IceCube's neutrinos: galactic or extra-galactic?

The exact origin and production method of the astrophysical neutrino, a subatomic particle that is very difficult to detect, is yet to be confirmed. Here, two source scenarios for the origin of the neutrino are considered: Galactic and extra-galactic. In the Galactic scenario, neutrinos are searched for from the disk and the halo of the Milky Way, whereas in the extra-galactic case neutrinos might be coming from Active Galactic Nuclei, Starburst Galaxies and other highly energetic regions of the Universe. The IceCube Neutrino Observatory has detected an astrophysical neutrino intensity which may reveal the origin of these neutrinos. The Milky Way is not a unique galaxy. If it were to produce some fraction of the neutrinos that IceCube detects then there must be other similar spiral galaxies in the Universe also contributing to the intensity. This could create a contradiction of how many other Milky Way-like galaxies there would be allowed in the rest of the Universe if the assumption is made that the Milky Way produces nearly all of IceCube’s neutrinos. The overall number density of Milky Way-like objects in the Universe can be calculated for different Galactic source distributions. The neutrino sources could be distributed throughout the halo of the Galaxy or confined to the Galactic disk. By considering various models and calculating the number density of equivalent Milky Way-like galaxies in the rest of the Universe, constraints are placed on the fraction of the IceCube intensity that could be coming purely from the Milky Way. According to the results of this research it is ultimately found that, under the simplifying assumption that the halo is spherical, the halo of the Milky Way cannot account for all of IceCube’s neutrinos and under certain assumptions the disks of Milky Way-like galaxies cannot be the sole origin of neutrinos in light of experimental observations.Thesis (MPhil) -- University of Adelaide, School of Physical Sciences, 201

Introduced Species and the Issue of Animal Welfare

Recently, considerable debate has been heard about the control or elimination of introduced or exotic animals on publicly held U.S. lands. Species introductions, whether intentional or unintentional, seem to be an inevitable result of human activities. Still, they may result in economic and ecological problems: It has been estimated that over 90 percent of all such introductions have been harmful in some respect. Control of exotics can be accomplished through containment, shooting, poisoning, reintroduction of native predators, the introduction of disease organisms, live capture and removal, and reproductive inhibition

Introduced Species and the Issue of Animal Welfare

Recently, considerable debate has been heard about the control or elimination of introduced or exotic animals on publicly held U.S. lands. Species introductions, whether intentional or unintentional, seem to be an inevitable result of human activities, but they may result in both economic and ecological problems: It has been estimated that over 90 percent of all such introductions have been harmful in some respect. Control of exotics can be accomplished through containment, shooting, poisoning, reintroduction of native predators, introduction of disease organisms, live capture and removal, and reproductive inhibition. Those who must make decisions about the fate of introduced species need to seek a balance between the rights of the individual animals and preserving the viability of whole ecosystems. One important consideration is that, although the control of exotic animal populations may adversely affect individual sentient beings, inaction may cause widespread suffering to many species and consequent loss of biological diversity

Does group assessment impact BME attainment?

Assessment of student learning is fundamental in Higher Education (HE) reflecting academic standards and impacting on student satisfaction, position in league tables and graduate employment. Nonetheless, there is a BME (Black and Minority Ethnic) attainment gap, the difference in the proportion of BME and White students who attain a first class or 2.1 honours degree (even when controlled for prior attainment and entry profile), which is persistent across the HE sector. As assessment strategies play an essential role in determining degree attainment, we have reviewed the role of group assessment and whether this form of assessment specifically impacts on the BME attainment gap. Overall, this study provided evidence that assessed group work does not adversely impact BME students. In addition, the performance in BME/non-BME/mixed groups did not suggest any consistent difference, suggesting that the demographic composition of groups does not affect BME performance. Therefore, group work would appear to be an inclusive form of assessment that does not appear to lead or contribute to exacerbating the BME attainment gap

A systematic review and meta-analysis of CD22 CAR T-cells alone or in combination with CD19 CAR T-cells

Chimeric antigen receptor (CAR) T-cells are an emerging therapy for the treatment of relapsed/refractory B-cell malignancies. While CD19 CAR-T cells have been FDA-approved, CAR T-cells targeting CD22, as well as dual-targeting CD19/CD22 CAR T-cells, are currently being evaluated in clinical trials. This systematic review and meta-analysis aimed to evaluate the efficacy and safety of CD22-targeting CAR T-cell therapies. We searched MEDLINE, EMBASE, Web of Science, and the Cochrane Central Register of Controlled Trials from inception to March 3rd 2022 for full-length articles and conference abstracts of clinical trials employing CD22-targeting CAR T-cells in acute lymphocytic leukemia (ALL) and non-Hodgkin’s lymphoma (NHL). The primary outcome was best complete response (bCR). A DerSimonian and Laird random-effects model with arcsine transformation was used to pool outcome proportions. From 1068 references screened, 100 were included, representing 30 early phase studies with 637 patients, investigating CD22 or CD19/CD22 CAR T-cells. CD22 CAR T-cells had a bCR of 68% [95% CI, 53-81%] in ALL (n= 116), and 64% [95% CI, 46-81%] in NHL (n= 28) with 74% and 96% of patients having received anti-CD19 CAR T-cells previously in ALL and NHL studies respectively. CD19/CD22 CAR T-cells had a bCR rate of 90% [95% CI, 84-95%] in ALL (n= 297) and 47% [95% CI, 34-61%] in NHL (n= 137). The estimated incidence of total and severe (grade ≥3) CRS were 87% [95% CI, 80-92%] and 6% [95% CI, 3-9%] respectively. ICANS and severe ICANS had an estimated incidence of 16% [95% CI, 9-25%] and 3% [95% CI, 1-5%] respectively. Early phase trials of CD22 and CD19/CD22 CAR T-cells show high remission rates in ALL and NHL. Severe CRS or ICANS were (1)rare and dual-targeting did not increase toxicity. Variability in CAR construct, dose, and patient factors amongst studies limits comparisons, with long-term outcomes yet to be reported.Systematic review registrationhttps://www.crd.york.ac.uk/prospero, identifier CRD42020193027

Best practice standards for the delivery of NHS infection services in the United Kingdom

Infection expertise in the NHS has historically been provided predominantly by hospital-based medical microbiologists responsible for provision of diagnostic services and advice to front-line clinicians. While most hospitals had consultant-led microbiology departments, infectious iiseases departments were based in a small number of specialist centres. The demand for infection expertise is growing in the NHS, driven by advances in medical care, increasing awareness of the impact of antibiotic resistant and healthcare associated infections and threats from emerging infectious diseases. At the same time diagnostic services are being reorganised into pathology networks. The Combined Infection Training (CIT) is delivering a consultant workforce with expertise both in laboratory diagnostic practice and delivery of direct patient care. These changes create challenges for delivery of high quality infection expertise equitably across the NHS. They also offer an opportunity to shape infection services to meet clinical and laboratory demands.To date there has not been an attempt to bring together a single set of best practice guidelines for the requirements of an infection service. This document sets out seven standards. These are written to be practical and flexible according to the diverse ways in which infection expertise may be required across the NHS. It has been prepared by the Clinical Services Committee of the British Infection Association drawing on published evidence and guidance where they exist and on the group’s extensive experience of delivering infection services in hospitals across the NHS. It was then refined with input from the RCP Joint Specialist committee (JSC) and the RCPath Specialist Advisory Committee (SAC) and through consultation with the RCPath membership. It has been endorsed by the Royal College of Pathologists and the Royal College of Physicians. It will be reviewed annually by the CSC and updated as additional evidence becomes available

Retrospective Analysis of the 2014-2015 Ebola Epidemic in Liberia.

The 2014-2015 Ebola epidemic has been the most protracted and devastating in the history of the disease. To prevent future outbreaks on this scale, it is imperative to understand the reasons that led to eventual disease control. Here, we evaluated the shifts of Ebola dynamics at national and local scales during the epidemic in Liberia. We used a transmission model calibrated to epidemiological data between June 9 and December 31, 2014, to estimate the extent of community and hospital transmission. We found that despite varied local epidemic patterns, community transmission was reduced by 40-80% in all the counties analyzed. Our model suggests that the tapering of the epidemic was achieved through reductions in community transmission, rather than accumulation of immune individuals through asymptomatic infection and unreported cases. Although the times at which this transmission reduction occurred in the majority of the Liberian counties started before any large expansion in hospital capacity and the distribution of home protection kits, it remains difficult to associate the presence of interventions with reductions in Ebola incidence

Harnessing case isolation and ring vaccination to control Ebola.

As a devastating Ebola outbreak in West Africa continues, non-pharmaceutical control measures including contact tracing, quarantine, and case isolation are being implemented. In addition, public health agencies are scaling up efforts to test and deploy candidate vaccines. Given the experimental nature and limited initial supplies of vaccines, a mass vaccination campaign might not be feasible. However, ring vaccination of likely case contacts could provide an effective alternative in distributing the vaccine. To evaluate ring vaccination as a strategy for eliminating Ebola, we developed a pair approximation model of Ebola transmission, parameterized by confirmed incidence data from June 2014 to January 2015 in Liberia and Sierra Leone. Our results suggest that if a combined intervention of case isolation and ring vaccination had been initiated in the early fall of 2014, up to an additional 126 cases in Liberia and 560 cases in Sierra Leone could have been averted beyond case isolation alone. The marginal benefit of ring vaccination is predicted to be greatest in settings where there are more contacts per individual, greater clustering among individuals, when contact tracing has low efficacy or vaccination confers post-exposure protection. In such settings, ring vaccination can avert up to an additional 8% of Ebola cases. Accordingly, ring vaccination is predicted to offer a moderately beneficial supplement to ongoing non-pharmaceutical Ebola control efforts

Cost-effectiveness of next-generation vaccines: The case of pertussis.

Despite steady vaccination coverage rates, pertussis incidence in the United States has continued to rise. This public health challenge has motivated calls for the development of a new vaccine with greater efficacy and duration of protection. Any next-generation vaccine would likely come at a higher cost, and must provide sufficient health benefits beyond those provided by the current vaccine in order to be deemed cost-effective. Using an age-structured transmission model of pertussis, we quantified the health and economic benefits of a next-generation vaccine that would enhance either the efficacy or duration of protection of the childhood series, the duration of the adult booster, or a combination. We developed a metric, the maximum cost-effective price increase (MCPI), to compare the potential value of such improvements. The MCPI estimates the per-dose price increase that would maintain the cost-effectiveness of pertussis vaccination. We evaluated the MCPI across a range of potential single and combined improvements to the pertussis vaccine. As an upper bound, we found that a next-generation vaccine which could achieve perfect efficacy for the childhood series would permit an MCPI of $18 per dose (95$12-$31). Pertussis vaccine improvements that extend the duration of protection to an average of 75 years would allow for an MCPI of$22 per dose for the childhood series (CI: $10-$33) or $12 for the adult booster (CI:$4-$18). Despite the short duration of the adult booster, improvements to the childhood series could be more valuable than improvements to the adult booster. Combining improvements in both efficacy and duration, a childhood series with perfect efficacy and average duration of 75 years would permit an MCPI of$39 per dose, the highest of any scenario evaluated. Our results highlight the utility of the MCPI metric in evaluating potential vaccines or other interventions when prices are unknown

Characterization of New Virulence Factors Involved in the Intracellular Growth and Survival of Burkholderia pseudomallei.

Burkholderia pseudomallei, the causative agent of melioidosis, has complex and poorly understood extracellular and intracellular lifestyles. We used transposon-directed insertion site sequencing (TraDIS) to retrospectively analyze a transposon library that had previously been screened through a BALB/c mouse model to identify genes important for growth and survival in vivo. This allowed us to identify the insertion sites and phenotypes of negatively selected mutants that were previously overlooked due to technical constraints. All 23 unique genes identified in the original screen were confirmed by TraDIS, and an additional 105 mutants with various degrees of attenuation in vivo were identified. Five of the newly identified genes were chosen for further characterization, and clean, unmarked bpsl2248, tex, rpiR, bpsl1728, and bpss1528 deletion mutants were constructed from the wild-type strain K96243. Each of these mutants was tested in vitro and in vivo to confirm their attenuated phenotypes and investigate the nature of the attenuation. Our results confirm that we have identified new genes important to in vivo virulence with roles in different stages of B. pseudomallei pathogenesis, including extracellular and intracellular survival. Of particular interest, deletion of the transcription accessory protein Tex was shown to be highly attenuating, and the tex mutant was capable of providing protective immunity against challenge with wild-type B. pseudomallei, suggesting that the genes identified in our TraDIS screen have the potential to be investigated as live vaccine candidates