Ultrathin Alvarez lens system actuated by artificial muscles.

A key feature of Alvarez lenses is that they may be tuned in focal length using lateral rather than axial translation, thus reducing the overall length of a focus-tunable optical system. Nevertheless the bulk of classical microsystems actuators limits further miniaturization. We present here a new, ultrathin focus-tunable Alvarez lens fabricated using molding techniques and actuated using liquid crystal elastomer (LCE) artificial muscle actuators. The large deformation generated by the LCE actuators permits the integration of the actuators in-plane with the mechanical and optical system and thus reduces the device thickness to only 1.6 mm. Movement of the Alvarez lens pair of 178 µm results in a focal length change of 3.3 mm, based on an initial focal length of 28.4 mm. This design is of considerable interest for realization of ultraflat focus-tunable and zoom systems.

[Changes in therapy for breast cancer patients as a result of mammography screening. An analysis of Bavarian cancer registry data from 2000 to 2008]. / Veränderungen der Therapie des Mammakarzinoms in Bayern seit Einführung des Mammografie-Screenings. Eine Analyse bayerischer Krebsregisterdaten der Jahre 2000 bis 2008.

PURPOSE: A quality controlled mammography screening programme was initiated at the end of 2003 in Bavaria, a region with 12.5 million inhabitants, and transferred over to the national screening programme at the end of 2006. The purpose of this study was to evaluate immediate population-based consequences of mammography screening on breast cancer therapy. METHODS: Data from 75 475 breast cancer cases, diagnosed between 2000 and 2008 and registered in one of the 6 Bavarian clinical cancer registries were analysed. 51.4% of these patients were between 50 and 69 years of age and therefore the target population for screening. Trends of prognostic factors and standard therapies were calculated for 3 age groups (≤49 years, 50-69 years, ≥70 years) by means of annual percentages as well as 95%-confidence intervals for the percent difference between 2000 and 2008 (year of diagnosis). For interpretation of therapy trends, logistic regression models were calculated. RESULTS: Therapy trends showed that the increasingly favourable stage distribution may have resulted in the reduction of more radical surgical methods such as mastectomy (2000: 32.6%; 2008: 19.6%) or axillary dissection (89.0% vs. 37.0%), especially for women aged 50-69. An increase of radiation therapies (59.7% vs. 66.6%) can be explained to some extent by the increase in breast conserving surgeries. The shift to more favourable prognostic factors led, in accordance with the guidelines, to an increase of the proportion of singular endocrine therapies (28.5% vs. 40.7%), a decrease of chemotherapies (20.4% vs. 13.1%) and therefore to more gentle systemic therapies overall. These trends strengthened in the years following the introduction of screening, with a simultaneous rise of screening participants in the target population. CONCLUSION: The introduction of mammography screening in Bavaria has already shown the expected trend towards more favourable prognostic factors. Among other things, this could be a reason for the increasing use of more gentle therapies. Whether the screening in Bavaria leads to a mortality reduction, has to be analysed on the basis of an initial comparison of participation status followed by the trends in mortality thereafter.

Twelve testable hypotheses on the geobiology of weathering.

Critical Zone (CZ) research investigates the chemical, physical, and biological processes that modulate the Earth's surface. Here, we advance 12 hypotheses that must be tested to improve our understanding of the CZ: (1) Solar-to-chemical conversion of energy by plants regulates flows of carbon, water, and nutrients through plant-microbe soil networks, thereby controlling the location and extent of biological weathering. (2) Biological stoichiometry drives changes in mineral stoichiometry and distribution through weathering. (3) On landscapes experiencing little erosion, biology drives weathering during initial succession, whereas weathering drives biology over the long term. (4) In eroding landscapes, weathering-front advance at depth is coupled to surface denudation via biotic processes. (5) Biology shapes the topography of the Critical Zone. (6) The impact of climate forcing on denudation rates in natural systems can be predicted from models incorporating biogeochemical reaction rates and geomorphological transport laws. (7) Rising global temperatures will increase carbon losses from the Critical Zone. (8) Rising atmospheric P(CO2) will increase rates and extents of mineral weathering in soils. (9) Riverine solute fluxes will respond to changes in climate primarily due to changes in water fluxes and secondarily through changes in biologically mediated weathering. (10) Land use change will impact Critical Zone processes and exports more than climate change. (11) In many severely altered settings, restoration of hydrological processes is possible in decades or less, whereas restoration of biodiversity and biogeochemical processes requires longer timescales. (12) Biogeochemical properties impart thresholds or tipping points beyond which rapid and irreversible losses of ecosystem health, function, and services can occur.

[Ten years of epidemiological cancer registration in Bavaria]. / Zehn Jahre Krebsregistrierung in Bayern.

For a large territorial state like Bavaria only a decentralised cancer registration structure promises successful results: in the form of regional clinical cancer registries and--using the clinical registration as a base--one population-based registry. After ten years of epidemiological cancer registration in Bavaria it can now be shown that the chosen registration concept has proved itself. Currently the completeness of cancer notifications exceeded the international recommended threshold of 90%. A largely complete data stock is available for the years of diagnosis from 2004 to 2005. The task sharing between clinical and population-based cancer registries avoids double registration of data. Both types of registries are supporting physicians and hospitals with a wide palette of services. Together they enable transparency of cancer occurrence as well as transparency of health care for tumour patients.

14C-dead living biomass: evidence for microbial assimilation of ancient organic carbon during shale weathering.

Prokaryotes have been cultured from a modern weathering profile developed on a approximately 365-million-year-old black shale that use macromolecular shale organic matter as their sole organic carbon source. Using natural-abundance carbon-14 analysis of membrane lipids, we show that 74 to 94% of lipid carbon in these cultures derives from assimilation of carbon-14-free organic carbon from the shale. These results reveal that microorganisms enriched from shale weathering profiles are able to use a macromolecular and putatively refractory pool of ancient organic matter. This activity may facilitate the oxidation of sedimentary organic matter to inorganic carbon when sedimentary rocks are exposed by erosion. Thus, microorganisms may play a more active role in the geochemical carbon cycle than previously recognized, with profound implications for controls on the abundance of oxygen and carbon dioxide in Earth's atmosphere over geologic time.

Lymph node involvement in renal cell carcinoma and survival chance by systematic lymphadenectomy.

BACKGROUND: The value of systematic lymphadenectomy has been a matter of great controversy for a long period of time. A recently published paper of a retrospective autopsy study generally doubts its therapeutic effectiveness, arguing that positive lymph nodes are nearly always associated with distant metastases. PATIENTS AND METHODS: Between 1974 and 1993 1035 patients suffering from renal cell carcinoma with stages from cT 1 to 4, cM 0 were treated with curative intention. 51% underwent radical abdominal tumour nephrectomy with systematic lymphadenectomy (n = 531, group A). In 199 patients (19%, group B) only macroscopically suspect lymph nodes were removed surgically. All other patients underwent radical lumbar tumour nephrectomy without lymphadenectomy (n = 305, 29%, group C). RESULTS: Mean age of group A was 55.5 +/- 10 years, B 60.3 +/- 11 and C 66.5 +/- 11. Median follow-up for all groups was 115 +/- 63 months. Median amount of removed lymph nodes was 18 in group A, 6 in group B and 3 in group C. N-categories for each group were pN 1: 4%, 2%, 1%; pN 2: 7%, 5%, 1%; pN 3: 3%, 2, %, 1%; pN x: 0%, 35%, 67% respectively. Group A with systematic lymphadenectomy had the least favourable tumour stage overall. Nevertheless long-term survival of this group is more favourable with 57% +/- 6 when compared to group B with 50 +/- 12% and C with 44% +/- 9%. 20 (27%) of the 75 lymph node positive patients of group A who have been followed-up for more than 5 years are still alive. CONCLUSIONS: At least 4% of all patients benefit from extensive lymphadenectomy. This may only be a relatively small proven effect for the entire patient collective, but for a single lymph node positive patient this is an undoubtedly significant additional chance of survival especially when one notes that presently there is no curative adjuvant therapy.

[Long-term experience with percutaneous endoscopic controlled gastrostomy (PEG) in ENT tumor patients]. / Langzeiterfahrung mit der perkutanen endoskopisch kontrollierten Gastrostomie (PEG) bei HNO-Tumorpatienten.

Percutaneous endoscopically controlled gastrostomy (PEG) enables patients suffering from a tumor of the upper aerodigestive tract to receive direct gastric feedings. The procedure also avoids the social stigma of a nasal feeding tube. The results of 630 PEG procedures used in 555 patients suffering from various head and neck cancers are reported. The mean age of the patients was 58.0 years with a range from 11 to 92 years. The PEG procedure was carried out under local anesthesia in 60% of the cases and with general anesthesia in 40%. In 512 patients the initial PEG procedure was successful while 43 of the patients require a second PEG procedure after loss of the PEG. In 19 patients the PEG procedure was not successful because of tumor obstruction or it was not possible to perform endoscopy. Twenty-four patients were successfully treated in a second or third session. Although 97% (n = 563) of all 555 patients and 92% (n = 579) of all PEG procedures were successful. The mean duration of PEG use was 243 (range: 0-2271 days). In 66 patients (10.5%) complications occurred but severe complications developed in only 8 patients (1.3%). Operative interventions were necessary in two cases. No deaths resulted from the PEG. These findings show that the PEG technique is safe to do with only few complications when performed by a skilled team.

Prognosis of high dose chemotherapy/autologous bone marrow transplantation candidates not receiving this treatment after failure of primary therapy of Hodgkin's disease.

In a multicenter study on the therapy of Hodgkin's disease, in 88 out of 297 patients with primary advanced stages IIIB/IV, a failure to the treatment with the alternating chemotherapy COPP/ABVD +/- radiation was recorded. The cause of failure was as follows: tumor progression under current therapy (PD) 23/88, partial response at the end of therapy (PR) 28/88, early nodal relapses 13/88, late nodal relapses 16/88, extranodal relapses 7/88, undetermined localization 1/88.36 months after manifestation of the failure to treatment, 45% of all patients were still alive. In cases of primary PD the prognosis was the worst of all. Only 1/23 of these patients received a long-term continuous complete remission (cCR) with the salvage therapy. 11 patients with only a nodal relapse received a cCR with irradiation alone. These cases could be regarded as low risk relapses. For the high risk relapse group (n = 57) an indication for high dose chemotherapy with subsequent autologous bone marrow transplantation (HDC/ABMT) would have been imperative, following the present-day definition. The probability of survival of these patients who, however, only received a conventional salvage therapy was up to 38% (95% confidence interval 22-54%). Comparing these data with the literature our results seem not to be substantially worse than those for patients who underwent HDC/ABMT. Only in a randomized comparison can the decision be made on whether HDC/ABMT would be superior to high dose conventional chemotherapy supported by hematopoietic growth factors. It is suggested that such a therapy study be performed as soon as possible.

[Recurrence of Hodgkin's disease after advanced primary stages. German Hodgkin's Study Group]. / Morbus-Hodgkin-Rezidive nach primär fortgeschrittenen Stadien. Deutsche Hodgkin-Studiengruppe.

In a multicentre study on the treatment of Hodgkin's disease, 88 out of 297 patients with primary advanced stages IIIB/IV failed to respond to alternating COPP/ABVD chemotherapy +/- radiotherapy. They may be broken down as follows: tumour progression under current therapy (PD) 23/28, partial remission at the end of treatment (PR) 28/88, early nodal recurrence 13/88, late nodal recurrence 15/88, extranodal recurrence 7/88, unclear localisation 1/88. Thirty-six months after noting failure of treatment, 45% of all patients were still alive. The prognosis was poorest in the case of primary PD. Only 1/23 of these patients experience lasting complete remission thanks to salvage treatment (cCR). Eleven patients with an exclusively nodal recurrence experienced a cCR on treatment with radiation alone, and may be considered a low-risk recurrence group. For a high-risk recurrence group (n = 57), indication for high-dose chemotherapy with subsequent autologous bone marrow transplantation (HDC/ABMT) should have been recognized on the basis of the present definition. The survival probability of these patients, who only received conventional salvage treatment, was 38% after 30 months (95% confidence limit, 22 to 54%). These data would not appear to be appreciably poorer than those reported in the literature for comparable patients receiving HDC/ABMT. Only a randomized comparison would be capable of showing whether HDC/ABMT is superior to high-dose conventional chemotherapy with haematopoietic growth factors. It is proposed that such a therapeutic trial should be initiated as soon as possible.

Chemotherapy of Hodgkin's lymphoma with alternating cycles of COPP (cyclophosphamide, vincristin, procarbazine, prednisone) and ABVD (doxorubicin, bleomycin, vinblastine and dacarbazine). Results of the HD1 and HD3 trials of the German Hodgkin Study Group.

Untreated patients with Hodgkin's lymphoma in stages I-IIIA with risk factors (large mediastinal mass, massive splenic involvement, extranodal disease) were entered into the HD1 protocol and received a combined chemo-radiotherapy [2 X (COPP + ABVD) + 40 Gy extended field irradiation (EF) vs 2 X (COPP + ABVD) + 20 Gy EF]. Patients in stages IIIB/IV (HD3 protocol) received induction chemotherapy [3 X (COPP + ABVD)] and were randomized into consolidation by radiotherapy [20 Gy involved field irradiation (IF)] vs chemotherapy [1 X (COPP + ABVD)]. Seventy-three of 89 evaluable patients (82%) treated according to the HD1 protocol achieved a complete remission. Freedom from progression and survival of patients in stages I-IIIA with risk factors treated according to HD1 were no worse than those of patients in stages I and II without risk factors who received only radiotherapy. Eighty-six of 137 patients (63%) treated according to the HD3 protocol achieved complete remission after induction chemotherapy with COPP + ABVD. This is significantly better than the 31% complete remission rate observed in a previous pilot study with COPP alone (P less than 0.01). Including salvage therapy (radiotherapy in case of persisting nodal disease; chemotherapy with 4 X CEVD in case of persisting disseminated disease), a total of 76% complete remissions in stages IIIB/IVAB were achieved. A high erythrocyte sedimentation rate (greater than 80 mm h-1) was the most significant risk factor for achieving freedom from progression.

[Therapy of Hodgkin's lymphomas. Results of the German Hodgkin's Disease Study Group]. / Therapie der Hodgkin-Lymphome. Ergebnisse der Deutschen Hodgkin-Studiengruppe.

Between July 1983 and May 1987 143 untreated patients with Hodgkin's lymphoma in stages I-IIIA with risk factors qualified for the HD1 protocol, and 230 patients in stages IIIB/IV qualified for HD3. Patients in HD1 received a combined chemo-radiotherapy (2 x COPP + ABVD + 20 Gy EF vs. 40 Gy EF). Patients in HD3 received induction chemotherapy (3 x COPP + ABVD) and were randomized into consolidation by radiotherapy (20 Gy IF) vs. chemotherapy (1 x COPP + ABVD). In HD1, 73 of 89 evaluable patients (82%) achieved a complete remission. The survival of patients in stages I-IIIA with risk factors treated according to HD1 is as good as the survival of patients in stages I and II without risk factors. In HD3, 86 of 137 patients (63%) achieved complete remission after induction chemotherapy with 3 x COPP + ABVD. This is significantly better than the 31% complete remission rate observed in a pilot study with COPP alone (p less than 0.01). Including salvage therapy (radiotherapy in case of persisting nodal disease; chemotherapy with 4 x CEVD in case of persisting disseminated disease), a total of 76% complete remissions in stages IIIB/IVAB were achieved. An ESR greater than 80 mm/h was the most significant single risk factor in stages IIIB/IV for induction of CR and freedom from progression.