The combination of interferon alfa-2a (IFN alpha) and high-dose interleukin-2 (IL-2) is active in metastatic melanoma. The addition of cisplatin (CDDP) has resulted in response rates greater than ...50%. This study was performed to determine whether the addition of CDDP to a cytokine treatment regimen with IFN alpha and high-dose IL-2 influences survival of patients with metastatic melanoma.
Patients with advanced metastatic melanoma were randomly assigned to receive treatment with IFN alpha 10 x 10(6) U/m2 subcutaneously on days 1 through 5 and a high-dose intravenous decrescendo regimen of IL-2 on days 3 through 8 (18 mIU/ m2/6 hours, 18 mIU/m2/12 hours, 18 mIU/m2/24 hours, and 4.5 mIU/m2/24 hours x 3) without (arm A) or with (arm B) CDDP 100 mg/m2 on day 1. Treatment cycles were repeated every 28 days to a maximum of four cycles.
One hundred thirty-eight patients with advanced metastatic melanoma, of whom 87% had visceral metastases, were accrued for the trial. Both regimens were feasible in a multicenter setting. The objective response rate was 18% without and 33% with CDDP (P = .04). The progression-free survival was 53 days without and 92 days with CDDP (P = .02, Wilcoxon; P = .09, log-rank). There was no statistically significant difference in survival between treatment arms, with a median overall survival duration for all patients of 9 months.
The addition of CDDP to cytokine treatment with IFN alpha and IL-2 does not influence survival of patients with advanced metastatic melanoma, despite a significant increase in response rate and progression-free survival.
The Andes as mountain regions worldwide, provide fundamental resources, not only for the local population. Due to the topographic characteristics, the potential for natural hazards is higher than ...elsewhere. In these areas, assessments of climate change impacts and the development of adequate adaptation strategies therefore become particular important. The data basis, however, is often scarce. Moreover, perceptions of changes and needs are often divergent between national and local levels, which make the implementation of adaptation measures a challenge. Taking the Peruvian Andes as an example, this paper aims at initiating a discussion about scientific baseline and integrative concepts needed to deal with the adverse effects of climate change in mountain regions.
Summary Valproic acid (VPA), as one of the most widely prescribed antiepileptic drugs (AED) for many types of epilepsy in adults and children, is associated with weight gain, alteration of ...adipocytokine homeostasis, insulin resistance and Non-Alcoholic Fatty Liver Disease (NAFLD). Retinol-binding protein 4 (RBP4) and Glucagon-like peptide-1 (GLP-1) are considered as important new targets in modern type 2 diabetes mellitus therapy linked to insulin resistance, NAFLD and visceral obesity acting via peripheral or central mechanisms. We herein demonstrate the lack of an influence of VPA treatment on RBP4 and GLP-1 in otherwise healthy patients. In summary, the absence of any relationship with RBP4 and GLP-1 concentrations does not suggest a role of these novel insulin resistance parameters as potential regulators of glucose and fat metabolism during VPA-therapy.
Extemporaneous formulations broaden the spectrum of therapeutic options for topical treatment in particular and thus improve patient care. The latest amendment to the Regulation on the Operation of ...Pharmacies issued in 2012 brought about changes in prescribing and manufacturing practices. The aim of the present study was to assess the relevance of extemporaneous formulations in everyday clinical practice.
We used data from the German Institute for Drug Use Evaluation (DAPI) to analyze the prescribing practice for compounded preparations in Germany between the fourth quarter of 2011 and the third quarter of 2014. In doing so, we determined the total cost associated with extemporaneous formulations covered by statutory health insurance funds in the outpatient setting.
Approximately three out of ten prescriptions (30.54 %) by German dermatologists during the observation period were extemporaneous formulations. While dermatologists make up only 2.7 % of physicians working in the statutory health care system in Germany, they prescribe more than half of all compounded preparations (53.6 %). Each dermatologist prescribed an average of 270.4 formulations per quarter; that number was 13.5 (1.3 %) for all other medical specialties. On average, 1,983,687 extemporaneous formulations overall (1.3 % of all prescriptions) were prescribed per quarter, corresponding to a total cost of € 40,944,982 (0.55 %).
Apart from finished medicinal products, extemporaneous formulations play a key role in outpatient care. Based on the principles of evidence-based and patient-oriented medicine, the quality of compounded preparations and the prescribing practice of physicians (standardized vs. individual formulations) should be further investigated to optimize the quality of these preparations.
Large-scale semantic co-labeling of image sets Alvarez, Jose M.; Salzmann, Mathieu; Barnes, Nick
IEEE Winter Conference on Applications of Computer Vision,
2014-March
Conference Proceeding
As evidenced by video segmentation and cosegmentation approaches, exploiting multiple images is key to the success of visual scene understanding. With the availability of increasingly large sets of ...images, there is a clear need for methods that can efficiently analyze the similarities and structure across huge numbers of image pixels. Furthermore, to make effective use of this data, these similarities should not just be considered locally between neighboring pixels, but between all pairs of pixels across all images. In this paper, we tackle this challenging scenario by introducing a semantic co-labeling approach that performs efficient inference in a fully-connected CRF defined over the pixels, or superpixels, of an image set. Our experimental evaluation demonstrates that our approach yields improved accuracy while coming at no additional computation cost compared to performing segmentation sequentially on individual images. Furthermore, our formulation lets us perform inference over ten thousand images in a matter of seconds.
(1) Background: Refractory acute graft-versus-host disease (R-aGvHD) remains a leading cause of death after allogeneic stem cell transplantation. Survival rates of 15% after four years are currently ...achieved; deaths are only in part due to aGvHD itself, but mostly due to adverse effects of R-aGvHD treatment with immunosuppressive agents as these predispose patients to opportunistic infections and loss of graft-versus-leukemia surveillance resulting in relapse. Mesenchymal stromal cells (MSC) from different tissues and those generated by various protocols have been proposed as a remedy for R-aGvHD but the enthusiasm raised by initial reports has not been ubiquitously reproduced. (2) Methods: We previously reported on a unique MSC product, which was generated from pooled bone marrow mononuclear cells of multiple third-party donors. The products showed dose-to-dose equipotency and greater immunosuppressive capacity than individually expanded MSCs from the same donors. This product, MSC-FFM, has entered clinical routine in Germany where it is licensed with a national hospital exemption authorization. We previously reported satisfying initial clinical outcomes, which we are now updating. The data were collected in our post-approval pharmacovigilance program, i.e., this is not a clinical study and the data is high-level and non-monitored. (3) Results: Follow-up for 92 recipients of MSC-FFM was reported, 88 with GvHD ≥°III, one-third only steroid-refractory and two-thirds therapy resistant (refractory to steroids plus ≥2 additional lines of treatment). A median of three doses of MSC-FFM was administered without apparent toxicity. Overall response rates were 82% and 81% at the first and last evaluation, respectively. At six months, the estimated overall survival was 64%, while the cumulative incidence of death from underlying disease was 3%. (4) Conclusions: MSC-FFM promises to be a safe and efficient treatment for severe R-aGvHD.
At present, Lake Chad (∼ 13∘′ N, ∼ 14∘ E) is
a shallow freshwater lake located in the Sahel/Sahara region of central
northern Africa. The lake is primarily fed by the Chari–Logone river system
...draining a ∼ 600 000 km2 watershed in tropical Africa. Discharge
is strongly controlled by the annual passage of the intertropical convergence
zone (ITCZ) and monsoon circulation leading to a peak in rainfall during
boreal summer. During recent decades, a large number of studies have been
carried out in the Lake Chad Basin (LCB). They have mostly focused on a
patchwork of exposed lake sediments and outcrops once inhabited by early
hominids. A dataset generated from a 673 m long geotechnical borehole
drilled in 1973, along with outcrop and seismic reflection studies, reveal
several hundred metres of Miocene–Pleistocene lacustrine
deposits. CHADRILL aims to recover a sedimentary core spanning the Miocene–Pleistocene
sediment succession of Lake Chad through deep drilling. This record will
provide significant insights into the modulation of orbitally forced changes
in northern African hydroclimate under different climate boundary conditions
such as high CO2 and absence of Northern Hemisphere ice sheets. These
investigations will also help unravel both the age and the origin of the lake
and its current desert surrounding. The LCB is very rich in early hominid
fossils (Australopithecus bahrelghazali; Sahelanthropus tchadensis) of Late Miocene age. Thus, retrieving a sediment core from this
basin will provide the most continuous climatic and environmental record with
which to compare hominid migrations across northern Africa and has major
implications for understanding human evolution. Furthermore, due to its
dramatic and episodically changing water levels and associated depositional
modes, Lake Chad's sediments resemble maybe an analogue for lake systems that
were once present on Mars. Consequently, the study of the subsurface
biosphere contained in these sediments has the potential to shed light on
microbial biodiversity present in this type of depositional environment. We propose to drill a total of ∼ 1800 m of poorly to semi-consolidated
lacustrine, fluvial, and eolian sediments down to bedrock at a single
on-shore site close to the shoreline of present-day Lake Chad. We propose to
locate our drilling operations on-shore close to the site where the
geotechnical Bol borehole (13∘28′ N, 14∘44′ E) was
drilled in 1973. This is for two main reasons: (1) nowhere else in the Chad
Basin do we have such detailed information about the lithologies to be
drilled; and (2) the Bol site is close to the depocentre of the Chad Basin
and therefore likely to provide the stratigraphically most continuous
sequence.
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