Prostate cancer treatment with Irreversible Electroporation (IRE): Safety, efficacy and clinical experience in 471 treatments.

BackgroundIrreversible Electroporation (IRE) is a novel image-guided tissue ablation technology that induces cell death via very short but strong pulsed electric fields. IRE has been shown to have preserving properties towards vessels and nerves and the extracellular matrix. This makes IRE an ideal candidate to treat prostate cancer (PCa) where other treatment modalities frequently unselectively destroy surrounding structures inducing severe side effects like incontinence or impotence. We report the retrospective assessment of 471 IRE treatments in 429 patients of all grades and stages of PCa with 6-year maximum follow-up time.Material and findingsThe patient cohort consisted of low (25), intermediate (88) and high-risk cancers (312). All had multi-parametric magnetic resonance imaging, and 199 men had additional 3D-mapping biopsy for diagnostic work-up prior to IRE. Patients were treated either focally (123), sub-whole-gland (154), whole-gland (134) or for recurrent disease (63) after previous radical prostatectomy, radiation therapy, etc. Adverse effects were mild (19.7%), moderate (3.7%) and severe (1.4%), never life-threatening. Urinary continence was preserved in all cases. IRE-induced erectile dysfunction persisted in 3% of the evaluated cases 12 months post treatment. Mean transient IIEF-5-Score reduction was 33% within 12-month post IRE follow-up and 15% after 12 months. Recurrences within the follow-up period occurred in 10% of the treated men, 23 in or adjacent to the treatment field and 18 outside the treatment field (residuals). Including residuals for worst case analysis, Kaplan Maier estimation on recurrence rate at 5 years resulted in 5.6% (CI95: 1.8-16.93) for Gleason 6, 14.6% (CI95: 8.8-23.7) for Gleason 7 and 39.5% (CI95: 23.5-61.4) for Gleason 8-10.ConclusionThe results indicate comparable efficacy of IRE to standard radical prostatectomy in terms of 5-year recurrence rates and better preservation of urogenital function, proving the safety and suitability of IRE for PCa treatment. The data also shows that IRE, besides focal therapy of early PCa, can also be used for whole-gland ablations, in patients with recurrent PCa, and as a problem-solver for local tumor control in T4-cancers not amenable to surgery and radiation therapy anymore

Characterizing cross‐linking within polymeric biomaterials in the SEM by secondary electron hyperspectral imaging

A novel capability built upon secondary electron (SE) spectroscopy provides an enhanced cross‐linking characterization toolset for polymeric biomaterials, with cross‐linking density and variation captured at a multiscale level. The potential of SE spectroscopy for material characterization has been investigated since 1947. The absence of suitable instrumentation and signal processing proved insurmountable barriers to applying SE spectroscopy to biomaterials, and consequently, capturing SE spectra containing cross‐linking information is a new concept. To date, cross‐linking extent is inferred from analytical techniques such as nuclear magnetic resonance (NMR), differential scanning calorimetry, and Raman spectroscopy (RS). NMR provides extremely localized information on the atomic scale and molecular scale, while RS information volume is on the microscale. Other methods for the indirect study of cross‐linking are bulk mechanical averaging methods, such as tensile and compression modulus testing. However, these established averaging methods for the estimation of polymer cross‐linking density are incomplete because they fail to provide information of spatial distributions within the biomaterial morphology across all relevant length scales. The efficacy of the SE spectroscopy capability is demonstrated in this paper by the analysis of poly(glycerol sebacate)‐methacrylate (PGS‐M) at different degrees of methacrylation delivering new insights into PGS‐M morphology

Tensegrity modelling and the high toughness of spider dragline silk

This work establishes a tensegrity model of spider dragline silk. Tensegrity systems are ubiquitous in nature, being able to capture the mechanics of biological shapes through simple and effective modes of deformation via extension and contraction. Guided by quantitative microstructural characterization via air plasma etching and low voltage scanning electron microscopy, we report that this model is able to capture experimentally observed phenomena such as the Poisson effect, tensile stress-strain response, and fibre toughness. This is achieved by accounting for spider silks’ hierarchical organization into microfibrils with radially variable properties. Each fibril is described as a chain of polypeptide tensegrity units formed by crystalline granules operating under compression, which are connected to each other by amorphous links acting under tension. Our results demonstrate, for the first time, that a radial variability in the ductility of tensegrity chains is responsible for high fibre toughness, a defining and desirable feature of spider silk. Based on this model, a discussion about the use of graded tensegrity structures for the optimal design of next-generation biomimetic fibres is presented

Impact on Children and Families of the Deepwater Horizon Oil Spill: Preliminary Findings of the Coastal Population Impact Study

Although the ruptured Deepwater Horizon oil well was capped on July 15, 2010, an estimated 3 to 5 million barrels of oil spilled in to the Gulf of Mexico over a three-month period. Several surveys prior to the capping of the well documented the concerns and immediate effects of the oil spill on coastal residents. One report by a team of LSU sociologists highlighted the anxiety caused by the oil spill - nearly 60% of the 925 coastal Louisiana residents interviewed said they were almost constantly worried by the oil spill. As the "acute phase" of the oil spill transitions to a longer-term "chronic phase," researchers at Columbia University's National Center for Disaster Preparedness, in collaboration with the Children's Health Fund and The Marist Poll, interviewed over 1,200 coastal residents in Louisiana and Mississippi, with a particular focus on the short- and potential long-term impact of the disaster on children. This study was informed by work the researchers have done post-Katrina as part of the Gulf Coast Child & Family Health Study, which has documented the enduring effects on impacted populations in the two states, particularly children

Spinning beta silks requires both pH activation and extensional stress

Synthetic silk production has undergone significant technological and commercial advances over the past 5 years, with fibers from most labs and companies now regularly matching the properties of natural silk by one metric or another. Yet the fundamental links between silk protein processing and performance remain largely unresolved and fiber optimization is commonly achieved through non-natural methods. In an effort to address this challenge, data that closes this loop of processing and performance is presented by spinning a native silk feedstock ex vivo into a near-native fiber using just two naturally occurring parameters; pH activation and extensional flow (i.e., spinning rate). This allows us to link previous experimental and modelling hypothesis surrounding silk's pH responsiveness directly to multiscale hierarchical structure development during spinning. Finally, fibers that match, and then exceed, natural silk's mechanical properties are spun and understood by rate of work input. This approach not only provides energetic insights into natural silk spinning and controlled protein denaturation, but is believed will help interpret and improve synthetic silk processing. Ultimately, it is hoped that these results will contribute towards novel bioinspired energy-efficient processing strategies that are driven by work input optimization and where excellent mechanical properties are self-emergent

Second Wind: The Impact of Hurricane Gustav on Children and Families Who Survived Katrina

The category 2 Hurricane Gustav made landfall on the Louisiana Coast on Sept. 1, 2008, nearly three years to the day after Hurricane Katrina, resulting in an evacuation of approximately 2 million people and considerable property damage. Although it did not match the intensity or consequence of Hurricane Katrina, the experience of anticipating and responding to Hurricane Gustav had the potential to trigger emotional and physical consequences among a population previously traumatized or displaced by Hurricane Katrina. Gustav also had the potential to exert a considerable impact upon the overall economic, social, and emotional recovery of these populations. The Gulf Coast Child and Family Health Study (G-CAFH), a randomly-sampled post-Katrina longitudinal cohort study of 1,079 displaced and impacted households in Louisiana and Mississippi, was uniquely positioned to examine the evolving impact of Gustav upon a previously traumatized population. G-CAFH researchers were in the final stages of the third round of interviews with the study group when Hurricane Gustav struck, thus allowing for comparable pre- and post-event data for approximately 700 respondent households. Further information on the study, including previous reports and peer-reviewed research articles, may be found at www.gcafh.org. In particular, the research team was interested in the following issues: Evacuation: People's response to the event itself -- did they evacuate, and if so, where and how did they evacuate? How did people decide whether to evacuate or not? For those who did, what was the economic impact of the evacuation? Recovery Impact: What was the impact on post-Katrina recovery amongst this group, particularly since Hurricane Gustav may have set some people even further back in their efforts to recover their homes and their lives? Psychological Impact: What was the emotional impact on adults and children: among adults, did Hurricane Gustav trigger Katrina-related post-traumatic stress disorder symptoms? Among children, did Hurricane Gustav lead to newly experienced behavioral or emotional problems? Health Effects: What were the health consequences of Hurricane Gustav on children, particularly those who needed access to medications and medical care? Within three weeks of Hurricane Gustav, the G-CAFH field team had reassembled after their own evacuation and begun re-contacting the 718 respondents whom they had recently interviewed as part of the third round of the study. Of these 718 respondents, 528 were located and interviewed (a 73.5% retention rate). Respondents received a $20 gift card for participating in this study supplement, which had received approval by the Columbia University Medical Center Institutional Review Board

Teores de matéria seca, proteína bruta, carboidratos solúveis e extrato etéreo das silagens de tres genótipos de girassol (Helianthus annuus L.) com aditivos em sete diferentes épocas de abertura.

O objetivo deste experimento foi avaliar os teores de materia seca (MS), proteína bruta (PB), carboidratos soluveis (CHO) e extrato etereo (EE) das silagens de tres genotipos: M 734, Rumbosol 91 e a variedade V2000, enriquecidas com ureia (U), carbonato de calcio (CC), ureia mais carbonato de calcio (U*CC); e inoculante bacteriano (IB), sendo tambem ensilado material original sem aditivo que serviu como silagem testemunha (T). Foram utilizados silos de laboratorio de PVC, abertos com um, tres, cinco, sete, 14, 28 e 56 dias de ensilados. As silagens de genotipos M734 foram as que apresentaram os maiores teores de MS comparadas as silagens do Rumbosol 91 e este maior que o V2000. A adicao somente de U resultou em silagens com teores de PB superiores as silagens T e foram semelhantes entre si nos diferentes dias de abertura. Os teores de CHO soluveis variaram de 0,03% a 3,86%, sendo que as silagens T e com aditivos do genotipo M734 apresentaram no dia de abertura um teores significativamente superiores ao Rumbosol 91 e ao V2000. O IB nao promoveu uma rapida queda nos teores de CHO soluveis como esperado. os teores de EE foram estatisticamente superiores para os genotipos V2000 e M734 em relacao ao Rumbosol 91 e nao apresentaram diferenca com a utilizacao dos aditivos. Concluindo, as silagens de girassol avaliadas apresentaram baixos teores de MS e apenas o uso de ureia promoveu alteracoes aumentando o teor de proteina bruta das silagens dentro dos parametros avaliados

Maintenance of Leukemia-Initiating Cells Is Regulated by the CDK Inhibitor Inca1

Functional differences between healthy progenitor and cancer initiating cells may provide unique opportunities for targeted therapy approaches. Hematopoietic stem cells are tightly controlled by a network of CDK inhibitors that govern proliferation and prevent stem cell exhaustion. Loss of Inca1 led to an increased number of short-term hematopoietic stem cells in older mice, but Inca1 seems largely dispensable for normal hematopoiesis. On the other hand, Inca1-deficiency enhanced cell cycling upon cytotoxic stress and accelerated bone marrow exhaustion. Moreover, AML1-ETO9a-induced proliferation was not sustained in Inca1-deficient cells in vivo. As a consequence, leukemia induction and leukemia maintenance were severely impaired in Inca1−/− bone marrow cells. The re-initiation of leukemia was also significantly inhibited in absence of Inca1−/− in MLL—AF9- and c-myc/BCL2-positive leukemia mouse models. These findings indicate distinct functional properties of Inca1 in normal hematopoietic cells compared to leukemia initiating cells. Such functional differences might be used to design specific therapy approaches in leukemia

Valores de pH e teores de nitrogênio amoniacal das silagens de três genótipos de girassol (Helianthus annuus L.) com aditivos durante o processo fermentativo.

Silagens de tres genotipos de girassol: M 734, Rumbosol 91 e a variedade V2000, foram enriquecida com 0,5% de ureia (U); 0,5% de carbonato de calcio (CC); 0,5% de ureia mais 0,5% de carbonato de calcio (U+CC); inoculante bacteriano (IB), sendo também ensilado material original sem aditivo que serviu como silagem testemunha (T), visando avaliar os efeitos nos valores de pH e nitrogenio amoniacal (N-NH)(. Foram utilizados silos de laboratório de PVC, abertos nos dias um, tres, cinco, sete, 14, 28 e 56 de ensilados. A adicao de U as silagens acarretou em pH numericamente mais elevado em todas as silagens a partir do terceiro dia de abertura quando comparado a silagem T, porem as diferenças estatisticas observadas nao foram consistentes. Os maiores valores de pH foram verificados nas silagens de girassol tratadas com U+CC (78,8% N-NH3/NT), que estabilizou a producao de nitrogenio amoniacal no decimo quarto dia de abertura com 69,3% N.NH3/NT. A penas a adicao de ureia associada a carbonato de calcio apresentou a mesma resposta para os parametros avaliados nos tres genotipos. Contudo, deve-se ter cautela na recomendacao destes aditivos para silagem de girassol, pois estes altos valores encontrados podem estar relacionados a fermentacao indesejaveis no silo

Teores de ácidos graxos voláteis e acido láctico das silagens de girassol (Helianthus annuus L.) tratadas com aditivos em seis diferentes épocas de abertura.

O objetivo deste trabalho foi avaliar os teores de acidos organicos das silagens de tres genotipos de girassol (M734, Rumbosol 91 e variedade V2000) enriquecida com os seguintes aditivos 0,5% de ureia (U); 0,5% de carbonato de calcio (CC); 0,5% de ureia mais 0,5 de carbonato de calcio (U*CC); inoculante bacteriano (IB) comercial. Também foi ensilado material original sem aditivos que serviu como silagem testemunha (T), sendo utilizados 180 silos de laboratorio de PVC, os quais foram abertos nos dias: um, tres, cinco, sete, 28 e 56 dias. Foram determinados os teores dos acidos lactico, acetico, propionico e butirico por cromatografia gasosas. As silagens com aditivos tiveram a concentracao de acido lactico diminuida significativamente no intervalo para o dia 56 e, com excecao do M734, foram menores que a silagem T, chegando a não ser detectado acido lactico nas silagens do Rumbosol 91 tratados com U, CC, e UCC. Somente as silagens com U*CC foram consistentes em alterar os teores de acido butirico no dia 56 para todos os genotipos (3,62%; 2,73% e 1,69% para o V2000, Rumbosol 91 e M734, respectivamente). O uso do CC elevou a concentracao de acido propionico para 1,39% no ultimo dia de abertura no Rumbosol 91. Sua associacao com ureia resultou em aumento do teor de acido propionico nas silagens do V2000 (0,84%) e do Rumbosol 91 (1,32%). Os aditivos utilizados neste experimentos nao promoveram melhores quanto aos teores dos acidos organicos analisados nas silagens de girassol