Bayesian optimization with a finite budget: An approximate dynamic programming approach

We consider the problem of optimizing an expensive objective function when a finite budget of total evaluations is prescribed. In that context, the optimal solution strategy for Bayesian optimization can be formulated as a dynamic programming instance. This results in a complex problem with uncountable, dimension-increasing state space and an uncountable control space. We show how to approximate the solution of this dynamic programming problem using rollout, and propose rollout heuristics specifically designed for the Bayesian optimization setting. We present numerical experiments showing that the resulting algorithm for optimization with a finite budget outperforms several popular Bayesian optimization algorithms

Advances in Bayesian Optimization with Applications in Aerospace Engineering

Optimization requires the quantities of interest that define objective functions and constraints to be evaluated a large number of times. In aerospace engineering, these quantities of interest can be expensive to compute (e.g., numerically solving a set of partial differential equations), leading to a challenging optimization problem. Bayesian optimization (BO) is a class of algorithms for the global optimization of expensive-to-evaluate functions. BO leverages all past evaluations available to construct a surrogate model. This surrogate model is then used to select the next design to evaluate. This paper reviews two recent advances in BO that tackle the challenges of optimizing expensive functions and thus can enrich the optimization toolbox of the aerospace engineer. The first method addresses optimization problems subject to inequality constraints where a finite budget of evaluations is available, a common situation when dealing with expensive models (e.g., a limited time to conduct the optimization study or limited access to a supercomputer). This challenge is addressed via a lookahead BO algorithm that plans the sequence of designs to evaluate in order to maximize the improvement achieved, not only at the next iteration, but once the total budget is consumed. The second method demonstrates how sensitivity information, such as gradients computed with adjoint methods, can be incorporated into a BO algorithm. This algorithm exploits sensitivity information in two ways: first, to enhance the surrogate model, and second, to improve the selection of the next design to evaluate by accounting for future gradient evaluations. The benefits of the two methods are demonstrated on aerospace examples

Patient and parent perspectives of adolescent Laparoscopic Adjustable Gastric Banding (LAGB)

Introduction Adolescent obesity is a significant global health challenge and severely obese adolescents commonly experience serious medical and psychosocial challenges. Consequently, severe adolescent obesity is increasingly being treated surgically. The limited available research examining the effectiveness of adolescent bariatric surgery focuses primarily on bio-medical outcomes. There is a need for a more comprehensive understanding of the behavioural, emotional and social factors which affect adolescents’ and parents’ experience of weight-loss surgery. Materials/Methods Patient and parents’ perspectives of adolescent LAGB were examined using a qualitative research methodology. Individual, semi-structured interviews were conducted with eight adolescent patients and five parents. Thematic analysis was used to identify key themes in the qualitative data. Results Patients and parents generally considered adolescent LAGB to be a life-changing experience, resulting in physical and mental health benefits. Factors considered to facilitate weight-loss following surgery included parental support and adherence to treatment guidelines. Many adolescents reported experiencing surgical weight-loss stigma and challenging interpersonal outcomes after weight-loss for which they felt unprepared. Conclusion Patients and parents perceived LAGB positively. There are opportunities to improve both the experience and outcomes of adolescent LAGB through parental education and enhancements to surgical aftercare programs

Digital Spatial Profiling identifies distinct patterns of immuno-oncology-related gene expression within oropharyngeal tumours in relation to HPV and p16 status

BACKGROUND: The incidence of oropharyngeal cancer (OPC) is increasing, due mainly to a rise in Human Papilloma Virus (HPV)-mediated disease. HPV-mediated OPC has significantly better prognosis compared with HPV-negative OPC, stimulating interest in treatment de-intensification approaches to reduce long-term sequelae. Routine clinical testing frequently utilises immunohistochemistry to detect upregulation of p16 as a surrogate marker of HPV-mediation. However, this does not detect discordant p16-/HPV+ cases and incorrectly assigns p16+/HPV- cases, which, given their inferior prognosis compared to p16+/HPV+, may have important clinical implications. The biology underlying poorer prognosis of p16/HPV discordant OPC requires exploration.METHODS: GeoMx digital spatial profiling was used to compare the expression patterns of selected immuno-oncology-related genes/gene families (n=73) within the tumour and stromal compartments of formalin-fixed, paraffin-embedded OPC tumour tissues (n=12) representing the three subgroups, p16+/HPV+, p16+/HPV- and p16-/HPV-.RESULTS: Keratin (multi KRT) and HIF1A, a key regulator of hypoxia adaptation, were upregulated in both p16+/HPV- and p16-/HPV- tumours relative to p16+/HPV+. Several genes associated with tumour cell proliferation and survival (CCND1, AKT1 and CD44) were more highly expressed in p16-/HPV- tumours relative to p16+/HPV+. Conversely, multiple genes with potential roles in anti-tumour immune responses (immune cell recruitment/trafficking, antigen processing and presentation), such as CXCL9, CXCL10, ITGB2, PSMB10, CD74, HLA-DRB and B2M, were more highly expressed in the tumour and stromal compartments of p16+/HPV+ OPC versus p16-/HPV- and p16+/HPV-. CXCL9 was the only gene showing significant differential expression between p16+/HPV- and p16-/HPV- tumours being upregulated within the stromal compartment of the former. CONCLUSIONS: In terms of immune-oncology-related gene expression, discordant p16+/HPV- OPCs are much more closely aligned with p16-/HPV-OPCs and quite distinct from p16+/HPV+ tumours. This is consistent with previously described prognostic patterns (p16+/HPV+ &gt;&gt; p16+/HPV- &gt; p16-/HPV-) and underlines the need for dual p16 and HPV testing to guide clinical decision making.</p

Defects in NK cell immunity of pediatric cancer patients revealed by deep immune profiling

Systemic immunity plays an important role in cancer immune surveillance and response to therapy, but little is known about the immune status of children with solid cancers. We performed a high-dimensional single-cell analysis of systemic immunity in 50 treatment-naïve pediatric cancer patients, comparing them to age-matched healthy children. Children with cancer had a lower frequency of peripheral NK cells, which was not due to tumour sequestration, had lower surface levels of activating receptors and increased levels of the inhibitory NKG2A receptor. Furthermore, the NK cells of pediatric cancer patients were less mature and less cytotoxic when tested in vitro. Culture of these NK cells with interleukin-2 restored their cytotoxicity. Collectively, our data show that NK cells in pediatric cancer patients are impaired through multiple mechanisms and identifies rational strategies to restore their functionality

Zooming in on the intracellular microbiome composition of bacterivorous <i>Acanthamoeba</i> isolates

Acanthamoeba, a free-living amoeba in water and soil, is an emerging pathogen causing severe eye infection known as Acanthamoeba keratitis. In its natural environment, Acanthamoeba performs a dual function as an environmental heterotrophic predator and host for a range of microorganisms that resist digestion. Our objective was to characterize the intracellular microorganisms of phylogenetically distinct Acanthamoeba spp. isolated in Australia and India through directly sequencing 16S rRNA amplicons from the amoebae. The presence of intracellular bacteria was further confirmed by in situ hybridization and electron microscopy. Among the 51 isolates assessed, 41% harboured intracellular bacteria which were clustered into four major phyla: Pseudomonadota (previously known as Proteobacteria), Bacteroidota (previously known as Bacteroidetes), Actinomycetota (previously known as Actinobacteria), and Bacillota (previously known as Firmicutes). The linear discriminate analysis effect size analysis identified distinct microbial abundance patterns among the sample types; Pseudomonas species was abundant in Australian corneal isolates (P &lt; 0.007), Enterobacteriales showed higher abundance in Indian corneal isolates (P &lt; 0.017), and Bacteroidota was abundant in Australian water isolates (P &lt; 0.019). The bacterial beta diversity of Acanthamoeba isolates from keratitis patients in India and Australia significantly differed (P &lt; 0.05), while alpha diversity did not vary based on the country of origin or source of isolation (P &gt; 0.05). More diverse intracellular bacteria were identified in water isolates as compared with clinical isolates. Confocal and electron microscopy confirmed the bacterial cells undergoing binary fission within the amoebal host, indicating the presence of viable bacteria. This study sheds light on the possibility of a sympatric lifestyle within Acanthamoeba, thereby emphasizing its crucial role as a bunker and carrier of potential human pathogens

Asymmetric ketone hydroboration catalyzed by alkali metal complexes derived from BINOL ligands

The ability of alkali metal complexes featuring functionalized BINOL-derived ligands to catalyze ketone hydroboration reactions was explored. The reduced products were formed in excellent yield and with variable enantioselectivities dependent upon the nature of the ligand and the alkali metal cation

Women's beliefs about breast cancer causation in a breast cancer case-control study

Objective: Our study sought to ascertain women's beliefs about breast cancer risk factors and whether these beliefs differed by demographic factors and personal and family history of breast cancer. Methods: Participants in a case-control study of breast cancer rated the effect of 37 exposures on the risk of being diagnosed with breast cancer. Chi-square tests were undertaken to measure differences in responses between cases and controls for each exposure. Logistic regression was undertaken to ascertain whether demographic factors and personal and family history of breast cancer affected participants' ability to correctly identify known breast cancer risk factors. Results: A total of 2742 participants completed the questionnaire, comprising 1109 cases and 1633 controls. Significant differences (p&lt;0.05) between cases and controls were found for 16 of the 37 exposures. Younger women and university-educated women were more likely to correctly identify known breast cancer risk factors. Women's perceptions about the effect of alcohol consumption on breast cancer risk, particularly regarding red wine, differed from that reported in the literature. Conclusions: Beliefs about risk factors for breast cancer may differ between cases and controls. Public health initiatives aimed at increasing awareness of breast cancer risk factors should consider that women's beliefs may differ by demographic factors and family history of breast cancer