Effects on Cancer Prevention from the COVID-19 Pandemic.

The COVID-19 pandemic led to disruption of health services around the world, including cancer services. We carried out a narrative review of the effect of the pandemic on cancer prevention services, including screening. Services were severely affected in the early months of the pandemic, and in some areas are still recovering. Large numbers of additional cancers or additional late-stage cancers have been predicted to arise over the coming years as a result of this disruption. To minimize the effects on cancer outcomes, it is necessary to return as quickly as possible to prepandemic levels of screening and prevention activity or indeed to exceed these levels. The recovery of services should address health inequalities.

Ultrahigh-pressure disordered eight-coordinated phase of Mg2GeO4: Analogue for super-Earth mantles.

Mg2GeO4 is important as an analog for the ultrahigh-pressure behavior of Mg2SiO4, a major component of planetary interiors. In this study, we have investigated magnesium germanate to 275 GPa and over 2,000 K using a laser-heated diamond anvil cell combined with in situ synchrotron X-ray diffraction and density functional theory (DFT) computations. The experimental results are consistent with the formation of a phase with disordered Mg and Ge, in which germanium adopts eightfold coordination with oxygen: the cubic, Th3P4-type structure. DFT computations suggest partial Mg-Ge order, resulting in a tetragonal [Formula: see text] structure indistinguishable from [Formula: see text] Th3P4 in our experiments. If applicable to silicates, the formation of this highly coordinated and intrinsically disordered phase may have important implications for the interior mineralogy of large, rocky extrasolar planets.

Correction: Back et al. A New Micromonospora Strain with Antibiotic Activity Isolated from the Microbiome of a Mid-Atlantic Deep-Sea Sponge. Mar. Drugs 2021, 19, 105.

After publication of this article [...].

Phase transitions beyond post-perovskite in NaMgF3 to 160 GPa.

Neighborite, NaMgF3, is used as a model system for understanding phase transitions in ABX3 systems (e.g., MgSiO3) at high pressures. Here we report diamond anvil cell experiments that identify the following phases in NaMgF3 with compression to 162 GPa: NaMgF3 (perovskite) → NaMgF3 (post-perovskite) → NaMgF3 (Sb2S3-type) → NaF (B2-type) + NaMg2F5 (P2 1 /c) → NaF (B2) + MgF2 (cotunnite-type). Our results demonstrate the existence of an Sb2S3-type post-post-perovskite ABX3 phase. We also experimentally demonstrate the formation of the P2 1 /c AB2X5 phase which has been proposed theoretically to be a common high-pressure phase in ABX3 systems. Our study provides an experimental observation of the full sequence of phase transitions from perovskite to post-perovskite to post-post-perovskite followed by 2-stage breakdown to binary compounds. Notably, a similar sequence of transitions is predicted to occur in MgSiO3 at ultrahigh pressures, where it has implications for the mineralogy and dynamics in the deep interior of large, rocky extrasolar planets.

A New Micromonospora Strain with Antibiotic Activity Isolated from the Microbiome of a Mid-Atlantic Deep-Sea Sponge.

To tackle the growing problem of antibiotic resistance, it is essential to identify new bioactive compounds that are effective against resistant microbes and safe to use. Natural products and their derivatives are, and will continue to be, an important source of these molecules. Sea sponges harbour a diverse microbiome that co-exists with the sponge, and these bacterial communities produce a rich array of bioactive metabolites for protection and resource competition. For these reasons, the sponge microbiota constitutes a potential source of clinically relevant natural products. To date, efforts in bioprospecting for these compounds have focused predominantly on sponge specimens isolated from shallow water, with much still to be learned about samples from the deep sea. Here we report the isolation of a new Micromonospora strain, designated 28ISP2-46T, recovered from the microbiome of a mid-Atlantic deep-sea sponge. Whole-genome sequencing reveals the capacity of this bacterium to produce a diverse array of natural products, including kosinostatin and isoquinocycline B, which exhibit both antibiotic and antitumour properties. Both compounds were isolated from 28ISP2-46T fermentation broths and were found to be effective against a plethora of multidrug-resistant clinical isolates. This study suggests that the marine production of isoquinocyclines may be more widespread than previously supposed and demonstrates the value of targeting the deep-sea sponge microbiome as a source of novel microbial life with exploitable biosynthetic potential.

In situ X-Ray Diffraction of Shock-Compressed Fused Silica.

Because of its widespread applications in materials science and geophysics, SiO_{2} has been extensively examined under shock compression. Both quartz and fused silica transform through a so-called "mixed-phase region" to a dense, low compressibility high-pressure phase. For decades, the nature of this phase has been a subject of debate. Proposed structures include crystalline stishovite, another high-pressure crystalline phase, or a dense amorphous phase. Here we use plate-impact experiments and pulsed synchrotron x-ray diffraction to examine the structure of fused silica shock compressed to 63 GPa. In contrast to recent laser-driven compression experiments, we find that fused silica adopts a dense amorphous structure at 34 GPa and below. When compressed above 34 GPa, fused silica transforms to untextured polycrystalline stishovite. Our results can explain previously ambiguous features of the shock-compression behavior of fused silica and are consistent with recent molecular dynamics simulations. Stishovite grain sizes are estimated to be ∼5-30 nm for compression over a few hundred nanosecond time scale.

Novel Bacterial Topoisomerase Inhibitors with Potent Broad-Spectrum Activity against Drug-Resistant Bacteria.

The novel bacterial topoisomerase inhibitor class is an investigational type of antibacterial inhibitor of DNA gyrase and topoisomerase IV that does not have cross-resistance with the quinolones. Here, we report the evaluation of the in vitro properties of a new series of this type of small molecule. Exemplar compounds selectively and potently inhibited the catalytic activities of Escherichia coli DNA gyrase and topoisomerase IV but did not block the DNA breakage-reunion step. Compounds showed broad-spectrum inhibitory activity against a wide range of Gram-positive and Gram-negative pathogens, including biodefence microorganisms and Mycobacterium tuberculosis No cross-resistance with fluoroquinolone-resistant Staphylococcus aureus and E. coli isolates was observed. Measured MIC90 values were 4 and 8 µg/ml against a panel of contemporary multidrug-resistant isolates of Acinetobacter baumannii and E. coli, respectively. In addition, representative compounds exhibited greater antibacterial potency than the quinolones against obligate anaerobic species. Spontaneous mutation rates were low, with frequencies of resistance typically <10-8 against E. coli and A. baumannii at concentrations equivalent to 4-fold the MIC. Compound-resistant E. coli mutants that were isolated following serial passage were characterized by whole-genome sequencing and carried a single Arg38Leu amino acid substitution in the GyrA subunit of DNA gyrase. Preliminary in vitro safety data indicate that the series shows a promising therapeutic index and potential for low human ether-a-go-go-related gene (hERG) inhibition (50% inhibitory concentration [IC50], >100 µM). In summary, the compounds' distinct mechanism of action relative to the fluoroquinolones, whole-cell potency, low potential for resistance development, and favorable in vitro safety profile warrant their continued investigation as potential broad-spectrum antibacterial agents.

High-Pressure Study of Perovskites and Postperovskites in the (Mg,Fe)GeO3 System.

The effect of incorporation of Fe2+ on the perovskite (Pbnm) and postperovskite (Cmcm) structures was investigated in the (Mg,Fe)GeO3 system at high pressures and temperatures using laser-heated diamond anvil cell and synchrotron X-ray diffraction. Samples with compositions of Mg# ≥ 48 were shown to transform to the perovskite (∼30 GPa and ∼1500 K) and postperovskite (>55 GPa, ∼1600-1800 K) structures. Compositions with Mg# ≥ 78 formed single-phase perovskite and postperovskite, whereas those with Mg# < 78 showed evidence for partial decomposition. The incorporation of Fe into the perovskite structure causes a decrease in octahedral distortion as well as a modest decrease in bulk modulus (K0) and a modest increase in zero-pressure volume (V0). It also leads to a decrease in the perovskite-to-postperovskite phase transition pressure by ∼9.5 GPa over compositions from Mg#78 to Mg#100.

Comparing the effectiveness and cost-effectiveness of text-message reminders and telephone patient navigation to improve the uptake of faecal immunochemical test screening among non-responders in London: a randomised controlled trial protocol.

INTRODUCTION: Participation in bowel cancer screening is lower in regions where there is high ethnic diversity and/or socioeconomic deprivation. Interventions, such as text message reminders and patient navigation (PN), have the potential to increase participation in these areas. As such, there is interest in the comparative effectiveness of these interventions to increase bowel cancer screening participation, as well as their relative cost-effectiveness. METHODS AND ANALYSIS: This study will use a three-arm randomised controlled trial design to compare the effectiveness and cost-effectiveness of text message reminders and PN to increase the uptake of bowel cancer screening in London. Participants will be individuals who have not returned a completed faecal immunochemical test kit within 13 weeks of receiving a routine invitation from the London bowel cancer screening hub. Participants will be randomised (in a 1:1:1 ratio) to receive either (1) usual care (ie, 'no intervention'), (2) a text message reminder at 13 weeks, followed by repeated text message reminders at 15, 17 and 19 weeks (in the event of non-response) or (3) a text message reminder at 13 weeks, followed by PN telephone calls at 15, 17 and 19 weeks in the event of non-response. The primary endpoint will be participation in bowel cancer screening, defined as 'the return of a completed kit by week 24'. Statistical analysis will use multivariate logistic regression and will incorporate pairwise comparisons of all three groups, adjusted for multiple testing. ETHICS AND DISSEMINATION: Approvals to conduct the research have been obtained from University College London's Joint Research Office (Ref: 150666), the Screening Research, Innovation and Development Advisory Committee ('RIDAC', Ref: 2223 014 BCSP Kerrison), the Health Research Authority (Ref: 22/WM/0212) and the Confidentiality Advisory Group (Ref: 22/CAG/0140). Results will be conveyed to stakeholders, notably those managing the screening programme and published in peer-reviewed journals/presented at academic conferences. TRIAL REGISTRATION NUMBER: ISRCTN17245519.

B1-B2 transition in shock-compressed MgO.

Magnesium oxide (MgO) is a major component of the Earth's mantle and is expected to play a similar role in the mantles of large rocky exoplanets. At extreme pressures, MgO transitions from the NaCl B1 crystal structure to a CsCl B2 structure, which may have implications for exoplanetary deep mantle dynamics. In this study, we constrain the phase diagram of MgO with laser-compression along the shock Hugoniot, with simultaneous measurements of crystal structure, density, pressure, and temperature. We identify the B1 to B2 phase transition between 397 and 425 gigapascal (around 9700 kelvin), in agreement with recent theory that accounts for phonon anharmonicity. From 425 to 493 gigapascal, we observe a mixed-phase region of B1 and B2 coexistence. The transformation follows the Watanabe-Tokonami-Morimoto mechanism. Our data are consistent with B2-liquid coexistence above 500 gigapascal and complete melting at 634 gigapascal. This study bridges the gap between previous theoretical and experimental studies, providing insights into the timescale of this phase transition.

Looking is not seeing and listening is not hearing: effect of an intervention to enhance auditory skills of graduate-entry nursing students.

Inspection/observation and listening/auscultation are essential skills for health care providers. Given that observational and auditory skills take time to perfect, there is concern about accelerated students' ability to attain proficiency in a timely manner. This article describes the impact of music auditory training (MAT) for nursing students in an accelerated master's entry program on their competence in detecting heart, lung, and bowel sounds. During the first semester, a two-hour MAT session with focused attention on pitch, timbre, rhythm, and masking was held for the intervention group; a control group received traditional instruction only. Students in the music intervention group demonstrated significant improvement in hearing bowel, heart, and lung sounds (p < .0001). The ability to label normal and abnormal heart sounds doubled; interpretation of normal and abnormal lung sounds improved by 50 percent; and bowel sounds interpretation improved threefold, demonstrating the effect of an adult-oriented, creative, yet practical method for teaching auscultation.

Recovery of the breast screening programme following pandemic-related delays: Should we focus on round length or uptake?

OBJECTIVES: The NHS Breast Screening programme is recovering from the hiatus in screening in 2020 due to the COVID-19 pandemic. Currently, open rather than timed invitations are issued, which leads to lower uptake but more rapid coverage of the eligible population by invitation and therefore closer adherence to a round length of 3 years. We aimed to estimate the likely effect on numbers of cancers detected at incident screens of a range of round lengths and uptake rates. METHODS: We assumed exponential distributions of time to incidence of preclinical screen-detectable cancer and of time to progression thereafter to symptomatic clinical disease. We derived numerical values of these, along with screening sensitivity, from published research results and statistics from the NHS Breast Screening programme. These were used to calculate numbers of cancers detected at incident screens at ages 51-70 by round length and uptake rates. RESULTS: We found that in a homogeneous population of cancers, a 4-year round length with uptake of 62%, as observed with timed appointments in London before the pandemic, would result in 295 cancers screen detected per 10,000 invited, compared to 222 cancers with a 3-year round and uptake of 46%, as observed in London during the recovery period. Similar results were found when we posited two populations, one of rapidly progressing and one of slowly progressing cancers. CONCLUSIONS: It may be more productive in terms of early detection to focus on uptake rather than round length in the programme's recovery from the pandemic.

High pressure phase transition and strength estimate in polycrystalline alumina during laser-driven shock compression.

Alumina (Al2O3) is an important ceramic material notable for its compressive strength and hardness. It represents one of the major oxide components of the Earth's mantle. Static compression experiments have reported evidence for phase transformations from the trigonalα-corundum phase to the orthorhombic Rh2O3(II)-type structure at ∼90 GPa, and then to the post-perovskite structure at ∼130 GPa, but these phases have yet to be directly observed under shock compression. In this work, we describe laser-driven shock compression experiments on polycrystalline alumina conducted at the Matter in Extreme Conditions endstation of the Linac Coherent Light Source. Ultrafast x-ray pulses (50 fs, 1012photons/pulse) were used to probe the atomic-level response at different times during shock propagation and subsequent pressure release. At 107 ± 8 GPa on the Hugoniot, we observe diffraction peaks that match the orthorhombic Rh2O3(II) phase with a density of 5.16 ± 0.03 g cm-3. Upon unloading, the material transforms back to theα-corundum structure. Upon release to ambient pressure, densities are lower than predicted assuming isentropic release, indicating additional lattice expansion due to plastic work heating. Using temperature values calculated from density measurements, we provide an estimate of alumina's strength on release from shock compression.

The Flexner Report--100 years later.

The Flexner Report of 1910 transformed the nature and process of medical education in America with a resulting elimination of proprietary schools and the establishment of the biomedical model as the gold standard of medical training. This transformation occurred in the aftermath of the report, which embraced scientific knowledge and its advancement as the defining ethos of a modern physician. Such an orientation had its origins in the enchantment with German medical education that was spurred by the exposure of American educators and physicians at the turn of the century to the university medical schools of Europe. American medicine profited immeasurably from the scientific advances that this system allowed, but the hyper-rational system of German science created an imbalance in the art and science of medicine. A catching-up is under way to realign the professional commitment of the physician with a revision of medical education to achieve that purpose.

Structural response of α-quartz under plate-impact shock compression.

Because of its far-reaching applications in geophysics and materials science, quartz has been one of the most extensively examined materials under dynamic compression. Despite 50 years of active research, questions remain concerning the structure and transformation of SiO2 under shock compression. Continuum gas-gun studies have established that under shock loading quartz transforms through an assumed mixed-phase region to a dense high-pressure phase. While it has often been assumed that this high-pressure phase corresponds to the stishovite structure observed in static experiments, there have been no crystal structure data confirming this. In this study, we use gas-gun shock compression coupled with in situ synchrotron x-ray diffraction to interrogate the crystal structure of shock-compressed α-quartz up to 65 GPa. Our results reveal that α-quartz undergoes a phase transformation to a disordered metastable phase as opposed to crystalline stishovite or an amorphous structure, challenging long-standing assumptions about the dynamic response of this fundamental material.

Portraits of an illness.

Access to patients' inner lives can be expanded and enriched by incorporating the arts and humanities into the clinical encounter. A series of self-portraits created by an artist undergoing induction chemotherapy for leukemia afforded a unique opportunity to concentrate one's gaze upon the patient as a stimulus for reflection on suffering and isolation of patients. Poetry and theater were also invaluable in expanding the physician's awareness of the shared experience of illness. The process highlights the central role of the "New Humanities" in modern medicine, where science informs the arts and the arts inform science and medicine.

Guidelines for safe surgery in patients with systemic mastocytosis.

Systemic mastocytosis (SM) is a rare disorder with important perioperative implications. The physiological stress of operative procedures and a variety of anesthetic and analgesic medications can be triggers of acute exacerbation of this condition. We present two patients with systemic mastocytosis. One underwent open left inguinal hernia and umbilical hernia repair and the other laparoscopic ventral hernia repair. The literature for perioperative management of patients with SM is extensively reviewed. Both patients were treated preoperatively with intravenous antihistamines and steroids to minimize SM reactions. The first patient underwent uneventful open left inguinal hernia repair and umbilical hernia repair under spinal anesthesia. The second patient underwent general anesthesia. A composite mesh was used to repair a 9 x 12-cm Swiss cheese incisional hernia at the site of previous surgery. After the administration of neostigmine and glycopyrrolate, she developed a generalized rash without any hemodynamic instability. The patient was treated with intravenous Solu-Medrol and Benadryl and was extubated successfully and had an unremarkable postoperative course. Patients with SM require careful perioperative management for surgery under spinal and general anesthesia. These patients can undergo surgical procedures safely and effectively without compromising the standard of care.