The Impact of Covid-19 on Future Higher-Age Mortality

Covid-19 has predominantly affected mortality at high ages. It kills by inflaming and clogging the air sacs in the lungs, depriving the body of oxygen ‒ inducing hypoxia ‒ which closes down essential organs, in particular the heart, kidneys and liver, and causes blood clots (which can lead to stroke or pulmonary embolism) and neurological malfunction. Evidence from different countries points to the fact that people who die from Covid-19 are often, but not always, much less healthy than the average for their age group. This is true for England & Wales – the two countries we focus on in this study. The implication is that the years of life lost through early death are less than the average for each age group, with how much less being a source of considerable debate. We argue that many of those who die from coronavirus would have died anyway in the relatively near future due to their existing frailties or co-morbidities. We demonstrate how to capture this link to poorer-than-average health using a model in which individual deaths are ‘accelerated’ ahead of schedule due to Covid-19. The model structure and its parameterization build on the observation that Covid-19 mortality by age is approximately proportional to all-cause mortality. This, in combination with current predictions of total deaths, results in the important conclusion that, everything else being equal, the impact of Covid-19 on the mortality rates of the surviving population will be very modest. Specifically, the degree of anti-selection is likely to be very small, since the life expectancy of survivors does not increase by a significant amount over pre-pandemic levels. We also analyze the degree to which Covid-19 mortality varies with socio-economic status. Headline statistics suggest that the most deprived groups have been disproportionately affected by Covid-19. However, once we control for regional differences in mortality rates, Covid-19 deaths in both the most and least deprived groups are also proportional to the all-cause mortality of these groups. However, the groups in between have approximately 10-15% lower Covid-19 deaths compared with their all-cause mortality. We argue that useful lessons about the potential pattern of accelerated deaths from Covid-19 can be drawn from examining deaths from respiratory diseases, especially at different age ranges. We also argue that it is possible to draw useful lessons about volatility spikes in Covid-19 deaths from examining past seasonal flu epidemics. However, there is an important difference. Whereas the spikes in seasonal flu increase with age, our finding that Covid-19 death rates are approximately proportional to all-cause mortality suggests that any spike in Covid-19 mortality in percentage terms would be similar across all age ranges. Finally, we discuss some of the indirect consequences for future mortality of the pandemic and the ‘lockdown’ measures governments have imposed to contain it. For example, there is evidence that some surviving patients at all ages who needed intensive care could end up with a new impairment, such as organ damage, which will reduce their life expectancy. There is also evidence that many people in lockdown did not seek a timely medical assessment for a potential new illness, such as cancer, or deferred seeking treatment for an existing serious illness, with the consequence that non-Covid-19-related mortality rates could increase in future. Self-isolation during lockdown has contributed to an increase in alcohol and drug consumption by some people which might, in turn, reduce their life expectancy. If another consequence of the pandemic is a recession and/or an acceleration in job automation, resulting in long-term unemployment, then this could lead to so-called ‘deaths of despair’ in future. Other people, by contrast, might permanently change their social behaviour or seek treatments that delay the impact or onset of age-related diseases, one of the primary factors that make people more susceptible to the virus – both of which could have the effect of increasing their life expectancy. It is, however, too early to quantify these possibilities, although it is conceivable that these indirect consequences could have a bigger impact on future average life expectancy than the direct consequences measured by the accelerated deaths model

Simultaneous multi-frequency single-pulse properties of AXP XTE J1810-197

We have used the 76-m Lovell, 94-m equivalent WSRT and 100-m Effelsberg radio telescopes to investigate the simultaneous single-pulse properties of the radio emitting magnetar AXP XTE J1810-197 at frequencies of 1.4, 4.8 and 8.35 GHz during May and July 2006. We study the magnetar's pulse-energy distributions which are found to be very peculiar as they are changing on time-scales of days and cannot be fit by a single statistical model. The magnetar exhibits strong spiky single giant-pulse-like subpulses, but they do not fit the definition of the giant pulse or giant micropulse phenomena. Measurements of the longitude-resolved modulation index reveal a high degree of intensity fluctuations on day-to-day time-scales and dramatic changes across pulse phase. We find the frequency evolution of the modulation index values differs significantly from what is observed in normal radio pulsars. We find that no regular drifting subpulse phenomenon is present at any of the observed frequencies at any observing epoch. However, we find a quasi-periodicity of the subpulses present in the majority of the observing sessions. A correlation analysis indicates a relationship between components from different frequencies. We discuss the results of our analysis in light of the emission properties of normal radio pulsars and a recently proposed model which takes radio emission from magnetars into consideration.Comment: 15 pages, 11 figures, accepted for publication by MNRA

Phase and Intensity Distributions of Individual Pulses of PSR B0950+08

The distribution of the intensities of individual pulses of PSR B0950+08 as a function of the longitudes at which they appear is analyzed. The flux density of the pulsar at 111 MHz varies strongly from day to day (by up to a factor of 13) due to the passage of the radiation through the interstellar plasma (interstellar scintillation). The intensities of individual pulses can exceed the amplitude of the mean pulse profile, obtained by accumulating 770 pulses, by more than an order of magnitude. The intensity distribution along the mean profile is very different for weak and strong pulses. The differential distribution function for the intensities is a power law with index n = -1.1 +- 0.06 up to peak flux densities for individual pulses of the order of 160 Jy

Statistics of Auroral Langmuir Waves

The Physics of Auroral Zone Electrons II (PHAZE II) sounding rocket was launched in February 1997 into active pre-midnight aurora. The resulting high frequency wave data are dominated by Langmuir waves. Consistent with many previous observations the Langmuir waves are sporadic, occurring in bursts lasting up to a few hundred ms. We compute statistics of the electric field amplitudes of these Langmuir waves, with two results. First, the shape of the distribution of running averages of the electric field amplitudes remains approximately stationary for a large range of widths of running average less than ~0.3 ms and for a large range of widths exceeding about 1 ms. The interpretation of this transition timescale is unclear but appears unlikely to be of instrumental origin. Second, for 2.6-ms running averages, corresponding to the latter range, the distribution of the logarithm of electric field amplitudes matches a Gaussian form very well for all nine cases studied in detail, hence the statistics are lognormal. These distributions are consistent with stochastic growth theory (SGT)

Results from the third Scottish National Prevalence Survey: is a population health approach now needed to prevent healthcare-associated infections?

Summary Background Healthcare associated infections (HAI) are a major public health concern and a significant cause of morbidity and mortality. A robust and current evidence base that is specific to local, national and Europe-wide settings is necessary to inform the development of strategies to reduce HAI and contain antimicrobial resistance (AMR). Aim To measure the prevalence of HAI and antimicrobial prescribing and identify key priority areas for interventions to reduce the burden of infection. Methods A national rolling PPS in National Health Service (NHS) acute, NHS non-acute, NHS paediatric and independent hospitals was carried out between September and November 2016 using the European Centre for Disease Prevention and Control protocol designed for the European PPS. Findings The prevalence of HAI was 4.6%, 2.7% and 3.2% in acute adults, paediatric and non-acute patient groups, respectively. The most common HAI types reported in adult patients were urinary tract infection and pneumonia. The prevalence of antimicrobial prescribing was 35.7%, 29.3% and 13.8% in acute adults, paediatric and non-acute patient groups, respectively. Respiratory, skin and soft tissue, gastrointestinal and urinary tract infections were the most common infections being treated at the time of survey. Conclusion HAI continues to be a public health concern in Scotland. UTI and pneumonia continue to place a significant burden on patients and on healthcare delivery, including those that develop in the community and require hospital admission. A broader population health approach which focuses on reducing the risk of infection upstream would reduce these infections in both community and hospital settings

Anti-shielding Effect and Negative Temperature in Instantaneously Reversed Electric Fields and Left-Handed Media

The connections between the anti-shielding effect, negative absolute temperature and superluminal light propagation in both the instantaneously reversed electric field and the left-handed media are considered in the present paper. The instantaneous inversion of the exterior electric field may cause the electric dipoles into the state of negative absolute temperature and therefore give rise to a negative effective mass term of electromagnetic field (i. e., the electromagnetic field propagating inside the negative-temperature medium will acquire an imaginary rest mass), which is said to result in the potential superluminality effect of light propagation in this anti-shielding dielectric. In left-handed media, such phenomena may also arise.Comment: 9 pages, Late

Dihydroartemisinin-piperaquine versus artesunate-amodiaquine for treatment of malaria infection in pregnancy in Ghana: an open-label, randomized, non-inferiority trial.

To determine whether dihydroartemisinin-piperaquine (DHA-PPQ) is non-inferior to artesunate-amodiaquine (ASAQ) for treating uncomplicated malaria infection in pregnancy. 417 second/ third trimester pregnant women with confirmed asymptomatic Plasmodium falciparum parasitaemia were randomized to receive DHA-PPQ or ASAQ over 3 days. Women were followed up on days 1, 2, 3, 7, 14, 28 and 42 after treatment start and at delivery for parasitological, haematological, birth outcomes and at 6-weeks post-partum to ascertain the health status of the babies. Parasitological efficacy (PE) by days 28 and 42 were co-primary outcomes. Analysis was per-protocol (PP) and modified intention-to-treat (ITT). Non-inferiority was declared if the two-sided 95% confidence interval for PE at the endpoints excluded 5% lower efficacy for DHA-PPQ. Secondary outcomes were assessed for superiority. In PP analysis, PE was 91.6% for DHA-PPQ and 89.3% for ASAQ by day 28 and 89.0% and 86.5% respectively by day 42. DHA-PPQ was non-inferior to ASAQ with respect to uncorrected PE {adjusted difference by day 28 (DHA-PPQ-ASAQ); 3.5% (95%CI: -1.5, 8.5) and day 42: 3.9% (95%CI: -2.7, 10.4)}. ITT analysis gave similar results. PCR to distinguish recrudescence and reinfection was unsuccessful. DHA-PPQ recipients had fewer adverse events of vomiting, dizziness and general weakness compared to ASAQ. Both drugs were well-tolerated and there was no excess of adverse birth outcomes. DHA-PPQ was non-inferior to ASAQ for treatment of malaria infection during pregnancy. No safety concerns were identified. Our findings contribute to growing evidence that DHA-PPQ is useful for control of malaria in pregnancy. This article is protected by copyright. All rights reserved

A comprehensive resource for induced pluripotent stem cells from patients with primary tauopathies

Primary tauopathies are characterized neuropathologically by inclusions containing abnormal forms of the microtubule-associated protein tau (MAPT) and clinically by diverse neuropsychiatric, cognitive, and motor impairments. Autosomal dominant mutations in the MAPT gene cause heterogeneous forms of frontotemporal lobar degeneration with tauopathy (FTLD-Tau). Common and rare variants in the MAPT gene increase the risk for sporadic FTLD-Tau, including progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD). We generated a collection of fibroblasts from 140 MAPT mutation/risk variant carriers, PSP, CBD, and cognitively normal controls; 31 induced pluripotent stem cell (iPSC) lines from MAPT mutation carriers, non-carrier family members, and autopsy-confirmed PSP patients; 33 genome engineered iPSCs that were corrected or mutagenized; and forebrain neural progenitor cells (NPCs). Here, we present a resource of fibroblasts, iPSCs, and NPCs with comprehensive clinical histories that can be accessed by the scientific community for disease modeling and development of novel therapeutics for tauopathies

In Vitro Investigation of a Terbinafine Impregnated Subcutaneous Implant for Veterinary Use

A terbinafine impregnated subcutaneous implant was evaluated to determine if drug was released into isotonic saline over the course of 6 months at two different temperatures, 37°C and 4°C. These temperatures were chosen to simulate the nonhibernating (37°C) and hibernating body (4°C) temperatures of little brown bats (Myotis lucifugus). Insectivorous bats of North America, including little brown bats, have been devastated by white nose syndrome, a fungal infection caused by Geomyces destructans. No treatments exist for bats infected with G. destructans. Implants were placed into isotonic saline; samples were collected once per week and analyzed with HPLC to determine terbinafine concentrations. The mean amount of terbinafine released weekly across the 28 weeks was approximately 1.7 μg at 4°C and 4.3 μg at 37°C. Although significant differences in the amount released did occur at some time points, these differences were not consistently greater or less at either of the temperatures. This study showed that terbinafine was released from an impregnated implant over the course of 6 months at concentrations ranging from 0.02 to 0.06 μg/mL depending on temperature, which may be appropriate for little brown bats (Myotis lucifugus) infected with Geomyces destructans, the etiologic agent of white nose syndrome