You and Your Neighbor

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Bat3 deficiency accelerates the degradation of Hsp70-2/HspA2 during spermatogenesis

Meiosis is critical for sexual reproduction. During meiosis, the dynamics and integrity of homologous chromosomes are tightly regulated. The genetic and molecular mechanisms governing these processes in vivo, however, remain largely unknown. In this study, we demonstrate that Bat3/Scythe is essential for survival and maintenance of male germ cells (GCs). Targeted inactivation of Bat3/Scythe in mice results in widespread apoptosis of meiotic male GCs and complete male infertility. Pachytene spermatocytes exhibit abnormal assembly and disassembly of synaptonemal complexes as demonstrated by abnormal SYCP3 staining and sustained γ-H2AX and Rad51/replication protein A foci. Further investigation revealed that a testis-specific protein, Hsp70-2/HspA2, is absent in Bat3-deficient male GCs at any stage of spermatogenesis; however, Hsp70-2 transcripts are expressed at normal levels. We found that Bat3 deficiency induces polyubiquitylation and subsequent degradation of Hsp70-2. Inhibition of proteasomal degradation restores Hsp70-2 protein levels. Our findings identify Bat3 as a critical regulator of Hsp70-2 in spermatogenesis, thereby providing a possible molecular target in idiopathic male infertility

The architectures of media power: editing, the newsroom, and urban public space

This paper considers the relation of the newsroom and the city as a lens into the more general relation of production spaces and mediated publics. Leading theoretically from Lee and LiPuma’s (2002) notion of ‘cultures of circulation’, and drawing on an ethnography of the Toronto Star, the paper focuses on how media forms circulate and are enacted through particular practices and material settings. With its attention to the urban milieus and orientations of media organizations, this paper exhibits both affinities with but also differences to current interests in the urban architectures of media, which describe and theorize how media get ‘built into’ the urban experience more generally. In looking at editing practices situated in the newsroom, an emphasis is placed on the phenomenological appearance of media forms both as objects for material assembly as well as more abstracted subjects of reflexivity, anticipation and purposiveness. Although this is explored with detailed attention to the settings of the newsroom and the city, the paper seeks to also provide insight into the more general question of how publicness is material shaped and sited

Acute hepatic failure and multi-system organ failure secondary to replacement of the liver with metastatic melanoma

BACKGROUND: Metastatic malignant melanoma to the liver resulting in fulminant hepatic failure is a rare occurrence. CASE PRESENTATION: A 46 year old man presented to hospital with massive hepatomegaly, elevated liver enzymes and increased lactate three weeks following resection of a malignant melanoma from his shoulder (Clark level 5). Initially stable, he decompensated 24 to 48 hours subsequent to presentation with respiratory failure requiring mechanical ventilation, distributive shock requiring high dose vasopressor infusion, coagulopathy refractory to plasma infusion, progressive rise in liver enzymes and severe metabolic abnormalities including hyperkalemia, acidosis, hyperphosphatemia, hyperuricemia and hypocalcemia. Refractory to aggressive physiologic support he received palliation. Autopsy revealed >80% liver infiltration by metastatic malignant melanoma. CONCLUSION: We report a case of fulminant hepatic failure secondary to metastatic malignant melanoma infiltration of the liver

Feasibility and acceptability of a motivational interviewing breastfeeding peer support intervention

An uncontrolled study with process evaluation was conducted in three U.K. community maternity sites to establish the feasibility and acceptability of delivering a novel breastfeeding peer-support intervention informed by motivational interviewing (MI; Mam-Kind). Peer-supporters were trained to deliver the Mam-Kind intervention that provided intensive one-to-one peer-support, including (a) antenatal contact, (b) face-to-face contact within 48 hr of birth, (c) proactive (peer-supporter led) alternate day contact for 2 weeks after birth, and (d) mother-led contact for a further 6 weeks. Peer-supporters completed structured diaries and audio-recorded face-to-face sessions with mothers. Semistructured interviews were conducted with a purposive sample of mothers, health professionals, and all peer-supporters. Interview data were analysed thematically to assess intervention acceptability. Audio-recorded peer-support sessions were assessed for intervention fidelity and the use of MI techniques, using the MITI 4.2 tool. Eight peer-supporters delivered the Mam-Kind intervention to 70 mothers in three National Health Service maternity services. Qualitative interviews with mothers (n = 28), peer-supporters (n = 8), and health professionals (n = 12) indicated that the intervention was acceptable, and health professionals felt it could be integrated with existing services. There was high fidelity to intervention content; 93% of intervention objectives were met during sessions. However, peer-supporters reported difficulties in adapting from an expert-by-experience role to a collaborative role. We have established the feasibility and acceptability of providing breastfeeding peer-support using a MI-informed approach. Refinement of the intervention is needed to further develop peer-supporters' skills in providing mother-centred support. The refined intervention should be tested for effectiveness in a randomised controlled trial

Fairy tale tourism: the architectural projection mapping of magically real and irreal festival lightscapes

This paper explores how established light festivals such as the Fête des Lumières in Lyon and Lumiere in Durham were first conceived by Robert-Houdin as illusory illuminations in the Loire in the 1950s. The research investigates the concept of spectacles as inversions of reality; re-situating light works within authenticity theory by exploring their manipulation of magical reality and irreality. The research uses the authors’ experience of event design to assess different interactions of light with the tri-dimensional architectural canvas, suggesting three classifications of animated projection mapping events: architecturally passive, architecturally physically active and architecturally metaphysically active. Each category has implications for how spectators perceive these installations. Architecturally passive events may use fairy tale content, evoking atavistic and affective responses, the ‘skinning’ of buildings with magical reality is designed to evoke perceptual duality, and the wobbling unfolding of irreality may ultimately create a state of ‘illuminated flow.

Sustainability of biosimilars in europe: A delphi panel consensus with systematic literature review

Introduction: Biosimilars have the potential to enhance the sustainability of evolving health care systems. A sustainable biosimilars market requires all stakeholders to balance competition and supply chain security. However, there is significant variation in the policies for pricing, procurement, and use of biosimilars in the European Union. A modified Delphi process was conducted to achieve expert consensus on biosimilar market sustainability in Europe. Methods: The priorities of 11 stakeholders were explored in three stages: a brainstorming stage supported by a systematic literature review (SLR) and key materials identified by the participants; development and review of statements derived during brainstorming; and a facilitated roundtable discussion. Results: Participants argued that a sustainable biosimilar market must deliver tangible and transparent benefits to the health care system, while meeting the needs of all stakeholders. Key drivers of biosimilar market sustainability included: (i) competition is more effective than regulation; (ii) there should be incentives to ensure industry investment in biosimilar development and innovation; (iii) procurement processes must avoid monopolies and minimize market disruption; and (iv) principles for procurement should be defined by all stakeholders. However, findings from the SLR were limited, with significant gaps on the impact of different tender models on supply risks, savings, and sustainability. Conclusions: A sustainable biosimilar market means that all stakeholders benefit from appropriate and reliable access to biological therapies. Failure to care for biosimilar market sustainability may impoverish biosimilar development and offerings, eventually leading to increased cost for health care systems and patients, with fewer resources for innovation

Liquid networks and the metaphysics of flux: ontologies of flow in an age of speed and mobility

It is common for social theorists to utilize the metaphors of ‘flow’, ‘fluidity’, and ‘liquidity’ in order to substantiate the ways in which speed and mobility form the basis for a new kind of information or network society. Yet rarely have these concepts been sufficiently theorized in order to establish their relevance or appropriateness. This article contends that the notion of flow as utilized in social theory is profoundly metaphysical in nature, and needs to be judged as such. Beginning with a discussion of the accelerating timescape that characterizes the network society, it will then move on to examine three main issues with this ‘metaphysics of flux’. First, that the concept of flows unjustly privileges the process of becoming and, as a result, is unable to account for the materiality, substantiality, and agency of the objects being mobilized, and the contingency of their mediation. Second, that it posits the accelerating tendencies of capital as an ontological inevitability, thus discounting resistance to such forces. Finally, that it ignores the human faculty for reason and speculative thought in developing alternative means of political praxis. The solution, it will be argued, is not to abandon metaphysical accounts of the network society, but rather to challenge those accounts that, in exhibiting a crude empiricism, work to justify the status quo