Interview with Professor Mark Brodin about his book "William P. Homans Jr.: A Life In Court"

Boston lawyer William P. Homans Jr. devoted his fifty-year career to the defense of the poor and downtrodden, the protection of our most basic civil liberties, and the abolition of the death penalty. Descendant of two of Boston's oldest and most prominent families, and combat veteran of both the British and American Navies during World War II, Homans became unlikely guru to the 1960s generation of radical lawyers and antiwar activists. He was on the defense team in the 1968 conspiracy trial of Dr. Benjamin Spock and four other leading opponents of the Vietnam War accused of aiding and abetting resistance to the military draft, and represented Dr. Kenneth Edelin in the 1975 manslaughter prosecution arising out of a lawful abortion performed after Roe v. Wade. The narrative contrasts Bill Homans' storied legal career with a troubled personal life in a balanced but unvarnished manner, testifying to the strength of the human spirit when committed to the pursuit of the common good. About the author: Mark S. Brodin is Professor of Law at Boston College Law School and the author of numerous books and law journal articles in the areas of civil and criminal procedure, evidence, litigation, and employment discrimination. A graduate of Columbia College (1969) and Columbia Law School (1972), he served as law clerk to United States District Judge Joseph L. Tauro and staff attorney with the Lawyers' Committee for Civil Rights in Boston. He has also practiced for brief periods as a public defender in Boston and a prosecutor in Norfolk County.

A "Trojan horse" strategy to reverse drug-resistance in brain tumors

Los gliomas malignos representan una de las formas más agresivas de los tumores del sistema nervioso central (SNC). De acuerdo con la clasificación de los tumores cerebrales de la Organización Mundial de la Salud (OMS), los astrocitomas han sido categorizados en cuatro grados, determinados por la patología subyacente. Es así como los gliomas malignos (o de alto grado) incluyen el glioma anaplásico (grado III) así como el glioblastoma multiforme (GBM, grado IV),estos últimos los más agresivos con el peor pronóstico (1). El manejo terapéutico de los tumores del SNC se basa en la cirugía, la radioterapia y la quimioterapia, dependiendo de las características del tumor, el estadio clínico y la edad (2),(3), sin embargo ninguno de los tratamientos estándar es completamente seguro y compatible con una calidad de vida aceptable (3), (4). En general, la quimioterapia es la primera opción en los tumores diseminados, como el glioblastoma invasivo y el meduloblastoma de alto riesgo o con metástasis múltiple, pero el pronóstico en estos pacientes es muy pobre (2),(3). Solamente nuevas terapias dirigidas (2) como las terapias anti-angiogénicas (4); o terapias génicas muestran un beneficio real en grupos limitados de pacientes con defectos moleculares específicos conocidos (4). De este modo, se hace necesario el desarrollo de nuevas terapias farmacológicas para atacar los tumores cerebrales. Frente a las terapias los gliomas malignos son con frecuencia quimioresistentes, y esta resistencia parece depender de al menos dos mecanismos: en primer lugar, la pobre penetración de muchas drogas anticáncer a través de la barrera hematoencefálica (BBB: Blood Brain Barrier), la barrera del fluido sangre-cerebroespinal (BCSFB: Blood-cerebrospinal fluid barrier) y la barrera sangre-tumor (BTB: blood-tumor barrier). Dicha resistencia se debe a la interacción de la droga con varios transportadores o bombas de eflujo de droga ABC (ABC: ATP-binding cassette) que se sobre expresan en las células endoteliales o epiteliales de estas barreras. En segundo lugar, estos transportadores de eflujo de drogas ABC propios de las células tumorales confieren un fenotipo conocido como resistencia a multidrogas (MDR: multidrug resistance), el cual es característico de varios tumores sólidos. Este fenotipo también está presente en los tumores del SNC y su papel en gliomas es objeto de investigación (5). Por consiguiente el suministro de medicamentos a través de la BBB es uno de los problemas vitales en los tratamientos de terapia dirigida. Estudios recientes han demostrado que algunas moléculas pequeñas utilizadas en estas terapias son sustratos de la glicoproteína P (Pgp: P-gycoprotein), así como también de otras bombas de eflujo como las proteínas relacionadas con la resistencia a multidrogas (MRPs: multidrug resistance-related proteins (MRPs) o la proteína relacionada con cáncer de seno (BCRP: breast-cancer resistance related protein)) que no permiten que las drogas de este tipo alcancen el tumor (1). Un sustrato de Pgp y BCRP es la DOXOrubicina (DOXO), un fármaco utilizado en la terapia anti cáncer, el cual es muy eficaz para atacar las células del tumor cerebral in vitro, pero con un uso clínico limitado por la poca entrega a través de la barrera hematoencefálica (BBB) y por la resistencia propia de los tumores. Por otra parte las células de BBB y las células del tumor cerebral tienen también proteínas superficiales, como el receptor de la lipoproteína de baja densidad (LDLR), que podría utilizarse como blanco terapéutico en BBB y tumores cerebrales. Es asi como la importancia de este estudio se basa en la generación de estrategias terapéuticas que promuevan el paso de las drogas a través de la barrera hematoencefalica y tumoral, y a su vez, se reconozcan mecanismos celulares que induzcan el incremento en la expresión de los transportadores ABC, de manera que puedan ser utilizados como blancos terapéuticos.Este estudio demostró que el uso de una nueva estrategia basada en el “Caballo de Troya”, donde se combina la droga DOXOrubicina, la cual es introducida dentro de un liposoma, salvaguarda la droga de manera que se evita su reconocimiento por parte de los transportadores ABC tanto de la BBB como de las células del tumor. La construcción del liposoma permitió utilizar el receptor LDLR de las células asegurando la entrada a través de la BBB y hacia las células tumorales a través de un proceso de endocitosis. Este mecanismo fue asociado al uso de estatinas o drogas anticolesterol las cuales favorecieron la expresión de LDLR y disminuyeron la actividad de los transportadores ABC por nitración de los mismos, incrementando la eficiencia de nuestro Caballo de Troya. Por consiguiente demostramos que el uso de una nueva estrategia o formulación denominada ApolipoDOXO más el uso de estatinas favorece la administración de fármacos a través de la BBB, venciendo la resistencia del tumor y reduciendo los efectos colaterales dosis dependiente de la DOXOrubicina. Además esta estrategia del "Caballo de Troya", es un nuevo enfoque terapéutico que puede ser considerado como una nueva estrategia para aumentar la eficacia de diferentes fármacos en varios tumores cerebrales y garantiza una alta eficiencia incluso en un medio hipóxico,característico de las células cancerosas, donde la expresión del transportador Pgp se vió aumentada. Teniendo en cuenta la relación entre algunas vías de señalización reconocidas como moduladores de la actividad de Pgp, este estudio presenta no solo la estrategia del Caballo de Troya, sino también otra propuesta terapéutica relacionada con el uso de Temozolomide más DOXOrubicina. Esta estrategia demostró que el temozolomide logra penetrar la BBB por que interviene en la via de señalización de la Wnt/GSK3/β-catenina, la cual modula la expresión del transportador Pgp. Se demostró que el TMZ disminuye la proteína y el mRNA de Wnt3 permitiendo plantear la hipótesis de que la droga al disminuir la transcripción del gen Wnt3 en células de BBB, incrementa la activación de la vía fosforilando la β-catenina y conduciendo a disminuir la β-catenina nuclear y por tanto su unión al promotor del gen mdr1. Con base en los resultados este estudio permitió el reconocimiento de tres mecanismos básicos relacionados con la expresión de los transportadores ABC y asociados a las estrategias empleadas: el primero fue el uso de las estatinas, el cual condujo a la nitración de los transportadores disminuyendo su actividad por la via del factor de transcripción NFκB; el segundo a partir del uso del temozolomide, el cual metila el gen de Wnt3 reduciendo la actividad de la via de señalización de la la β-catenina, disminuyendo la expresión del transportador Pgp. El tercero consistió en la determinación de la relación entre el eje RhoA/RhoA quinasa como un modulador de la via (no canónica) GSK3/β-catenina. Se demostró que la proteína quinasa RhoA promovió la activación de la proteína PTB1, la cual al fosforilar a GSK3 indujo la fosforilación de la β-catenina, lo cual dio lugar a su destrucción por el proteosoma, evitando su unión al promotor del gen mdr1 y por tanto reduciendo su expresión. En conclusión las estrategias propuestas en este trabajo incrementaron la citotoxicidad de las células tumorales al aumentar la permeabilidad no solo de la barrera hematoencefálica, sino también de la propia barrera tumoral. Igualmente, la estrategia del “Caballo de Troya” podría ser útil para la terapia de otras enfermedades asociadas al sistema nervioso central. Por otra parte estos estudios indican que el reconocimiento de mecanismos asociados a la expresión de los transportadores ABC podría constituir una herramienta clave en el desarrollo de nuevas terapias anticáncer.

Genotype and temperature influence pea aphid resistance to a fungal entomopathogen

The influence of temperature on life history traits of four Acyrthosiphon pisum clones was investigated, together with their resistance to one genotype of the fungal entomopathogen Erynia neoaphidis . There was no difference among aphid clones in development rate, but they did differ in fecundity. Both development rate and fecundity were influenced by temperature, but all clones showed similar responses to the changes in temperature (i.e. the interaction term was nonsignificant). However, there were significant differences among clones in susceptibility to the pathogen, and this was influenced by temperature. Furthermore, the clones differed in how temperature influenced susceptibility, with susceptibility rankings changing with temperature. Two clones showed changes in susceptibility which mirrored changes in the in vitro vegetative growth rate of E. neoaphidis at different temperatures, whereas two other clones differed considerably from this expected response. Such interactions between genotype and temperature may help maintain heritable variation in aphid susceptibility to fungal pathogen attack and have implications for our understanding of disease dynamics in natural populations. This study also highlights the difficulties of drawing conclusions about the efficacy of a biological control agent when only a restricted range of pest genotypes or environmental conditions are considered.

Influence of temperature on pea aphid Acyrthosiphon pisum (Hemiptera: Aphididae) resistance to natural enemy attack

The ability to resist or avoid natural enemy attack is a critically important insect life history trait, yet little is understood of how these traits may be affected by temperature. This study investigated how different genotypes of the pea aphid Acyrthosiphon pisum Harris, a pest of leguminous crops, varied in resistance to three different natural enemies (a fungal pathogen, two species of parasitoid wasp and a coccinellid beetle), and whether expression of resistance was influenced by temperature. Substantial clonal variation in resistance to the three natural enemies was found. Temperature influenced the number of aphids succumbing to the fungal pathogen Erynia neoaphidis Remaudiere & Hermebert, with resistance increasing at higher temperatures (18 vs. 28degreesC). A temperature difference of 5degreesC (18 vs. 23degreesC) did not affect the ability of A. pisum to resist attack by the parasitoids Aphidius ervi Haliday and A. eadyi Stary Gonzalez & Hall. Escape behaviour from foraging coccinellid beetles (Hippodamia convergens Guerin-Meneville) was not directly influenced by aphid clone or temperature (16 vs. 21degreesC). However, there were significant interactions between clone and temperature (while most clones did not respond to temperature, one was less likely to escape at 16degreesC), and between aphid clone and ladybird presence (some clones showed greater changes in escape behaviour in response to the presence of foraging coccinellids than others). Therefore, while larger temperature differences may alter interactions between Acyrthosiphon pisum and an entomopathogen, there is little evidence to suggest that smaller changes in temperature will alter pea aphid-natural enemy interactions.

Resistance, regard and rewriting: Virginia Woolf and Anne Thackeray Ritchie

This article discusses the literary relationship of the novelist and memoirist,Anne Thackeray Ritchie (1837–1919), and her step-niece, Virginia Woolf.Ritchie’s influence was a highly significant one which prompted a powerful ambiguity in Woolf, who was alternately admiring and dismissively anxious to deny influence, eager to relegate her to a staunchly Victorian past while covertly sensitive to those elements in her writing linking her with Modernism. These ‘Modern’ elements, including emphasis on the subjective nature of reality and the everyday life of the mind, occur in Ritchie’s fiction, affecting its style and structure. This article focuses on Night and Day, then on Woolf ’s more direct comments about Ritchie in diaries, letters and essays, comparing these comments and Woolf ’s theoretical agenda in defining Modernism and, implicitly, her own place in it. It also considers some of Ritchie’s fiction, with particular attention to two novellas, one a source for To The Lighthouse.

The commensal infant gut meta-mobilome as a potential reservoir for persistent multidrug resistance integrons

Despite the accumulating knowledge on the development and establishment of the gut microbiota, its role as a reservoir for multidrug resistance is not well understood. This study investigated the prevalence and persistence patterns of an integrase gene (int1), used as a proxy for integrons (which often carry multiple antimicrobial resistance genes), in the fecal microbiota of 147 mothers and their children sampled longitudinally from birth to 2 years. The study showed the int1 gene was detected in 15% of the study population, and apparently more persistent than the microbial community structure itself. We found int1 to be persistent throughout the first two years of life, as well as between mothers and their 2-year-old children. Metagenome sequencing revealed integrons in the gut meta-mobilome that were associated with plasmids and multidrug resistance. In conclusion, the persistent nature of integrons in the infant gut microbiota makes it a potential reservoir of mobile multidrug resistance.

Vigilant pleasure as autoethnography : the life of the tea mind as critical history

I examine tea as cultural practice by exploring how it is implicated in the formation of individual subjectivities and national identity. While using the experience of learning and consuming tea lore as a foreigner as my explicit point of entry, I analyse how tea transmission practices are represented in Japanese films. My readings of these films are supported by a survey of the historical applications of tea as part of a project of national invention. Against tea's self-representation as purely cultural, I draw attention to this ideological silencing of its economic and political effects by claiming that institutionalised tea pedagogy has been a major player in a nationally distinctive discourse of transience. My thesis argues that autoethnography can be used to bring into view the ideological foundations of various social practices organised around tea sites and texts. Once ideology is visible autoethnography may mediate the effects of dominant discourses by making a modest form of private resistance possible. As a performance of critical and effective history, I explore the limits of consciously resisting institutionalised power by reflecting on how discourses of tea and social theory intersect in my autoethnographic account of tea experiences. I begin by locating my subjectivity in tea. After outlining how tea is useful to me in psychological, domestic and professional contexts, I survey autoethnographic writing and critical forms of textual analysis. Given that traditions of textual analysis set limits to what can be comprehended, I note that considerations of the role of subjectivity are sometimes absent from several modes of textual analysis. I contend that more delicate forms of textual analysis are possible when multiple forms of subjectivity are explicitly addressed. Subjectivity is emphasised as I move between performances of being a cultural insider of tea subculture and an ethnic and linguistic outsider of daily life in Japan when I examine the connections linking tea anecdotes, film narratives, individual tales and national myths. From the position of tea culture insider and consumer of social theory I examine the relationship between national culture and individual subjectivity. I identify internal contradictions in tea transmission practices and consider how tea pedagogy and its cult of personality are addressed in tea films. The thesis concludes by considering the utility of identities in a global economy and comment on recent theories addressing the ethical self and social practices. It is on this basis that I claim the readings advanced in the earlier chapters map the pleasures and limits of employing autoethnography as a form of private resistance against the dominant discourses of tea, nation, and leisure.

Psychological responses to acute resistance exercise in men and women who are obese

The purpose of the study was to investigate the psychological response to the very first session of resistance exercise on positive well-being (PWB), psychological distress (PD), and perception of fatigue in untrained men and women who are obese. Forty-five (male = 22, female = 23) untrained, middle-aged volunteers (mean ± SEM, 51.0 ± 1.0; range, 40-69 years) participated in the study. Participants were divided into 4 groups according to sex and obesity level (i.e., men who are obese, men who are nonobese, women who are obese, women who are nonobese). The threshold for obesity was defined as waist circumference ≥94 cm for men and 80 cm for women. Measures included body composition, aerobic power, muscle strength, and quality of life (Short Form 36, SF-36). Before and after resistance exercise, participants completed the Subjective Exercise Experience Scale (SEES). Paired sample t-tests were used to assess changes in SEES scores within group pre- and post-exercise and repeated-measures analysis of variance were used to assess changes in SEES scores between groups. Exercise increased the perception of PWB in both women who are obese and nonobese, without changes in PD or fatigue. In women, the change in PWB after exercise was negatively correlated with most scales of the SF-36, particularly with the mental health dimension (r = -0.55, p < 0.01). No significant changes in PWB, PD, or fatigue were found in men who are obese. Acute resistance exercise improved PWB in women who are obese and nonobese and those with lower self-perceived quality of life scores at the start improved the most. In addition, resistance exercise did not increase feelings of distress in either women or men who are obese.

Osteo-cise : Strong bones for life': protocol for a community-based randomised controlled trial of a multi-modal exercise and osteoporosis education program for older adults at risk of falls and fractures

Background : Osteoporosis affects over 220 million people worldwide, and currently there is no 'cure' for the disease. Thus, there is a need to develop evidence-based, safe and acceptable prevention strategies at the population level that target multiple risk factors for fragility fractures to reduce the health and economic burden of the condition.

Methods : The 'Osteo-cise: Strong Bones for Life' study will investigate the effectiveness and feasibility of a multi-component targeted exercise, osteoporosis education/awareness and behavioural change program for improving bone health and muscle function, and reducing falls risk in community-dwelling older adults at an increased risk of fracture. Men and women aged 60 years or above will participate in an 18-month randomised controlled trial comprising a 12-month structured and supervised community-based program and a 6-month 'research to practise' translational phase. Participants will be randomly assigned to either the 'Osteo-cise' intervention or a self-management control group. The intervention will comprise a multi-modal exercise program incorporating high velocity progressive resistance training, moderate impact weight-bearing exercise and high challenging balance exercises performed three times weekly at local community-based fitness centres. A behavioural change program will be used to enhance exercise adoption and adherence to the program. Community-based osteoporosis education seminars will be conducted to improve participant knowledge and understanding of the risk factors and preventative measures for osteoporosis, falls and fractures. The primary outcomes measures, to be collected at baseline, 6, 12, and 18 months, will include DXA-derived hip and spine bone mineral density measurements and functional muscle power (timed stair-climb test). Secondary outcomes measures include: MRI-assessed distal femur and proximal tibia trabecular bone micro-architecture, lower limb and back maximal muscle strength, balance and function (four square step test, functional reach test, timed up-and-go test and 30-second sit-to-stand), falls incidence and health-related quality of life. Cost-effectiveness will also be assessed.

Discussion : The findings from the Osteo-cise: Strong Bones for Life study will provide new information on the efficacy of a targeted multi-modal community-based exercise program incorporating high velocity resistance training, together with an osteoporosis education and behavioural change program for improving multiple risk factors for falls and fracture in older adults at risk of fragility fracture. Trial Registration: Australian New Zealand Clinical Trials Registry reference ACTRN12609000100291

ICT to enhance the triangle of life : the soil, the seed, and the life-giver farmer

This paper reports on the outcomes of an ICT enabled social sustainability project “Green Lanka1” trialled in the Wilgamuwa village, which is situated in the Dambulla district of Sri Lanka. The main goals of the project were focused towards the provision of information about market prices, transportation options, agricultural decision support and modern agriculture practices of the farmer communities to improve their livelihood with the effective use of technologies. The project used Web and Mobile (SMS) enabled systems. The Green Lanka project was sponsored by the Information Communication Technology Agency (ICTA) of Sri Lanka under the Institutional Capacity Building Programme (ICBP) grant scheme which was sponsored by the World Bank. Six hundred families in Wilgamuwa village participated in the project activities. The project was designed, executed and studied through an Action Research approach. The lessons learned through the project activities provide an important understanding of the complex interaction between different stakeholders in the process of implementation of ICT enabled solutions within digitally divided societies. The paper analyses the processes used to reduce the resistance to change and improved involvement of farmer communities in ICT enabled projects. It also analyses the interaction between stakeholders involved in design and implementation of the project activities to improve the chances of project success.

Investigation of the plasmodium falciparum food vacuole through inducible expression of the chloroquine resistance transporter (PfCRT)

Haemoglobin degradation during the erythrocytic life stages is the major function of the food vacuole (FV) of Plasmodium falciparum and the target of several anti-malarial drugs that interfere with this metabolic pathway, killing the parasite. Two multi-spanning food vacuole membrane proteins are known, the multidrug resistance protein 1 (PfMDR1) and Chloroquine Resistance Transporter (PfCRT). Both modulate resistance to drugs that act in the food vacuole. To investigate the formation and behaviour of the food vacuole membrane we have generated inducible GFP fusions of chloroquine sensitive and resistant forms of the PfCRT protein. The inducible expression system allowed us to follow newly-induced fusion proteins, and corroborated a previous report of a direct trafficking route from the ER/Golgi to the food vacuole membrane. These parasites also allowed the definition of a food vacuole compartment in ring stage parasites well before haemozoin crystals were apparent, as well as the elucidation of secondary PfCRT-labelled compartments adjacent to the food vacuole in late stage parasites. We demonstrated that in addition to previously demonstrated Brefeldin A sensitivity, the trafficking of PfCRT is disrupted by Dynasore, a non competitive inhibitor of dynamin-mediated vesicle formation. Chloroquine sensitivity was not altered in parasites over-expressing chloroquine resistant or sensitive forms of the PfCRT fused to GFP, suggesting that the PfCRT does not mediate chloroquine transport as a GFP fusion protein.

The impact of an exercise physiologist coordinated resistance exercise program on the physical function of people receiving hemodialysis: a stepped wedge randomised control study

Background:

David Bowie: dancing with madness and proselytising the socio-political in art and life

A longstanding, successful and frequently controversial career spanning more than four decades establishes David Bowie as charged with individual agency. The notion of ‘agency’ here refers particularly to the ‘ability of people, individually and collectively to influence their own lives and the society in which they live’ (Germov and Poole, 2007: 7). That Bowie has influenced many lives is undeniable to his fans. He has long demonstrated an avid curiosity for the enduring patterns of social life which is reflected in his art. Bowie’s opus contains the elements of ideological narratives around sexual (mis)adventure, expressivity, and; resistance to ‘normative’ behaviour. He requisitions his audiences, through frequently indirect lyrics and images, to critically question sanity, identity and essentially what it means to be ‘us’ and why we are here. Here, in this context, ‘dancing with madness’ assumes an intimate relationship, even if brief, where ideas and emotions come passionately together for the purpose of creative expression much like the intertwining and energetic performance of the partner dance Tango. As such, ‘dancing’ is argued here to be an appropriate descriptor for how Bowie has engaged with creative cultural forms but not meant to be self-conscious nor indicate superficiality or ignorance. The idea of madness for its part is a theme in many of his compositions, for example the original album cover for The Man Who Sold the World (1971)  depicts an asylum and includes the song ‘All The Madmen’ and Aladdin Sane (1973)—a lad insane--are but two examples. This paper argues that Bowie’s frequently astute contemplations, manifest through his art over a period now spanning more than forty years, continues to draw fans of like mind to his work with the result that he has a legitimate claim to influence and affect.

Protein-enriched diet, with the use of lean red meat, combined with progressive resistance training enhances lean tissue mass and muscle strength and reduces circulating IL-6 concentrations in elderly women: a cluster randomized controlled trial.

Physical inactivity, inadequate dietary protein, and low-grade systemic inflammation contribute to age-related muscle loss, impaired function, and disability.

Acute resistance exercise increases the expression of chemotactic factors within skeletal muscle.

Intense resistance exercise causes mechanical loading of skeletal muscle, followed by muscle adaptation. Chemotactic factors likely play an important role in these processes.