Distance from a fishing community explains fish abundance in a no-take zone with weak compliance

There are numerous examples of no-take marine reserves effectively conserving fish stocks within their boundaries. However, no-take reserves can be rendered ineffective and turned into ‘paper parks’ through poor compliance and weak enforcement of reserve regulations. Long-term monitoring is thus essential to assess the effectiveness of marine reserves in meeting conservation and management objectives. This study documents the present state of the 15-year old no-take zone (NTZ) of South El Ghargana within the Nabq Managed Resource Protected Area, South Sinai, Egyptian Red Sea. Previous studies credited willing compliance by the local fishing community for the increased abundances of targeted fish within the designated NTZ boundaries compared to adjacent fished or take-zones. We compared benthic habitat and fish abundance within the NTZ and the adjacent take sites open to fishing, but found no significant effect of the reserve. Instead, the strongest evidence was for a simple negative relationship between fishing pressure and distance from the closest fishing village. The abundance of targeted piscivorous fish increased significantly with increasing distance from the village, while herbivorous fish showed the opposite trend. This gradient was supported by a corresponding negative correlation between the amount of discarded fishing gear observed on the reef and increasing distance from the village. Discarded fishing gear within the NTZ suggested decreased compliance with the no-take regulations. Our findings indicate that due to non-compliance the no-take reserve is no longer functioning effectively, despite its apparent initial successes and instead a gradient of fishing pressure exists with distance from the nearest fishing community

Speech Communication

Contains reports on five research projects.U. S. Air Force (Electronic Systems Division) under Contract AF 19(628)-3325National Science Foundation (Grant GP-Z495)National Institutes of Health (Grant MH-04737-04)National Institutes of Health (Grant NB-0433Z-02)National Aeronautics and Space Administration (Grant NsG-496

Simulation and validation of injection-compression filling stage of liquid moulding with fast curing resins

Very short manufacture cycle times are required if continuous carbon fibre and epoxy composite components are to be economically viable solutions for high volume composite production for the automotive industry. Here, a manufacturing process variant of resin transfer moulding (RTM), targets a reduction of in-mould manufacture time by reducing the time to inject and cure components. The process involves two stages; resin injection followed by compression. A flow simulation methodology using an RTM solver for the process has been developed. This paper compares the simulation prediction to experiments performed using industrial equipment. The issues encountered during the manufacturing are included in the simulation and their sensitivity to the process is explored

Anti-tubulin drugs conjugated to anti-ErbB antibodies selectively radiosensitize.

Tumour resistance to radiotherapy remains a barrier to improving cancer patient outcomes. To overcome radioresistance, certain drugs have been found to sensitize cells to ionizing radiation (IR). In theory, more potent radiosensitizing drugs should increase tumour kill and improve patient outcomes. In practice, clinical utility of potent radiosensitizing drugs is curtailed by off-target side effects. Here we report potent anti-tubulin drugs conjugated to anti-ErbB antibodies selectively radiosensitize to tumours based on surface receptor expression. While two classes of potent anti-tubulins, auristatins and maytansinoids, indiscriminately radiosensitize tumour cells, conjugating these potent anti-tubulins to anti-ErbB antibodies restrict their radiosensitizing capacity. Of translational significance, we report that a clinically used maytansinoid ADC, ado-trastuzumab emtansine (T-DM1), with IR prolongs tumour control in target expressing HER2+ tumours but not target negative tumours. In contrast to ErbB signal inhibition, our findings establish an alternative therapeutic paradigm for ErbB-based radiosensitization using antibodies to restrict radiosensitizer delivery

The Prevalence of Skin Diseases and Its Association with Hygiene Behavior and Level of Education in a Pesantren, Jakarta Selatan 2013

Skin diseases are very common in places where the society lives in a crowded area. Pesantren is anIslamic school with a dormitory for its students, thus making the spread of skin infection easier to occur. Theobjective of this research was to identify the association between the prevalence of skin diseases with the hygienebehavior and level of education of santris (students of pesantren). This cross-sectional study was conducted in apesantren in South Jakarta. Data collection was carried out through a questionnaire consisting of ten questionsabout hygienic behaviors and history of previous dermatological examinations from July until September 2013.Results showed that out of 98 santris, 88 of them had skin diseases (89.7%). The most frequent skin infectionwas scabies with 67 cases (49.3%). Furthermore, 78 (88.6%) out of all santris who had skin diseases, werecategorized to have poor hygienic behaviors. There were only 10 santris that did not have any skin disease, 3of them had good hygienic behaviors. There was no significant difference between hygienic behaviors of santrisand the prevalence of skin disease (p=0.350). Associated with the level of education, ibtidaiyah had the highestnumber of santris (51.2%) affected by skin diseases. There was a significant difference between the level ofeducation and the prevalence of skin diseases (p<0.001). In coclusion, the prevalence of skin diseases in thepesantren was 89.7%; there was no association between skin diseases and hygienic behaviors. However, therewas an association between skin diseases and level of education

Evaluation of preferences of women and healthcare professionals in Singapore for implementation of noninvasive prenatal testing for Down syndrome

INTRODUCTION: Invasive prenatal diagnosis (IPD) has long been used to prenatally diagnose Down syndrome (DS), but is associated with a small risk of miscarriage. Meanwhile, noninvasive prenatal testing (NIPT) is a highly sensitive screening test using cell-free DNA in maternal blood for detection of DS that removes the risk of miscarriage, but confers a small risk of false-positive and false-negative results. Their implementations into clinical practice require an understanding of stakeholder preferences. METHODS: A total of 69 health professionals (HPs) and 301 women took part in a discrete choice experiment (DCE) in which preferences for four prenatal test attributes (accuracy, time of results, risk of miscarriage and amount of information provided) were assessed, and conditional logit regression was used to analyse data. Data on demographics and ranked preferences for test attributes were collected, and a direct choice between NIPT, IPD or neither test was given. RESULTS: Women showed a preference for test safety, whereas HPs prioritised test accuracy above all other attributes. When offered a direct choice between NIPT, IPD or neither test, women aged over 35 years, those with previous miscarriage or who knew a child with DS were more likely to choose NIPT than IPD. Chinese women preferred NIPT whereas Indian women preferred IPD. CONCLUSION: Our data highlight the need for patient-specific counselling, taking into account previous experiences and cultural factors. Since women and HPs prioritise different test attributes, it is essential that HPs recognise these differences in order to provide non-biased counselling

Identification of Bruton's tyrosine kinase as a therapeutic target in acute myeloid leukemia

Bruton's tyrosine kinase (BTK) is a cytoplasmic protein found in all hematopoietic cell lineages except for T cells. BTK mediates signalling downstream of a number of receptors. Pharmacological targeting of BTK using ibrutinib (previously PCI-32765) has recently shown encouraging clinical activity in a range of lymphoid malignancies. This study reports for the first time that ibrutinib inhibits blast proliferation from human acute myeloid leukaemia (AML) and that treatment with ibrutinib significantly augmented cytotoxic activities of standard AML chemotherapy cytarabine or daunorubicin. Here we describe that BTK is constitutively phosphorylated in the majority of AML samples tested, with BTK phosphorylation correlating highly with the cell's cytotoxic sensitivity towards ibrutinib. BTK targeted RNAi knock-down reduced colony forming capacity of primary AML blasts and proliferation of AML cell lines. We showed ibrutinib binds at nanomolar range to BTK. Furthermore, we also showed ibrutinib's anti-proliferative effects in AML are mediated via an inhibitory effect on downstream nuclear factor-κB (NF-κB) survival pathways. Moreover, ibrutinib inhibited AML cell adhesion to bone marrow stroma. Furthermore, these effects of ibrutinib in AML were seen at comparable concentrations efficacious in chronic lymphocytic leukemia (CLL). These results provide a biologic rationale for clinical evaluation of BTK inhibition in AML patients

Kinase-independent role for CRAF-driving tumour radioresistance via CHK2

Although oncology therapy regimens commonly include radiation and genotoxic drugs, tumour cells typically develop resistance to these interventions. Here we report that treatment of tumours with ionizing radiation or genotoxic drugs drives p21-activated kinase 1 (PAK1)-mediated phosphorylation of CRAF on Serine 338 (pS338) triggering a kinase-independent mechanism of DNA repair and therapeutic resistance. CRAF pS338 recruits CHK2, a cell cycle checkpoint kinase involved in DNA repair, and promotes CHK2 phosphorylation/activation to enhance the tumour cell DNA damage response. Accordingly, a phospho-mimetic mutant of CRAF (S338D) is sufficient to induce the CRAF/CHK2 association enhancing tumour radioresistance, while an allosteric CRAF inhibitor sensitizes tumour cells to ionizing radiation or genotoxic drugs. Our findings establish a role for CRAF in the DNA damage response that is independent from its canonical function as a kinase

Retreatment with brentuximab vedotin in patients with CD30-positive hematologic malignancies

BACKGROUND: Brentuximab vedotin is a CD30-directed antibody-drug conjugate. Retreatment with brentuximab vedotin monotherapy was investigated in patients with CD30-positive Hodgkin lymphoma (HL) or systemic anaplastic large cell lymphoma (ALCL) who relapsed after achieving complete or partial remission (CR or PR) with initial brentuximab vedotin therapy in a previous study (ClinicalTrials.gov NCT00947856). METHODS: Twenty-one patients with HL and 8 patients with systemic ALCL were retreated; 3 patients with systemic ALCL were retreated twice. Patients generally received brentuximab vedotin 1.8 mg/kg intravenously approximately every 3 weeks over 30 minutes as an outpatient infusion. The primary objectives of this study were to assess safety and to estimate antitumor activity of brentuximab vedotin retreatment. RESULTS: The objective response rate was 60% (30% CR) in HL patients and 88% (63% CR) in systemic ALCL patients. The estimated median duration of response for patients with an objective response was 9.5 months (range, 0.0+ to 28.0+ months) at the time of study closure. Of the 19 patients with objective response, 7 patients had not had an event of disease progression or death at the time of study closure; duration of response for these patients ranged from 3.5 to 28 months. Of the 11 patients with CR, 45% had response durations of over 1 year. Adverse events (AEs) occurring in ≥25% of patients during the retreatment period were generally similar in type and frequency to those observed in the pivotal trials of brentuximab vedotin monotherapy, with the exception of peripheral neuropathy, which is known to have a cumulative effect. Grade 3 or higher events were observed in 48% of patients; these were generally transient and managed by dose modifications or delays. Deaths due to AEs occurred in 3 HL patients; none were considered to be related to brentuximab vedotin retreatment. DISCUSSION: With the exception of a higher rate of peripheral motor neuropathy, retreatment with brentuximab vedotin was associated with similar side effects seen in the pivotal trials. CONCLUSIONS: Retreatment with brentuximab vedotin monotherapy is associated with response rates in 68% (39% CR) of patients with relapsed HL and systemic ALCL. TRIAL REGISTRATION: United States registry and results database ClinicalTrials.gov NCT00947856