Crustal structure of the Borderland-Continent Transition Zone of southern California adjacent to Los Angeles

We use data from the onshore-offshore component of Los Angeles Region Seismic Experiment (LARSE) to model the broad-scale features of the midcrust to upper mantle beneath a north-south transect that spans the continental borderland in the Los Angeles, California, region. We have developed an analysis method for wide-angle seismic data that consists primarily of refractions, lacks near-offset recordings, and contains wide gaps in coverage. Although the data restrict the analysis to the modeling of broad-scale structure, the technique allows one to explore the limits of the data and determine the resolving power of the data set. The resulting composite velocity model constrains the crustal thickness and location and width of the continent-Borderland transition zone. We find that the mid to lower crust layer velocities of the Inner Borderland are slightly lower than the corresponding layers in the average southern California crust model, while the upper mantle velocity is significantly higher. The data require the Moho to deepen significantly to the north. We constrain the transition zone to initiate between the offshore slope and the southwest Los Angeles Basin. If the Inner Borderland crust is 22 km thick, then the transition zone is constrained to initiate within a 2 km wide region beneath the southwest Los Angeles Basin, and have a width of 20–25 km. The strong, coherent, and continuous Pn phase suggests the Moho is coherent and laterally continuous beneath the Inner Borderland and transition zone. The Inner California Borderland seems to be modified and thickened oceanic crust, with the oceanic upper mantle intact beneath it

O desafio do envelhecimento demográfico

A crescente importância política, económica e social dos países em vias de desenvolvimento, a evolução rápida da sua população fez concentrar, durante o século XX, as atenções da opinião pública quase exclusivamente no crescimento demográfico. Quando se falava em população, falava-se sempre no receio das consequências da explosão demográfica. Os cenários elaborados pelas Nações Unidas, na segunda metade do século XX, apontavam para um mundo, no final do século XXI, com uma população próxima dos 20 milhares de milhão de habitantes (quatro vezes mais a população mundial existente em 1990 - 5 milhares de milhão)

Remembering the forgotten child: the role of immune checkpoint inhibition in patients with human immunod eficiency virus and cancer.

Patients with human immunodeficiency virus (HIV) infection have a high risk of developing virally-mediated cancers. These tumors have several features that could make them vulnerable to immune checkpoint inhibitors (ICIs) including, but not limited to, increased expression of the CTLA-4 and PD-1 checkpoints on their CD4+ T cells. Even so, HIV-positive patients are generally excluded from immunotherapy cancer clinical trials due to safety concerns. Hence, only case series have been published regarding HIV-positive patients with cancer who received ICIs, but these reports of individuals with a variety of malignancies demonstrate that ICIs have significant activity, exceeding a 65% objective response rate in Kaposi sarcoma. Furthermore, high-grade immune toxicities occurred in fewer than 10% of treated patients. The existing data suggest that the underlying biologic mechanisms that mediate development of cancer in HIV-infected patients should render them susceptible to ICI treatment. Preliminary, albeit limited, clinical experience indicates that checkpoint blockade is both safe and efficacious in this setting. Additional clinical trials that include HIV-positive patients with cancer are urgently needed

Strategies to improve retention in randomised trials: a Cochrane systematic review and meta-analysis

Objective: To quantify the effect of strategies to improve retention in randomised trials.<p></p> Design: Systematic review and meta-analysis.<p></p> Data sources Sources searched: MEDLINE, EMBASE, PsycINFO, DARE, CENTRAL, CINAHL, C2-SPECTR, ERIC, PreMEDLINE, Cochrane Methodology Register, Current Controlled Trials metaRegister, WHO trials platform, Society for Clinical Trials (SCT) conference proceedings and a survey of all UK clinical trial research units.<p></p> Review: methods Included trials were randomised evaluations of strategies to improve retention embedded within host randomised trials. The primary outcome was retention of trial participants. Data from trials were pooled using the fixed-effect model. Subgroup analyses were used to explore the heterogeneity and to determine whether there were any differences in effect by the type of strategy.<p></p> Results: 38 retention trials were identified. Six broad types of strategies were evaluated. Strategies that increased postal questionnaire responses were: adding, that is, giving a monetary incentive (RR 1.18; 95% CI 1.09 to 1.28) and higher valued incentives (RR 1.12; 95% CI 1.04 to 1.22). Offering a monetary incentive, that is, an incentive given on receipt of a completed questionnaire, also increased electronic questionnaire response (RR 1.25; 95% CI 1.14 to 1.38). The evidence for shorter questionnaires (RR 1.04; 95% CI 1.00 to 1.08) and questionnaires relevant to the disease/condition (RR 1.07; 95% CI 1.01 to 1.14) is less clear. On the basis of the results of single trials, the following strategies appeared effective at increasing questionnaire response: recorded delivery of questionnaires (RR 2.08; 95% CI 1.11 to 3.87); a ‘package’ of postal communication strategies (RR 1.43; 95% CI 1.22 to 1.67) and an open trial design (RR 1.37; 95% CI 1.16 to 1.63). There is no good evidence that the following strategies impact on trial response/retention: adding a non-monetary incentive (RR=1.00; 95% CI 0.98 to 1.02); offering a non-monetary incentive (RR=0.99; 95% CI 0.95 to 1.03); ‘enhanced’ letters (RR=1.01; 95% CI 0.97 to 1.05); monetary incentives compared with offering prize draw entry (RR=1.04; 95% CI 0.91 to 1.19); priority postal delivery (RR=1.02; 95% CI 0.95 to 1.09); behavioural motivational strategies (RR=1.08; 95% CI 0.93 to 1.24); additional reminders to participants (RR=1.03; 95% CI 0.99 to 1.06) and questionnaire question order (RR=1.00, 0.97 to 1.02). Also based on single trials, these strategies do not appear effective: a telephone survey compared with a monetary incentive plus questionnaire (RR=1.08; 95% CI 0.94 to 1.24); offering a charity donation (RR=1.02, 95% CI 0.78 to 1.32); sending sites reminders (RR=0.96; 95% CI 0.83 to 1.11); sending questionnaires early (RR=1.10; 95% CI 0.96 to 1.26); longer and clearer questionnaires (RR=1.01, 0.95 to 1.07) and participant case management by trial assistants (RR=1.00; 95% CI 0.97 to 1.04).<p></p> Conclusions: Most of the trials evaluated questionnaire response rather than ways to improve participants return to site for follow-up. Monetary incentives and offers of monetary incentives increase postal and electronic questionnaire response. Some strategies need further evaluation. Application of these results would depend on trial context and follow-up procedures.<p></p&gt

The Pulmonary Microbiome in Cystic Fibrosis

The chronic colonisation of the lower airways by bacterial pathogens is the leading cause of morbidity and mortality in patients with cystic fibrosis (CF). The use of novel culture-independent techniques such as next-generation sequencing (NGS) to analyse the lungs has allowed us to further understand the diversity, the complexity, the effects of acute exacerbations and the use of antibiotics on the bacterial communities. The understanding of the CF microbiome to airway disease remains a fascinating area of research; it presents new opportunities for disease management in CF and has the potential to explore the effects of cystic fibrosis transmembrane conductance regulator (CFTR) modulators. It also allows further appreciation regarding the roles played by anaerobic organisms within the CF airways. It is also of interest that a number of studies have demonstrated that the fluctuations of microbiome are not necessarily associated with the patient’s clinical status. Despite the available evidence, there remain many challenges that must be overcome if microbiome profiling is going to influence future clinical practice. The effects of fungus and the emergence of nontuberculous mycobacteria in CF are also briefly discussed in this chapter

A Standard Input Format for Computer Codes Which Solve Stochastic Programs with Recourse and a Library of Utilities to Simplify its Use

We explain our suggestions for standardizing input formats for computer codes which solve stochastic programs with recourse. The main reason to set some conventions is to allow programs implementing different methods of solution to be used interchangeably. The general philosophy behind our design is a) to remain fairly faithful to the de facto standard for the statement of LP problems established by IBM for use with MPSX and subsequently adopted by the authors of MINOS, b) to provide sufficient flexibility so that a variety of problems may be expressed in the standard format, c) to allow problems originally formulated as deterministic LP to be converted to stochastic problems with a minimum of effort, d) to permit new options to be added as the need arises, and e) to provide some routines to facilitate the task of reading files specified in the standard format

The static stress change triggering model: Constraints from two southern California aftershock sequences

Static stress change has been proposed as a mechanism of earthquake triggering. We quantitatively evaluate this model for the apparent triggering of aftershocks by the 1992 M_W 7.3 Landers and 1994 M_W 6.7 Northridge earthquakes. Specifically, we test whether the fraction of aftershocks consistent with static stress change triggering is greater than the fraction of random events which would appear consistent by chance. Although static stress changes appear useful in explaining the triggering of some aftershocks, the model's capability to explain aftershock occurrence varies significantly between sequences. The model works well for Landers aftershocks. Approximately 85% of events between 5 and 75 km distance from the mainshock fault plane are consistent with static stress change triggering, compared to ∼50% of random events. The minimum distance is probably controlled by limitations of the modeling, while the maximum distance may be because static stress changes of <0.01 MPa trigger too few events to be detected. The static stress change triggering model, however, can not explain the first month of the Northridge aftershock sequence significantly better than it explains a set of random events. The difference between the Landers and Northridge sequences may result from differences in fault strength, with static stress changes being a more significant fraction of the failure stress of weak Landers-area faults. Tectonic regime, regional stress levels, and fault strength may need to be incorporated into the static stress change triggering model before it can be used reliably for seismic hazard assessment

Use of strategies to improve retention in primary care randomised trials: a qualitative study with in-depth interviews

Objective To explore the strategies used to improve retention in primary care randomised trials.&lt;p&gt;&lt;/p&gt; Design Qualitative in-depth interviews and thematic analysis.&lt;p&gt;&lt;/p&gt; Participants 29 UK primary care chief and principal investigators, trial managers and research nurses.&lt;p&gt;&lt;/p&gt; Methods In-depth face-to-face interviews.&lt;p&gt;&lt;/p&gt; Results Primary care researchers use incentive and communication strategies to improve retention in trials, but were unsure of their effect. Small monetary incentives were used to increase response to postal questionnaires. Non-monetary incentives were used although there was scepticism about the impact of these on retention. Nurses routinely used telephone communication to encourage participants to return for trial follow-up. Trial managers used first class post, shorter questionnaires and improved questionnaire designs with the aim of improving questionnaire response. Interviewees thought an open trial design could lead to biased results and were negative about using behavioural strategies to improve retention. There was consensus among the interviewees that effective communication and rapport with participants, participant altruism, respect for participant's time, flexibility of trial personnel and appointment schedules and trial information improve retention. Interviewees noted particular challenges with retention in mental health trials and those involving teenagers.&lt;p&gt;&lt;/p&gt; Conclusions The findings of this qualitative study have allowed us to reflect on research practice around retention and highlight a gap between such practice and current evidence. Interviewees describe acting from experience without evidence from the literature, which supports the use of small monetary incentives to improve the questionnaire response. No such evidence exists for non-monetary incentives or first class post, use of which may need reconsideration. An exploration of barriers and facilitators to retention in other research contexts may be justified.&lt;p&gt;&lt;/p&gt