Modelling testing and response strategies for COVID-19 outbreaks in remote Australian Aboriginal communities

Background: Remote Australian Aboriginal and Torres Strait Islander communities have potential to be severely impacted by COVID-19, with multiple factors predisposing to increased transmission and disease severity. Our modelling aims to inform optimal public health responses. Methods: An individual-based simulation model represented SARS-CoV2 transmission in communities ranging from 100 to 3500 people, comprised of large, interconnected households. A range of strategies for case finding, quarantining of contacts, testing, and lockdown were examined, following the silent introduction of a case. Results: Multiple secondary infections are likely present by the time the first case is identified. Quarantine of close contacts, defined by extended household membership, can reduce peak infection prevalence from 60 to 70% to around 10%, but subsequent waves may occur when community mixing resumes. Exit testing significantly reduces ongoing transmission. Concurrent lockdown of non-quarantined households for 14 days is highly effective for epidemic control and reduces overall testing requirements; peak prevalence of the initial outbreak can be constrained to less than 5%, and the final community attack rate to less than 10% in modelled scenarios. Lockdown also mitigates the effect of a delay in the initial response. Compliance with lockdown must be at least 80–90%, however, or epidemic control will be lost. Conclusions: A SARS-CoV-2 outbreak will spread rapidly in remote communities. Prompt case detection with quarantining of extended-household contacts and a 14 day lockdown for all other residents, combined with exit testing for all, is the most effective strategy for rapid containment. Compliance is crucial, underscoring the need for community supported, culturally sensitive responses

Examination of Parental Effect on the Progeny Diapause by Reciprocal Cross Test in the Cabbage Beetle, Colaphellus bowringi

The cabbage beetle, Colaphellus bowringi Baly (Coleoptera: Chrysomelidae), a serious pest of crucifers in China, undergoes summer or winter diapause in the soil as an adult. In the present study, the incidence of diapause were measured in reciprocal crosses between a high—diapause strain (HD strain) and a laboratory—selected nondiapausing strain (ND strain) under different photoperiods and temperatures, to explore parental influences on the progeny diapause. Sensitivity to photoperiod in the selected nondiapausing strain was nearly eliminated at 25 °C, whereas sensitivity to temperature of the selected nondiapausing strain was retained under continuous darkness at 20 and 22 °C. Reciprocal crosses between the HD strain and the ND strain showed that the incidence of diapause in the progeny was always intermediate to that of the parents under different photoperiods and temperatures, suggesting that diapause induction was determined by both female and male parents. There was a significant effect of temperature; temperature interacted with reciprocal cross on diapause induction, whereas no significant effect of reciprocal cross was demonstrated. The incidence of diapause in ♀ND × ♂HD was the same as in ♀HD × ♂ND under continuous darkness at 18 °C (100%) and 26 °C (0%), but the former was higher than that in ♀HD × ♂ND under continuous darkness at 22 °C, suggesting that female parent does not exhibit strong influence on the diapause response to temperature. There was a significant effect of photoperiod and reciprocal cross on diapause induction, whereas no significant interactive effect on diapause induction was demonstrated. Incidence of diapause in ♀HD × ♂ND was always higher than in ♀ND × ♂HD at 25 °C and 12:12 L:D, 14:10 L:D, and 16:8 L:D, suggesting a strong maternal influence on the diapause response to photoperiod, though a significant difference was observed only at 14:10 L:D. Our results support the idea that diapause induction is determined by both female and male parents. However, results also indicated that a strong maternal influence on diapause was exhibited only in response to photoperiod

On General BCJ Relation at One-loop Level in Yang-Mills Theory

BCJ relation reveals a dual between color structures and kinematic structure and can be used to reduce the number of independent color-ordered amplitudes at tree level. Refer to the loop-level in Yang-Mills theory, we investigate the similar BCJ relation in this paper. Four-point 1-loop example in N = 4 SYM can hint about the relation of integrands. Five-point example implies that the general formula can be proven by unitary- cut method. We will then prove a 'general' BCJ relation for 1-loop integrands by D-dimension unitary cut, which can be regarded as a non-trivial generalization of the (fundamental)BCJ relation given by Boels and Isermann in [arXiv:1109.5888 [hep-th]] and [arXiv:1110.4462 [hep-th]].Comment: 18 pages, 6 figure

Transient bilateral abducens neuropathy with post-tetanic facilitation and acute hypokalemia associated with oxaliplatin: a case report

<p>Abstract</p> <p>Introduction</p> <p>Oxaliplatin is a cytotoxic platinum compound that is in widespread use in the treatment of gastrointestinal cancers. It has been occasionally associated with acute motor neuropathy, but the precise mechanism is uncertain. To the best of our knowledge, we report the first case of a patient demonstrating post-tetanic facilitation in the setting of transient bilateral abducens neuropathy and hypokalemia, after being infused with oxaliplatin.</p> <p>Case presentation</p> <p>A 47-year-old Indian woman with metastatic gastric cancer was receiving an oxaliplatin infusion at the initiation of her third cycle of palliative chemotherapy. She developed acute bilateral abducens neuropathy with post-tetanic facilitation alongside acute laryngopharyngodysesthesia and hypokalemia. Following supportive management, including potassium infusion and warming, her neurological signs and symptoms were spontaneously resolved. This syndrome did not recur in subsequent cycles following prolongation of infusion duration and the addition of supportive calcium and magnesium infusions.</p> <p>Conclusion</p> <p>The novel clinical observation of post-tetanic facilitation highlights a possible involvement of voltage-gated channels at the presynaptic terminals in the mechanism of acute oxaliplatin neurotoxicity.</p

Treatment of Late Stage Disease in a Model of Arenaviral Hemorrhagic Fever: T-705 Efficacy and Reduced Toxicity Suggests an Alternative to Ribavirin

A growing number of arenaviruses are known to cause viral hemorrhagic fever (HF), a severe and life-threatening syndrome characterized by fever, malaise, and increased vascular permeability. Ribavirin, the only licensed antiviral indicated for the treatment of certain arenaviral HFs, has had mixed success and significant toxicity. Since severe arenaviral infections initially do not present with distinguishing symptoms and are difficult to clinically diagnose at early stages, it is of utmost importance to identify antiviral therapies effective at later stages of infection. We have previously reported that T-705, a substituted pyrazine derivative currently under development as an anti-influenza drug, is highly active in hamsters infected with Pichinde virus when the drug is administered orally early during the course of infection. Here we demonstrate that T-705 offers significant protection against this lethal arenaviral infection in hamsters when treatment is begun after the animals are ill and the day before the animals begin to succumb to disease. Importantly, this coincides with the time when peak viral loads are present in most organs and considerable tissue damage is evident. We also show that T-705 is as effective as, and less toxic than, ribavirin, as infected T-705-treated hamsters on average maintain their weight better and recover more rapidly than animals treated with ribavirin. Further, there was no added benefit to combination therapy with T-705 and ribavirin. Finally, pharmacokinetic data indicate that plasma T-705 levels following oral administration are markedly reduced during the latter stages of disease, and may contribute to the reduced efficacy seen when treatment is withheld until day 7 of infection. Our findings support further pre-clinical development of T-705 for the treatment of severe arenaviral infections

Costs of screening children for hearing disorders and delivery of hearing aids in China

Contains fulltext : 79593.pdf (publisher's version ) (Open Access)BACKGROUND: The burden of disease of hearing disorders among children is high, but a large part goes undetected. School-based screening programs in combination with the delivery of hearing aids can alleviate this situation, but the costs of such programs are unknown. AIM: To evaluate the costs of a school-based screening program for hearing disorders, among approximately 216,000 school children, and the delivery of hearing aids to 206 children at three different care levels in China. METHODS: In a prospective study design, screening and hearing aid delivery costs were estimated on the basis of program records and an empirical assessment of health personnel time input. Household costs for seeking and undergoing hearing health care were collected with a questionnaire, administered to the parents of the child. Data were collected at three study sites representing primary, secondary and tertiary care levels. RESULTS: Total screening and hearing aid delivery costs ranged between RMB70,000 (US$9,000) and RMB133,000 (US$17,000) in the three study sites. Health care cost per child fitted ranged from RMB5,900 (US$760) at the primary care level, RMB7,200 (US$940) at the secondary care level, to RMB8,600 (US$1,120) at the tertiary care level. Household costs were only a small fraction of the overall costs. Cost per child fitted ranged between RMB1,608 and RMB2,812 (US$209-US$365), depending on perspective of analysis and study site. The program was always least costly in the primary care setting. CONCLUSION: Hearing screening and the delivery of hearing aids in China is least costly in a primary care setting. Important questions remain concerning its implementation

Acupuncture for the treatment of severe acute pain in Herpes Zoster: results of a nested, open-label, randomized trial in the VZV Pain Study

<p>Abstract</p> <p>Background</p> <p>Data on the potential efficacy of acupuncture (AC) in controlling intense or very intense pain in patients with Herpes Zoster (HZ) has not been so far adequately assessed in comparison with standard pharmacological treatment (ST) by a controlled trial design.</p> <p>Methods</p> <p>Within the VZV Pescara study, pain was assessed in HZ patients on a Visual Analogue Scale (VAS) and by the McGill Pain Questionnaire (MPQ) both at the beginning and at the end of treatment. Response rates, mean changes in pain intensity, differences in total pain burden with an area-under-the-curve (AUC) method over a 1-year follow-up and differences in the incidence of Post-Herpetic Neuralgia (PHN) were evaluated.</p> <p>Results</p> <p>One hundred and two patients were randomized to receive either AC (n = 52) or ST (n = 50) for 4 weeks. Groups were comparable regarding age, sex, pain intensity at presentation and missed antiviral prescription. Both interventions were largely effective. No significant differences were observed in response rates (81.6% vs 89.2%, p = 0.8), mean reduction of VAS (4.1 +/- 2.3 vs 4.9 +/- 1.9, p = 0.12) and MPQ scores (1.3 +/- 0.9 vs 1.3 +/- 0.9, p = 0.9), incidence of PHN after 3 months (48.4% vs 46.8%, p = 0.5), and mean AUC during follow-up (199 +/- 136 vs 173 +/- 141, p = 0.4). No serious treatment-related adverse event was observed in both groups.</p> <p>Conclusions</p> <p>This controlled and randomized trial provides the first evidence of a potential role of AC for the treatment of acute herpetic pain.</p> <p>Trial registration</p> <p>ChiCTR-TRC-10001146.</p

The Formation and Evolution of the First Massive Black Holes

The first massive astrophysical black holes likely formed at high redshifts (z>10) at the centers of low mass (~10^6 Msun) dark matter concentrations. These black holes grow by mergers and gas accretion, evolve into the population of bright quasars observed at lower redshifts, and eventually leave the supermassive black hole remnants that are ubiquitous at the centers of galaxies in the nearby universe. The astrophysical processes responsible for the formation of the earliest seed black holes are poorly understood. The purpose of this review is threefold: (1) to describe theoretical expectations for the formation and growth of the earliest black holes within the general paradigm of hierarchical cold dark matter cosmologies, (2) to summarize several relevant recent observations that have implications for the formation of the earliest black holes, and (3) to look into the future and assess the power of forthcoming observations to probe the physics of the first active galactic nuclei.Comment: 39 pages, review for "Supermassive Black Holes in the Distant Universe", Ed. A. J. Barger, Kluwer Academic Publisher

A Novel Peptide ELISA for Universal Detection of Antibodies to Human H5N1 Influenza Viruses

BACKGROUND: Active serologic surveillance of H5N1 highly pathogenic avian influenza (HPAI) virus in humans and poultry is critical to control this disease. However, the need for a robust, sensitive and specific serologic test for the rapid detection of antibodies to H5N1 viruses has not been met. METHODOLOGY/PRINCIPAL FINDINGS: Previously, we reported a universal epitope (CNTKCQTP) in H5 hemagglutinin (HA) that is 100% conserved in H5N1 human isolates and 96.9% in avian isolates. Here, we describe a peptide ELISA to detect antibodies to H5N1 virus by using synthetic peptide that comprises the amino acid sequence of this highly conserved and antigenic epitope as the capture antigen. The sensitivity and specificity of the peptide ELISA were evaluated using experimental chicken antisera to H5N1 viruses from divergent clades and other subtype influenza viruses, as well as human serum samples from patients infected with H5N1 or seasonal influenza viruses. The peptide ELISA results were compared with hemagglutinin inhibition (HI), and immunofluorescence assay and immunodot blot that utilize recombinant HA1 as the capture antigen. The peptide ELISA detected antibodies to H5N1 in immunized animals or convalescent human sera whereas some degree of cross-reactivity was observed in HI, immunofluorescence assay and immunodot blot. Antibodies to other influenza subtypes tested negative in the peptide-ELISA. CONCLUSION/SIGNIFICANCE: The peptide-ELISA based on the highly conserved and antigenic H5 epitope (CNTKCQTP) provides sensitive and highly specific detection of antibodies to H5N1 influenza viruses. This study highlighted the use of synthetic peptide as a capture antigen in rapid detection of antibodies to H5N1 in human and animal sera that is robust, simple and cost effective and is particularly beneficial for developing countries and rural areas