Phase 2 Research Articles

The Response of the Southern Hemisphere Middle Atmosphere to the Madden–Julian Oscillation during Austral Winter Using the Specified-Dynamics Whole Atmosphere Community Climate Model

Abstract Using the specified-dynamics (SD) Whole Atmosphere Community Climate Model (SD-WACCM), the effects of the Madden–Julian oscillation (MJO) on the midwinter stratosphere and mesosphere in the Southern Hemisphere (SH) are investigated. The most significant responses of the SH polar cap temperature to the MJO are found about 30 days after MJO phase 1 (P1) and about 10 days after MJO phase 5 (P5) in both the ERA-Interim data and the SD-WACCM simulation. The 200- and 500-hPa geopotential height anomalies in the SH reveal that wave trains emanate from the Indian and Pacific Oceans when the MJO convection is enhanced in the eastern Indian Ocean and the western Pacific. As a result, the upward propagation and dissipation of planetary waves (PWs) in the middle and high latitudes of the SH stratosphere is significantly enhanced, the Brewer–Dobson (BD) circulation in the SH stratosphere strengthens, and temperatures in the SH polar stratosphere increase. Wavenumber 1 in the stratosphere is the dominant component of the PW perturbation induced by the MJO convection. In the SH mesosphere, the MJO leads to enhancement of the dissipation and breaking of gravity waves (GWs) propagating as a result of wind-filtering change in the SH extratropics and causes anomalous downwelling in the middle and high latitudes of the mesosphere. The circulation thus changes significantly, resulting in anomalous cooling in the mesosphere in response to MJO P1 and P5 at lags of 10 and 30 days, respectively.

The influence of composition and temperature on hydrated phase assemblages in magnesium oxychloride cements

AbstractDue to their nonhydraulic nature, magnesium oxychloride cements (MOCs) are susceptible to degradation following contact with water. Improving the water resistance of these materials requires better understanding of hydrated phase relations and the sensitivity of hydrated phases to water. Toward this end, a series of targeted experiments and complementary thermodynamic calculations were carried out to assess hydrated phase assemblages in the system MgO‐MgCl2‐H2O across a range of compositions. Focus is placed on appraising the effects of composition and reaction temperature. In broad agreement with literature data, under ambient conditions, hydrated MOCs are noted to contain Phase 3 (P3), Phase 5 (P5), and brucite, but the mass partitioning of these phases is highly dependent on H2O/MgCl2 and MgO/MgCl2 molar ratio as well as curing temperature and age. At room temperature, P3 is favored at lower water contents, however, P5 and/or brucite are favored to form as water availability increases. Thermodynamic calculations indicate that P3 is “more stable” than P5 at lower temperatures—an outcome which impacts the engineering properties, for example, strength and volume stability. The impacts of the accuracy and self‐consistency of currently available thermodynamic data and their implications on predicted phase assemblages are discussed.

STAY HEALTHY: AN AUSTRALIAN INSTITUTE OF SPORT ILLNESS PREVENTION PROJECT

BackgroundIllnesses affect the ability of an athlete to perform. Few studies investigate risk factors in athletes across disciplines.ObjectiveTo investigate risk factors for illness in athletes preparing for the Olympic Games.DesignCross-sectional.SettingAustralian...

Improving eye health using a child-to-child approach in Bariadi, Tanzania

Purpose: Vision Champions (VC) are children trained to perform simple eye health screening and share eye health messages among their community. Our objectives were to assess the ability of VC in identifying and referring children and the community with refractive error and obvious ocular disease and to assess the change in knowledge and practice of eye healthseeking behaviour of the community 3 months after the introduction of the Vision Champion Programme.Methods: We purposively sampled 600 households and interviewed 1051 participants in two phases with a close-ended questionnaire. The numbers of children screened, referred by the VC and those who attended the Vision Centre were recorded. The percentage of people who answered the questions correctly were compared between Phase 1 (P1) and Phase 2 (P2).Results: The VC shared their eye health messages with 6311 people, screened 7575 people’s vision and referred 2433 people for further care. The community were more aware that using eye ointment not prescribed by doctors (P1 = 58.96% vs. P2 = 72.75%) can lead to blindness. Participants were more aware that they should not administer eye drops in stock (P1 = 44.18% vs. P2 = 61.37%) or received from a friend or relative (P1 = 53.23% vs. P2 = 72.35%) if their eyes are red and painful.Conclusion: Children have the potential to effectively share eye health messages and conduct simple vision screening for their families and peers. Efforts are needed to sensitise the community to improve the referral or follow-up rate.

Influence of Finishing and Polishing Techniques and Abrasion on Transmittance and Roughness of Composite Resins.

The aim of this study was to evaluate the influence of finishing and polishing systems and toothbrush abrasion on transmittance (T) and surface roughness (Ra) of three composite resins (Filtek Z350 XT, Tetric N-Ceram, and IPS Empress Direct). Eighteen resin disks (10 mm diameter × 2 mm thick) finished by polyester strips had initial surface smoothness recorded, representing phase 1 (P1). Specimens were divided into three groups (n=6) according to the finishing/polishing instrument used (OneGloss, TopGloss, and Sof-Lex) to compose phase 2 samples (P2). Then specimens were subjected to 514 cycles of toothbrush simulation using a toothpaste slurry, with a constant load applied to soft bristles, and were then washed (phase 3=P3). After each phase, the specimens were examined by an optical profiler and spectrophotometer to measure Ra and T. Data were analyzed by analysis of variance, Tukey and Pearson tests. T values were statistically influenced by composite resin ( p=0.000) and phase of measurement ( p=0.000) factors, while the finishing/polishing system used ( p=0.741) did not affect T. On the other hand, Ra values were statistically affected by the factor finishing/polishing system ( p=0.000), but not by composite resin ( p=0.100) and phase of measurement ( p=0.451). Tetric N-Ceram and Empress Direct presented higher values of roughness when polished by OneGloss, while TopGloss and Sof-Lex showed a lower roughness. It can be concluded that composite resins transmitted more light after dental abrasion. Transmittance of composite resins was not modified by the distinct roughness created by finishing/polishing instruments.

Treatment of fish farm sludge supernatant by aerated filter beds and steel slag filters—effect of organic loading rate

The goal of our study was to develop an on-site cost-effective and extensive method for the treatment of supernatant of the sludge settling silo of fresh water fish farms. The main objectives of this study were 1) to determine the effect of the organic loading rate (OLR) on organic matter and nutrient removal efficiency of a pilot treatment system consisting of a series of aerated filter beds (AFBs) and electric arc furnace steel slag filters operated at different void hydraulic retention times (HRTV), 2) to validate the P-Hydroslag model as a design tool for slag filters and 3) to propose preliminary design options for fish farm sludge treatment. The 11.5 month experiment was divided into two phases: Phase 1 (P1) of 8.5 months with a low OLR to the AFBs of 0.015kg BOD5m−3 d−1, and Phase 2 (P2) of 3 months with a high OLR of 0.5kg BOD5m−3 d−1. The results showed that the OLR affected the organic matter mineralization and nitrification efficiency of AFBs. With a low OLR and an influent COD concentration of 320mgL−1, an average COD removal efficiency of 95% was observed while with a high OLR and an influent COD of 5400mgL−1, an average COD reduction of 65% was achieved. Due to the high OLR during P2, no nitrification took place probably due to the low availability of oxygen in the AFBs. The TP removal efficiency of the AFBs was 50% during P1 (influent of 5.2mgL−1), and 88% during P2 (influent of 110mgL−1). All SCs showed a high o-PO4 removal efficiency of >98% during P1 (average influent of 1.8mg P L−1, effluent of 0.04mg P L−1) and >85% during P2 (average influent of 8.7mg P L−1, effluent of 0.65mg P L−1) with a decrease in efficiency only observed over time in the SC that received the highest organic loading rate. It was concluded that with optimal loading rates, this compact biological and physicochemical semi-extensive treatment system offers a promising alternative to the high energy demand and maintenance treatment systems for organic matter and phosphorus removal, and that this treatment system could be applicable to other agro-environmental, municipal or residential effluents.

Phase 3 (P3) study of quizartinib (Q) or placebo (P) with induction (IND) and consolidation chemotherapy (CON) and as maintenance (MN) in patients (pts) with newly diagnosed (NDx) FLT3-ITD–positive acute myeloid leukemia (AML): the QuANTUM-First study.

TPS7073Background: Internal tandem duplications (ITDs) are commonly observed FLT3 mutations in AML and are a very poor prognostic factor for duration of response and overall survival (OS). While st...

A Phase 1 study to assess the safety, pharmacokinetics (PK), pharmacodynamics (PD) and antitumor activities of daily oral BAL101553, a novel tumor checkpoint controller (TCC) in adult patients with advanced solid tumors.

TPS2594Background: BAL101553 is the pro-drug of BAL27862, a novel small molecule TCC that promotes tumor cell death by modulating the spindle assembly checkpoint (SAC). In a completed Phase 1 (P1) ...

Constraints on the magmatic evolution of the oceanic crust from plagiogranite intrusions in the Oman ophiolite

We present major and trace element as well as Sr, Nd, and Hf isotope data on a suite of 87 plutonic rock samples from 27 felsic crustal intrusions in seven blocks of the Oman ophiolite. The rock compositions of the sample suite including associated more mafic rocks range from 48 to 79 wt% SiO2, i.e. from gabbros to tonalites. The samples are grouped into a Ti-rich and relatively light rare earth element (LREE)-enriched P1 group [(Ce/Yb)N > 0.7] resembling the early V1 lavas, and a Ti-poor and LREE-depleted P2 group [(Ce/Yb)N < 0.7] resembling the late-stage V2 lavas. Based on the geochemical differences and in agreement with previous structural and petrographic models, we define phase 1 (P1) and phase 2 (P2) plutonic rocks. Felsic magmas in both groups formed by extensive fractional crystallization of olivine, clinopyroxene, plagioclase, apatite, and Ti-magnetite from mafic melts. The incompatible element compositions of P1 rocks overlap with those from mid-ocean ridges but have higher Ba/Nb and Th/Nb trending towards the P2 rock compositions and indicating an influence of a subducting slab. The P2 rocks formed from a more depleted mantle source but show a more pronounced slab signature. These rocks also occur in the southern blocks (with the exception of the Tayin block) of the Oman ophiolite implying that the entire ophiolite formed above a subducting slab. Initial Nd and Hf isotope compositions suggest an Indian-MORB-type mantle source for the Oman ophiolite magmas. Isotope compositions and high Th/Nb in some P2 rocks indicate mixing of a melt from subducted sediment into this mantle.

LBA1_PR: Osimertinib as first-line treatment for EGFR mutation-positive advanced NSCLC: updated efficacy and safety results from two Phase I expansion cohorts

LBA1_PR: Osimertinib as first-line treatment for EGFR mutation-positive advanced NSCLC: updated efficacy and safety results from two Phase I expansion cohorts

LBA2_PR: Osimertinib (AZD9291) in pre-treated pts with T790M-positive advanced NSCLC: updated Phase 1 (P1) and pooled Phase 2 (P2) results

LBA2_PR: Osimertinib (AZD9291) in pre-treated pts with T790M-positive advanced NSCLC: updated Phase 1 (P1) and pooled Phase 2 (P2) results

Idelalisib Monotherapy and Durable Responses in Patients with Relapsed or Refractory Marginal Zone Lymphoma (MZL)

Idelalisib Monotherapy and Durable Responses in Patients with Relapsed or Refractory Marginal Zone Lymphoma (MZL)

Assessment of growth performance and meat quality of finishing pigs raised on the low plane of nutrition.

This study was performed to investigate the effects of the low plane of nutrition on growth and meat quality of finishing pigs. A total of 136 crossbred barrows and gilts weighing approximately 55 kg were allotted to 8 pens, with 17 animals housed per pen, in a 2 (sex) × 2 (nutrition) factorial arrangement of treatments. The animals allotted to a medium plane of nutrition (MPN) received a finisher phase 1 (P1) diet containing 3.47 Mcal DE/kg and 0.92 % lysine and a P2 diet containing 3.40 Mcal DE/kg and 0.78 % lysine for 35 d and 36/43 d, respectively; the animals allotted to the low plane of nutrition (LPN) received only a P2 diet containing 3.00 Mcal DE/kg and 0.68 % lysine 7 d longer than MPN. The animals were slaughtered following the feeding trial, after which the loin, ham, Boston butt, and belly were taken from a total of 24 animals, with the average live weight being 120 kg, and their physicochemical and sensory quality traits were analyzed. Average daily gain did not differ between MPN and LPN during either P1 or P2. Average daily feed intake was greater (P < 0.05) in LPN vs. MPN during both phases whereas the opposite was true for the gain:feed ratio. Backfat thickness (BFT) was less in LPN vs. MPN (21.7 vs. 24.1 mm at 115 kg). The plane of nutrition influenced no effect on any of the physicochemical characteristics of fresh loin, ham, or Boston butt analyzed in the present study. Fresh hams from LPN exhibited superior aroma and odor scores than those from MPN; however, sensory quality traits were not influenced by the plane of nutrition in other fresh primal cuts or cooked meat. Instead, fresh primal cuts and cooked meat from gilts rendered superior physicochemical characteristics and sensory scores, respectively, than those from barrows. Results suggest that the low plane of nutrition may be useful to increase the slaughter weight of finishing pigs with a moderately high BFT by virtue of its BFT-lowering effect with or without exerting a slightly positive influence on pork quality.

Risk factors for recurrent wheezing – International Study of Wheezing in Infants (EISL) phase 3

BackgroundWe aimed to identify factors associated with recurrent wheezing (RW) in infants in the first year of life living in the Southern region of São Paulo city and participating in the “Estudio Internacional de Sibilancias en Lactantes (EISL)” – phase 3 (P3). Methods1335 parents of infants who were attended in primary care health units in the Southern region of São Paulo city from 2009 to 2010 answered the EISL-P3 written questionnaire. The wheezing group was stratified in accordance to the frequency of wheezing episodes as occasional wheezing (OW, less than three episodes), or RW (three or more episodes). Wheezing-associated factors were evaluated using multivariate analysis and were expressed as odds ratio (OR) and 95% confidence interval (95%CI). ResultsThe most relevant factors related to OW were pneumonia (OR=3.10, 95%CI=1.68–5.73), hospitalisation due to pneumonia (OR=2.88, 95%CI=1.26–6.56) and recurrent upper respiratory infection (URI, OR=1.87, 95%CI=1.25–2.81). Regarding RW, recurrent URI (OR=5.34, 95%CI=3.83–7.45), pneumonia (OR=4.06, 95%CI=2.87–5.74) and asthmatic siblings (OR=3.02, 95%CI=1.67–5.45) were the most significantly associated factors. ConclusionsIn the present study, we found that recurrent URI, positive history of pneumonia and familiar history of asthma were the most relevant factors associated with RW. The precocious knowledge of these factors can enable the identification of the probable asthmatic infants and can improve both prevention strategies and treatment of these patients.

Health promotion 'on steroids': the value of an experiential approach to promote rapid HIV testing in NSW, Australia.

In 2012, there was a sharp increase in human immunodeficiency virus (HIV) notifications in New South Wales (NSW), Australia, following a 10-year period of relative stability. This increase, among other factors, triggered the development of a new HIV strategy that included renewed efforts to increase testing to improve early diagnosis, enable early treatment and reduce the risk of onward transmission. This article describes the activities conducted by NSW Health and partner organisations during November 2013 in the week before World AIDS Day (phase one (P1)) and HIV testing week in July 2014 (phase 2 (P2)). A model of pop-up HIV testing, new to Australia, was used to take testing to those most at risk of infection, and was promoted through social media and experiential techniques. During P1, an average of seven tests per hour were conducted at the pop-up service, compared with four tests per hour at a fast-track screening service in a nearby sexual health clinic. During HIV testing week, the campaign hashtag was mentioned an average of 56 times per day, following a baseline of six mentions per day one week before. The estimated total social media reach was 549,769 people via 459 posts. The pop-up testing model proved popular, and the use of social media and experiential techniques has extended the reach of the 'test more' messages. Further research is required to determine causality between specific HIV messaging and experiential techniques and testing rates.

Risk Factors for Recurrent Wheezing – International Study of Wheezing in Infants (EISL) Phase 3

Abstract Background We aimed to identify factors associated with recurrent wheezing (RW) in infants in the first year of life living in the Southern region of Sao Paulo city and participating in the “ Estudio Internacional de Sibilancias en Lactantes (EISL)” – phase 3 (P3). Methods 1335 parents of infants who were attended in primary care health units in the Southern region of Sao Paulo city from 2009 to 2010 answered the EISL-P3 written questionnaire. The wheezing group was stratified in accordance to the frequency of wheezing episodes as occasional wheezing (OW, less than three episodes), or RW (three or more episodes). Wheezing-associated factors were evaluated using multivariate analysis and were expressed as odds ratio (OR) and 95% confidence interval (95%CI). Results The most relevant factors related to OW were pneumonia (OR = 3.10, 95%CI = 1.68–5.73), hospitalisation due to pneumonia (OR = 2.88, 95%CI = 1.26–6.56) and recurrent upper respiratory infection (URI, OR = 1.87, 95%CI = 1.25–2.81). Regarding RW, recurrent URI (OR = 5.34, 95%CI = 3.83–7.45), pneumonia (OR = 4.06, 95%CI = 2.87–5.74) and asthmatic siblings (OR = 3.02, 95%CI = 1.67–5.45) were the most significantly associated factors. Conclusions In the present study, we found that recurrent URI, positive history of pneumonia and familiar history of asthma were the most relevant factors associated with RW. The precocious knowledge of these factors can enable the identification of the probable asthmatic infants and can improve both prevention strategies and treatment of these patients.

THU0145 Association of Mean Changes in Laboratory Safety Parameters with C-Reactive Protein at Baseline and Week 12 in Rheumatoid Arthritis Patients Treated with Tofacitinib

BackgroundTofacitinib is a novel, oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). Changes in laboratory parameters observed during tofacitinib treatment included mean increases in low (LDL) and...

Correlation between phase 2 clinical trial design and subsequent phase 3 outcome.

2549 Background: Randomized phase 2 (RP2) trials have been postulated to better predict phase 3 (P3) outcome than single arm trials. The aim of this study was to determine which characteristics of ...

Integrated nonclinical and clinical risk assessment to obviate the need for a dedicated QTc study of ixazomib citrate (MLN9708) in cancer patients (pts).

2553 Background: Ixazomib citrate is an investigational oral proteasome inhibitor in phase 3 (P3) clinical development. It is expected to have a favorable cardiac safety profile based on weak in vi...

PO70 CLINICAL BENEFIT OF FULVESTRANT IN POSTMENOPAUSAL WOMEN WITH ADVANCED BREAST CANCER ACCORDING TO PRIOR THERAPY

concurrent trastuzumab or RDI. G3/4 neutropenia was commonly seen. FN was documented in 5 pts (7.1%), although, all of them were G3 and resolved within 7 days. Other hematologic or non-hematologic toxicities were mild and tolerable. Conclusions: In Japan phase 2 (P2) study, 80 MBC pts who had received a median of 2 prior regimens obtained progression free of 112.0 days and OS of 331.0 days with 13.6% of incidence of FN by eribulin monotherapy (Aogi K, Ann Oncol, 2012). Comparing with Japan P2 study, our practice revealed lower RDI (68.05 versus 87.50%), although, sufficient disease controlling (median TTF of 119.0 days with eribulin monotherapy) with acceptable toxicities was obtained. These results suggest that eribulin has wide therapeutic window, and useful in managing MBC in practice.