block boundary, population, and housing data from the US census US Census Bureau , and recent property value PV estimates from Neumann et al.

We assume that population, housing unit, and PV density are zero over wetland areas delineated by the National Wetland Inventory US Fish and Wildlife Service , and compensate by proportionately increasing densities in the balance of each affected block population, housing or blockgroup PV area.

Since we use densities averaged over the dryland portions of census blocks population, housing or blockgroups PV , our results would be biased if structures tend to be concentrated at higher or lower elevations within these units.

To ensure that the results of this analysis are not overly sensitive to our uniform dryland density assumption, we perform a similar assessment of road exposure using spatially explicit road centerline data from the US Census. We reason that road density should correlate with development, and thus, results for roads should appear similar to other results, assuming that there is no elevation bias of structures within blocks or blockgroups.

Rapid Escalation

In this context, for consistency with our approach for other variables, we do not include roads over wetland areas in the exposure assessment we assume that they are elevated. We compute total population, housing unit, road length, and PV exposed under each inundation surface, and apply cubic Hermite interpolation to estimate any intermediate exposure values between the 0.

While we assess exposure given development as it exists today, population is likely to grow in low-lying coastal areas over the coming decades Hauer et al. However, projecting growth with the high spatiotemporal resolution needed for the present analysis would add large uncertainties and require major, untested assumptions concerning behavior and adaptation measures in the face of changing flood frequencies. To mitigate the concern that static populations are nonetheless unrealistic, we primarily consider percent rather than absolute exposure within each municipality.

This approach also better reflects the significance of the threat relative to each place as a whole and how it is developed today and allows us to more easily compare across municipalities.

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