Dynamics of the Indonesian seas circulation. Part I – The influence of bottom topography on temperature and salinity distributions

The influence of bottom topography on the distribution of temperature and salinity in the Indonesian seas region has been studied with a high-resolution model based on the Princeton Ocean Model. One of the distinctive properties of the model is an adequate reproduction of all major topographic features in the region by the model bottom relief. The three major routes of flow of Pacific water through the region have been identified. The western route follows the flow of North Pacific Water through the Sulawesi Sea, Makassar Strait, Flores Sea, and Banda Sea. This is the main branch of the Indonesian Throughflow. The eastern routes follow the flow of South Pacific water through the eastern Indonesian seas. This water enters the region either through the Halmahera Sea or by flowing to the north around Halmahera Island into the Morotai Basin and then into the Maluku Sea. A deep southward flow of South Pacific Water fills the Seram Sea below 1200 m through the Lifamatola Passage. As it enters the Seram Sea, this overflow turns eastward at depths greater than 2000 m, then upwells in the eastern part of the Seram Sea before returning westward at ~1500-2000 m. The flow continues westward across the Seram Sea, spreading to greater depths before entering the Banda Sea at the Buru-Mangole passage. It is this water that shapes the temperature and salinity of the deep Banda Sea. Topographic elevations break the Indonesian seas region down into separate basins. The difference in the distributions of potential temperature, ?, and salinity, S, in adjacent basins is primarily due to specific properties of advection of ? and S across a topographic rise. By and large, the topographic rise blocks deep flow between basins whereas water shallower than the depth of the rise is free to flow between basins. To understand this process, the structure of simulated fields of temperature and salinity has been analyzed. To identify a range of advected ? or S, special sections over the sills with isotherms or isohalines and isotachs of normal velocity have been considered. Following this approach the impact of various topographic rises on the distribution of ? and S has been identified. There are no substantial structural changes of potential temperature and salinity distributions between seasons, though values of some parameters of temperature and salinity distributions, e.g., magnitudes of maxima and minima, can change. It is shown that the main structure of the observed distributions of temperature and salinity is satisfactorily reproduced by the model throughout the entire domain.

Hot-melt extrusion technology and pharmaceutical application

The use of hot-melt extrusion (HME) within the pharmaceutical industry is steadily increasing, due to its proven ability to efficiently manufacture novel products. The process has been utilized readily in the plastics industry for over a century and has been used to manufacture medical devices for several decades. The development of novel drugs with poor solubility and bioavailability brought the application of HME into the realm of drug-delivery systems. This has specifically been shown in the development of drug-delivery systems of both solid dosage forms and transdermal patches. HME involves the application of heat, pressure and agitation through an extrusion channel to mix materials together, and subsequently forcing them out through a die. Twin-screw extruders are most popular in solid dosage form development as it imparts both dispersive and distributive mixing. It blends materials while also imparting high shear to break-up particles and disperse them. HME extrusion has been shown to molecularly disperse poorly soluble drugs in a polymer carrier, increasing dissolution rates and bioavailability. The most common difficulty encountered in producing such dispersions is stabilization of amorphous drugs, which prevents them from recrystallization during storage. Pharmaceutical industrial suppliers, of both materials and equipment, have increased their development of equipment and chemicals for specific use with HME. Clearly, HME has been identified as an important and significant process to further enhance drug solubility and solid-dispersion production. © 2012 Future Science Ltd.

Conservation status and reproduction of the critically endangered freshwater pearl mussel (Margaritifera margaritifera).

1. Freshwater unionoids are one of the most threatened animal groups worldwide and the freshwater pearl mussel Margaritifera margaritifera is currently listed as critically endangered in Europe. The ‘EC Habitats & Species Directive’ requires that EU member states monitor the distribution and abundance of this species and report regularly on its conservation status.
2. The pearl mussel meta-population in Northern Ireland was surveyed to assess temporal population trends in Special Areas of Conservation (SACs) and mussel reproduction throughout its range.
3. Mussels occurred in six rivers and numbers within three SAC designated sites remained stable between 2004-07 and 2011. The discovery of >8,000 previously unknown individuals in the Owenreagh River contributed to an overall increase (+56.8%) in the total known population. All populations actively reproduced during 2010 with approximately half of all individuals gravid. Moreover, suitable salmonid hosts occurred at all sites with 10.7% of salmon and 22.8% of trout carrying encysted glochidia. Populations were composed entirely of aged individuals with little evidence of recent recruitment.
4. We infer that the break in the life cycle must occur during the juvenile stage when glochidia metamorphose and settle into the interstitial spaces within the substrate. Water quality parameters, most notably levels of suspended solids, exceeded the recommended maximum thresholds in all rivers.
5. We posit that the deposition of silt may be the main cause of juvenile mortality contributing to a lack of recruitment. Consequently, all populations were judged to be in ‘unfavourable’ conservation status. Catchment-level management plans are urgently needed to reduce siltation with the aim of improving recruitment. Our results have implications for the success of ex-situ conservation programmes; specifically, the size at which captive bred juveniles are released into the wild. Further research is required to assess the vulnerabilities of early life stages of M. margaritifera to siltation.

Force-induced activation of covalent bonds in mechanoresponsive polymeric materials

Mechanochemical transduction enables an extraordinary range of physiological processes such as the sense of touch, hearing, balance, muscle contraction, and the growth and remodelling of tissue and
bone1–6. Although biology is replete with materials systems that actively and functionally respond to mechanical stimuli, the default mechanochemical reaction of bulk polymers to large external stress is the unselective scission of covalent bonds, resulting in damage or failure7. An alternative to this degradation process is the rational molecular design of synthetic materials such that mechanical stress
favourably altersmaterial properties. A few mechanosensitive polymers with this property have been developed8–14; but their active response is mediated through non-covalent processes, which may
limit the extent to which properties can be modified and the longterm stability in structural materials. Previously, we have shown with dissolved polymer strands incorporating mechanically sensitive chemical groups—so-called mechanophores—that the directional nature of mechanical forces can selectively break and re-form covalent bonds15,16. We now demonstrate that such forceinduced covalent-bond activation can also be realized with mechanophore-linked elastomeric and glassy polymers, by using a mechanophore that changes colour as it undergoes a reversible electrocyclic ring-opening reaction under tensile stress and thus allows us to directly and locally visualize the mechanochemical reaction. We find that pronounced changes in colour and fluorescence emerge with the accumulation of plastic deformation, indicating that in these polymeric materials the transduction of mechanical force into the ring-opening reaction is an activated process. We anticipate that force activation of covalent bonds can serve as a general strategy for the development of new mechanophore building blocks that impart polymeric materials with desirable functionalities ranging from damage sensing to fully regenerative self-healing.

Super-Resolution without Evanescent Waves

The past decade has seen numerous efforts to achieve imaging resolution beyond that of the Abbe-Rayleigh diffraction limit. The main direction of research alining to break this limit seeks to exploit the evanescent components containing fine detail of the electromagnetic field distribution at the Immediate proximity of the object. Here, we propose a solution that removes the need for evanescent fields. The object being imaged or stimulated with subwavelangth accuracy does not need to be In the immediate proximity of the superlens or field concentrator: an optical mask can be designed that creates constructive Interference of waves known as superoscillation, leading to a subwavelength focus of prescribed size and shape in a field of view beyond the evanescent fields, when illuminated by a monochromatic wave. Moreover, we demonstrate that such a mask may be used not only as a focusing device but also as a super-resolution imaging device.

Interventions for prevention of giant retinal tear in the fellow eye

Background: A giant retinal tear is a full-thickness retinal break that extends circumferentially around the retina for 90 degrees ormore in the presence of a posteriorly detached vitreous. It causes significant visual morbidity from retinal detachment and proliferative vitreoretinopathy. The fellow eye of patients who have had a spontaneous giant retinal tear has an increased risk of developing a giant retinal tear, a retinal detachment or both. Interventions such as 360-degree encircling scleral buckling, 360-degree cryotherapy and 360-degree laser photocoagulation have been advocated by some ophthalmologists as prophylaxis for the fellow eye against the development of a giant retinal tear and/or a retinal detachment, or to prevent its extension. Objectives: To evaluate the effectiveness of prophylactic 360-degree interventions in the fellow eye of patients with unilateral giant retinal tear to prevent the occurrence of a giant retinal tear and/or a retinal detachment. Search strategy: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2008, Issue 4), MEDLINE (January 1950 to December 2008), EMBASE (January 1980 to December 2008) and Latin American and Caribbean Literature on Health Sciences (LILACS) (January 1982 to December 2008). In addition, we searched the proceedings of the Annual Meeting of the Association for Research in Vision and Ophthalmology (ARVO) up to 2008 for information about other relevant studies. There were no language or date restrictions in the search for trials. The electronic databases were last searched on 15 December 2008. Selection criteria: Prospective randomised controlled trials (RCTs) comparing one prophylactic treatment for fellow eyes of patients with giant retinal tear against observation (no treatment) or another form of prophylactic treatment. In the absence of RCTs, we planned to discuss case-control studies that met the inclusion criteria but we would not conduct a meta-analysis using these studies. Data collection and analysis: We did not find any studies that met the inclusion criteria for the review and therefore no assessment of methodological quality or meta-analysis could be performed. Main results: No studies met the inclusion criteria for this review. Authors' conclusions: No strong evidence in the literature was found to support or refute prophylactic 360-degree treatments to prevent a giant retinal tear or a retinal detachment in the fellow eye of patients with unilateral giant retinal tears. Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

Interventions for prevention of giant retinal tear in the fellow eye.

BACKGROUND: A giant retinal tear is a full-thickness retinal break that extends circumferentially around the retina for 90 degrees or more in the presence of a posteriorly detached vitreous. It causes significant visual morbidity from retinal detachment and proliferative vitreoretinopathy. The fellow eye of patients who have had a spontaneous giant retinal tear has an increased risk of developing a giant retinal tear, a retinal detachment or both. Interventions such as 360-degree encircling scleral buckling, 360-degree cryotherapy and 360-degree laser photocoagulation have been advocated by some ophthalmologists as prophylaxis for the fellow eye against the development of a giant retinal tear and/or a retinal detachment, or to prevent its extension. OBJECTIVES: To evaluate the effectiveness of prophylactic 360-degree interventions in the fellow eye of patients with unilateral giant retinal tear to prevent the occurrence of a giant retinal tear and/or a retinal detachment. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2008, Issue 4), MEDLINE (January 1950 to December 2008), EMBASE (January 1980 to December 2008) and Latin American and Caribbean Literature on Health Sciences (LILACS) (January 1982 to December 2008). In addition, we searched the proceedings of the Annual Meeting of the Association for Research in Vision and Ophthalmology (ARVO) up to 2008 for information about other relevant studies. There were no language or date restrictions in the search for trials. The electronic databases were last searched on 15 December 2008. SELECTION CRITERIA: Prospective randomised controlled trials (RCTs) comparing one prophylactic treatment for fellow eyes of patients with giant retinal tear against observation (no treatment) or another form of prophylactic treatment. In the absence of RCTs, we planned to discuss case-control studies that met the inclusion criteria but we would not conduct a meta-analysis using these studies. DATA COLLECTION AND ANALYSIS: We did not find any studies that met the inclusion criteria for the review and therefore no assessment of methodological quality or meta-analysis could be performed. MAIN RESULTS: No studies met the inclusion criteria for this review. AUTHORS' CONCLUSIONS: No strong evidence in the literature was found to support or refute prophylactic 360-degree treatments to prevent a giant retinal tear or a retinal detachment in the fellow eye of patients with unilateral giant retinal tears.

Interventions for prevention of giant retinal tear in the fellow eye.

A giant retinal tear is a full-thickness retinal break that extends circumferentially around the retina for 90 degrees or more in the presence of a posteriorly detached vitreous. It causes significant visual morbidity from retinal detachment and proliferative vitreoretinopathy. The fellow eye of patients who have had a spontaneous giant retinal tear has an increased risk of developing a giant retinal tear, a retinal detachment or both. Interventions such as 360-degree encircling scleral buckling, 360-degree cryotherapy and 360-degree laser photocoagulation have been advocated by some ophthalmologists as prophylaxis for the fellow eye against the development of a giant retinal tear and/or a retinal detachment, or to prevent its extension. To evaluate the effectiveness of prophylactic 360-degree interventions in the fellow eye of patients with unilateral giant retinal tear to prevent the occurrence of a giant retinal tear, a retinal detachment or both. We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2011, Issue 11), MEDLINE (January 1950 to December 2011), EMBASE (January 1980 to December 2011), Latin American and Caribbean Literature on Health Sciences (LILACS) (January 1982 to December 2011), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov) and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). There were no date or language restrictions in the electronic searches for trials. The electronic databases were last searched on 6 December 2011. In addition, we searched the proceedings of the Annual Meeting of the Association for Research in Vision and Ophthalmology (ARVO) up to 2008 for information about other relevant studies. Prospective randomised controlled trials (RCTs) comparing one prophylactic treatment for fellow eyes of patients with giant retinal tear against observation (no treatment) or another form of prophylactic treatment. In the absence of RCTs, we planned to discuss case-control studies that met the inclusion criteria but we would not conduct a meta-analysis using these studies. We did not find any studies that met the inclusion criteria for the review and therefore no assessment of methodological quality or meta-analysis could be performed. No studies met the inclusion criteria for this review. No strong evidence in the literature was found to support or refute prophylactic 360-degree treatments to prevent a giant retinal tear or a retinal detachment in the fellow eye of patients with unilateral giant retinal tears.

Targeting EGFR Induced Oxidative Stress by PARP1 Inhibition in Glioblastoma Therapy

Despite the critical role of Epidermal Growth Factor Receptor (EGFR) in glioblastoma pathogenesis [1,2], EGFR targeted therapies have achieved limited clinical efficacy [3]. Here we propose an alternate therapeutic strategy based on the conceptual framework of non-oncogene addiction [4,5]. A directed RNAi screen revealed that glioblastoma cells overexpressing EGFRvIII [6], an oncogenic variant of EGFR, become hyper-dependent on a variety of DNA repair genes. Among these, there was an enrichment of Base Excision Repair (BER) genes required for the repair of Reactive Oxygen Species (ROS)-induced DNA damage, including poly-ADP ribose polymerase 1 (PARP1). Subsequent studies revealed that EGFRvIII overexpression in glioblastoma cells caused increased levels of ROS, DNA strand break accumulation, and genome instability. In a panel of primary glioblastoma lines, sensitivity to PARP1 inhibition correlated with the levels of EGFR activation and oxidative stress. Gene expression analysis indicated that reduced expression of BER genes in glioblastomas with high EGFR expression correlated with improved patient survival. These observations suggest that oxidative stress secondary to EGFR hyperactivation necessitates increased cellular reliance on PARP1 mediated BER, and offer critical insights into clinical trial design.

Laser peripheral iridoplasty for angle-closure

BACKGROUND: Angle-closure glaucoma is a leading cause of irreversible blindness in the world. Treatment is aimed at opening the anterior chamber angle and lowering the IOP with medical and/or surgical treatment (e.g. trabeculectomy, lens extraction). Laser iridotomy works by eliminating pupillary block and widens the anterior chamber angle in the majority of patients. When laser iridotomy fails to open the anterior chamber angle, laser iridoplasty may be recommended as one of the options in current standard treatment for angle-closure. Laser peripheral iridoplasty works by shrinking and pulling the peripheral iris tissue away from the trabecular meshwork. Laser peripheral iridoplasty can be used for crisis of acute angle-closure and also in non-acute situations.

OBJECTIVES: To assess the effectiveness of laser peripheral iridoplasty in the treatment of narrow angles (i.e. primary angle-closure suspect), primary angle-closure (PAC) or primary angle-closure glaucoma (PACG) in non-acute situations when compared with any other intervention. In this review, angle-closure will refer to patients with narrow angles (PACs), PAC and PACG.

SEARCH METHODS: We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2011, Issue 12), MEDLINE (January 1950 to January 2012), EMBASE (January 1980 to January 2012), Latin American and Caribbean Literature on Health Sciences (LILACS) (January 1982 to January 2012), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov) and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). There were no date or language restrictions in the electronic searches for trials. The electronic databases were last searched on 5 January 2012.

SELECTION CRITERIA: We included only randomised controlled trials (RCTs) in this review. Patients with narrow angles, PAC or PACG were eligible. We excluded studies that included only patients with acute presentations, using laser peripheral iridoplasty to break acute crisis.

DATA COLLECTION AND ANALYSIS: No analysis was carried out as only one trial was included in the review.

MAIN RESULTS: We included one RCT with 158 participants. The trial reported laser peripheral iridoplasty as an adjunct to laser peripheral iridotomy compared to iridotomy alone. The authors report no superiority in using iridoplasty as an adjunct to iridotomy for IOP, number of medications or need for surgery.

AUTHORS' CONCLUSIONS: There is currently no strong evidence for laser peripheral iridoplasty's use in treating angle-closure.

Laser peripheral iridoplasty for angle-closure

BACKGROUND: Angle-closure glaucoma is a leading cause of irreversible blindness in the world. Treatment is aimed at opening the anterior chamber angle and lowering the IOP with medical and/or surgical treatment (e.g. trabeculectomy, lens extraction). Laser iridotomy works by eliminating pupillary block and widens the anterior chamber angle in the majority of patients. When laser iridotomy fails to open the anterior chamber angle, laser iridoplasty may be recommended as one of the options in current standard treatment for angle-closure. Laser peripheral iridoplasty works by shrinking and pulling the peripheral iris tissue away from the trabecular meshwork. Laser peripheral iridoplasty can be used for crisis of acute angle-closure and also in non-acute situations. OBJECTIVES: To assess the effectiveness of laser peripheral iridoplasty in the treatment of narrow angles (i.e. primary angle-closure suspect), primary angle-closure (PAC) or primary angle-closure glaucoma (PACG) in non-acute situations when compared with any other intervention. In this review, angle-closure will refer to patients with narrow angles, PAC and PACG. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library), MEDLINE, EMBASE and LILACS (Latin American and Caribbean Literature on Health Sciences). The databases were last searched on 11 February 2008. SELECTION CRITERIA: Only randomised controlled trials (RCTs) were eligible for inclusion in this review. Patients with narrow angles, PAC or PACG were eligible. Studies that included only patients with acute presentations, using laser peripheral iridoplasty to break acute crisis were excluded. DATA COLLECTION AND ANALYSIS: No analysis was carried out due to lack of trials. MAIN RESULTS: There were no RCTs assessing laser peripheral iridoplasty in the non-acute setting of angle-closure. AUTHORS' CONCLUSIONS: There is currently no strong evidence for laser peripheral iridoplasty's use in treating angle-closure.

Examining the presence of Arching-Action in Edge Stiffened Bridge Deck Cantilever Overhangs Subjected to a Wheel Load

Engineers have proposed the idea that there may be some arching action present in bridge deck cantilever overhangs stiffened along their longitudinal free edge, via a traffic barrier, subjected to a wheel load. This paper includes the details of a full-scale corrosion-free bridge deck with cantilever overhangs stiffened along their longitudinal free edge by a traffic barrier wall that has been constructed and tested under static and fatigue wheel loads at the University of Manitoba. It also reviews experimental test results and postulates various discussions that suggest the presence of arching-action in cantilever slab overhangs. Test results indicated static ultimate load capacities significantly greater than the ultimate capacity if the mode of failure and behavior of the cantilever overhang was completely flexural. These early results confirm and indicate the presence of arching-action resulting in a significant break-through in cantilever behavior when subjected to a wheel load. The theory to account for this arching-action is not yet developed and further research should be conducted.

Th1 not Th17 cells drive spontaneous MS-like disease despite a functional regulatory T cell response

Multiple sclerosis is considered a disease of complex autoimmune etiology, yet there remains a lack of consensus as to specific immune effector mechanisms. Recent analyses of experimental autoimmune encephalomyelitis, the common mouse model of multiple sclerosis, have investigated the relative contribution of Th1 and Th17 CD4 T cell subsets to initial autoimmune central nervous system (CNS) damage. However, inherent in these studies are biases influenced by the adjuvant and toxin needed to break self-tolerance. We investigated spontaneous CNS disease in a clinically relevant, humanized, T cell receptor transgenic mouse model. Mice develop spontaneous, ascending paralysis, allowing unbiased characterization of T cell immunity in an HLA-DR15-restricted T cell repertoire. Analysis of naturally progressing disease shows that IFN?(+) cells dominate disease initiation with IL-17(+) cells apparent in affected tissue only once disease is established. Tregs accumulate in the CNS but are ultimately ineffective at halting disease progression. However, ablation of Tregs causes profound acceleration of disease, with uncontrolled infiltration of lymphocytes into the CNS. This synchronous, severe disease allows characterization of the responses that are deregulated in exacerbated disease: the correlation is with increased CNS CD4 and CD8 IFN? responses. Recovery of the ablated Treg population halts ongoing disease progression and Tregs extracted from the central nervous system at peak disease are functionally competent to regulate myelin specific T cell responses. Thus, in a clinically relevant mouse model of MS, initial disease is IFN? driven and the enhanced central nervous system responses unleashed through Treg ablation comprise IFN? cytokine production by CD4 and CD8 cells, but not IL-17 responses.

Giant retinal tears

A giant retinal tear (GRT) is a full-thickness neurosensory retinal break that extends circumferentially around the retina for three or more clock hours in the presence of a posteriorly detached vitreous. Its incidence in large population-based studies has been estimated as 1.5% of rhegmatogenous retinal detachments, with a significant male preponderance, and bilaterality in 12.8%. Most GRTs are idiopathic, with trauma, hereditary vitreoretinopathies and high myopia each being causative in decreasing frequency. The vast majority of GRTs are currently managed with a pars plana vitrectomy; the use of adjunctive circumferential scleral buckling is debated, but no studies have shown a clear anatomical or visual advantage with its use. Similarly, silicone oil tamponade does not influence long-term outcomes when compared with gas. Primary and final retinal reattachment rates are achieved in 88% and 95% of patients, respectively. Even when the retina remains attached, however, visual recovery may be limited. Furthermore, fellow eyes of patients with a GRT are at higher risk of developing retinal tears and retinal detachment. Prophylactic treatment under these circumstances may be considered but there is no firm evidence of its efficacy at the present time.

Politically sensitive encounters: Ethnography, access and the benefits of ‘hanging out’

Negotiating politically sensitive research environments requires both a careful consideration of the methods involved, and a great deal of personal resolve. In drawing upon two distinct yet comparable fieldwork experiences this paper champions the benefits of ethnographic methods in seeking to gain positionality and research legitimacy amongst those identified as future research participants. The authors explore and discuss their use of the ethnographic concept of ‘hanging out’ in politically sensitive environments when seeking to negotiate access to potentially hard to reach participants living in challenging research environments. Through an illustrative examination of their experiences in researching commemorative rituals in Palestine and mental health in a Northern Irish prison, both authors reflect upon their use of hanging out when seeking to break down barriers and gain acceptance amongst their target research participants. Their involvement in a range of activities, not directly related to the overall aims of the research project, highlight a need for qualitative researchers to adopt a flexible research design, one that embraces serendipitous or chance encounters, when seeking to gain access to hard to reach research participants or when issues of researcher legitimacy are particularly pronounced such as is the case in politically sensitive research environments.