Crown ether decorated silicon photonics for safeguarding against lead poisoning

Lead (Pb2+) toxification in society is one of the most concerning public health crisis that remains unaddressed. The exposure to Pb2+ poisoning leads to a multitude of enduring health issues, even at the part-per-billion scale (ppb). Yet, public action dwarfs its impact. Pb2+ poisoning is estimated to account for 1 million deaths per year globally, which is in addition to its chronic impact on children. With their ring-shaped cavities, crown ethers are uniquely capable of selectively binding to specific ions. In this work, for the first time, the synergistic integration of highly-scalable silicon photonics, with crown ether amine conjugation via Fischer esterification in an environmentally-friendly fashion is demonstrated. This realises a photonic platform that enables the in-situ, highly-selective and quantitative detection of various ions. The development dispels the existing notion that Fischer esterification is restricted to organic compounds, laying the ground for subsequent amine conjugation for various crown ethers. In this work, the platform is engineered for Pb2+ detection, demonstrating a large dynamic detection range of 1 - 262000 ppb with high selectivity against a wide range of relevant ions. These results indicate the potential for the pervasive implementation of the technology to safeguard against ubiquitous lead poisoning in our society

Effects of hospital facilities on patient outcomes after cancer surgery: an international, prospective, observational study

Background Early death after cancer surgery is higher in low-income and middle-income countries (LMICs) compared with in high-income countries, yet the impact of facility characteristics on early postoperative outcomes is unknown. The aim of this study was to examine the association between hospital infrastructure, resource availability, and processes on early outcomes after cancer surgery worldwide.Methods A multimethods analysis was performed as part of the GlobalSurg 3 study-a multicentre, international, prospective cohort study of patients who had surgery for breast, colorectal, or gastric cancer. The primary outcomes were 30-day mortality and 30-day major complication rates. Potentially beneficial hospital facilities were identified by variable selection to select those associated with 30-day mortality. Adjusted outcomes were determined using generalised estimating equations to account for patient characteristics and country-income group, with population stratification by hospital.Findings Between April 1, 2018, and April 23, 2019, facility-level data were collected for 9685 patients across 238 hospitals in 66 countries (91 hospitals in 20 high-income countries; 57 hospitals in 19 upper-middle-income countries; and 90 hospitals in 27 low-income to lower-middle-income countries). The availability of five hospital facilities was inversely associated with mortality: ultrasound, CT scanner, critical care unit, opioid analgesia, and oncologist. After adjustment for case-mix and country income group, hospitals with three or fewer of these facilities (62 hospitals, 1294 patients) had higher mortality compared with those with four or five (adjusted odds ratio [OR] 3.85 [95% CI 2.58-5.75]; p<0.0001), with excess mortality predominantly explained by a limited capacity to rescue following the development of major complications (63.0% vs 82.7%; OR 0.35 [0.23-0.53]; p<0.0001). Across LMICs, improvements in hospital facilities would prevent one to three deaths for every 100 patients undergoing surgery for cancer.Interpretation Hospitals with higher levels of infrastructure and resources have better outcomes after cancer surgery, independent of country income. Without urgent strengthening of hospital infrastructure and resources, the reductions in cancer-associated mortality associated with improved access will not be realised

A mixed methods process evaluation of a person-centred falls prevention program

Background RESPOND is a telephone-based falls prevention program for older people who present to a hospital emergency department (ED) with a fall. A randomised controlled trial (RCT) found RESPOND to be effective at reducing the rate of falls and fractures, compared with usual care, but not fall injuries or hospitalisations. This process evaluation aimed to determine whether RESPOND was implemented as planned, and identify implementation barriers and facilitators. Methods A mixed-methods evaluation was conducted alongside the RCT. Evaluation participants were the RESPOND intervention group (n=263) and the clinicians delivering RESPOND (n=7). Evaluation data were collected from participant recruitment and intervention records, hospital administrative records, audio-recordings of intervention sessions, and participant questionnaires. The Rochester Participatory Decision-Making scale (RPAD) was used to evaluate person-centredness (score range 0 (worst) - 9 (best)). Process factors were compared with pre-specified criteria to determine implementation fidelity. Six focus groups were held with participants (n=41), and interviews were conducted with RESPOND clinicians (n=6). Quantitative data were analysed descriptively and qualitative data thematically. Barriers and facilitators to implementation were mapped to the ‘Capability, Opportunity, Motivation – Behaviour’ (COM-B) behaviour change framework. Results RESPOND was implemented at a lower dose than the planned 10 hours over six months, with a median (IQR) of 2.9 hours (2.1, 4). The majority (76%) of participants received their first intervention session within one month of hospital discharge. Clinicians delivered the program in a person-centred manner with a median (IQR) RPAD score of 7 (6.5, 7.5) and 87% of questionnaire respondents were satisfied with the program. The reports from participants and clinicians suggested that implementation was facilitated by the use of positive and personally relevant health messages. Complex health and social issues were the main barriers to implementation. Conclusions RESPOND was person-centred and reduced falls and fractures at a substantially lower dose, using fewer resources, than anticipated. However, the low dose delivered may account for the lack of effect on falls injuries and hospitalisations. The results from this evaluation provide detailed information to guide future implementation of RESPOND of similar programs. Trial registration: This study was registered with the Australian New Zealand Clinical Trials Registry, number ACTRN12614000336684 (27 March 2014)

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Thermoelectric properties of N-type Bi2Te2.7Se0.3 and P-type Bi0.5Sb1.5Te3 films for micro-cooler applications

Bi2Te3 and its solid solution remain the state-of-the-art thermoelectric materials for refrigeration applications in microelectronics industry, such as dissipating the heat generated by various devices. The fabrication method and associated processing parameters are to be optimised to get desirable composition exhibiting better electrical and thermal transport properties. Carrier concentration and mobility are found to be crucial in achieving high thermoelectric cooling efficiency and energy conversion. In this paper, we present the fabrication and analysis of thermoelectric thin films deposited by RF-magnetron sputtering from n-type Bi2Te2.7Se0.3 and p-type Bi0.5Sb1.5Te3 targets on a silicon substrate. X-ray diffraction, Scanning electron microscopy combined with energy dispersive spectrometry, electrical resistivity, Seebeck coefficient and thermal diffusivity measurements were used for the thermoelectric thin films characterization. We studied the effect of sputtering process parameters, on the structural, electrical and thermal transport characteristics of films. The observed results demonstrate both n-and p-type doped Bi2Te3 films exhibit desirable properties and could be potential candidates for thermoelectric micro-cooler applications

Isolation of a Peptide That Binds to Pseudomonas aeruginosa Lytic Bacteriophage

Antimicrobial resistance is a global health threat that is exacerbated by the overuse and misuse of antibiotics in medicine and agriculture. As an alternative to conventional antimicrobial drugs, phage therapy involves the treatment of infected patients with a bacteriophage that naturally destroys bacterial pathogens. With the re-emergence of phage therapy, novel tools are needed to study phages. In this work we set out to screen and isolate peptide candidates that bind to phages and act as affinity tags. Such peptides functionalized with an imaging agent could serves as versatile tools for tracking and imaging of phages. Specifically, we screened a phage display library for peptides that bind to the Good Vibes phage (GV), which lyses the bacterial pathogen Pseudomonas aeruginosa. Isolated monoclonal library phages featured a highly conserved consensus motif, LPPIXRX. The corresponding peptide WDLPPIGRLSGN was synthesized with a GGGSK linker and conjugated to cyanine 5 or biotin. The specific binding of the LPPIXRX motif to GV in vitro was confirmed using an enzyme-linked immunosorbent assay. We demonstrated imaging and tracking of GV in bacterial populations using the fluorescent targeting peptide and flow cytometry. In conclusion, we developed fluorescent labeled peptides that can bind to bacteriophage GV specifically, which may enable real-time analysis of phage in vivo and monitor the efficacy of phage therapy

Changes in immune cell populations following KappaMab, lenalidomide and low‐dose dexamethasone treatment in multiple myeloma

Abstract Objectives Lenalidomide (LEN) is used to treat multiple myeloma (MM) and shows in vitro synergy with KappaMab (KM), a chimeric antibody specific for Kappa Myeloma antigen, an antigen exclusively expressed on the surface of kappa‐restricted MM cells. Lenalidomide, dexamethasone (DEX) and KM control MM via multiple immunomodulatory mechanisms; however, there are several additional effects of the drug combination on immune cells. Lenalidomide can increase T cell and NKT cell cytotoxicity and dendritic cell (DC) activation in vitro. We investigated the immune cell populations in bone marrow of patients treated with KM, LEN and low‐dose DEX in kappa‐restricted relapsed/refractory MM ex vivo and assessed association of those changes with patient outcome. Methods A cohort (n = 40) of patients with kappa‐restricted relapsed/refractory MM, treated with KM, LEN and low‐dose DEX, was analysed using a mass cytometry panel that allowed identification of immune cell subsets. Clustering analyses were used to determine significant changes in immune cell populations at time periods after treatment. Results We found changes in five DC and 17 T‐cell populations throughout treatment. We showed an increase in activated conventional DC populations, a decrease in immature/precursor DC populations, a decrease in activated CD4 T cells and an increase in effector‐memory CD4 T cells and effector CD8 T cells, indicating an activated immune response. Conclusion These data characterise the effects of LEN, DEX, and KM treatment on non‐target immune cells in MM. Treatment may support destruction of MM cells by both direct action and indirect mechanisms via immune cells

Effect of sputtering process parameters on the thermoelectric properties of P and N-type Bi2Te3 films

Thermoelectric is an ever evolving field that serves many critical needs (cooling and power generation) in the industry. The key objective of this work is to fabricate Bismuth Telluride (Bi2Te3) thin-films by varying the various process parameters using a radio-frequency (RF) magnetron sputtering disposition technique. Characterization methods such as four point probe resistivity, surface profiler, atomic force microscopy (AFM), X-ray diffraction (XRD), Seebeck coefficient and thermal diffusivity are performed on the N and P-type Bi2Te3 films. The samples are analysed for their electrical properties in relation to the evolved microstructures, for how the process parameters of sputtering and annealing affect these changes. The results demonstrate that N-Type film (S2) processed using sputtering parameters of 7mT, 100W, 50sccm of argon flow under room temperature for 30mins with no annealing and the P-Type film processed using sputtering parameters of 7mT, 100W, 60sccm under room temperature for 30mins with institute annealing at 200oC for 2h exhibit desirable thermoelectric properties suitable for cooling application in microelectronic and optoelectronic devices, optimizing their performance and reliability