Additional file 1 of ‘A system that is struggling’: understanding health protection resilience in England during the COVID-19 pandemic through the experiences of local health protection responders

Additional file 1: S1. GRIPP-2 Reporting

Click-evoked ABR waveforms in control and Tc1 mice.

<p>Averaged ABR waveforms recorded in response to clicks in a wildtype (a) and Tc1 (b) mouse. Waveforms are displayed for stimuli in 3 dB incremental steps from 25 dB SPL at the bottom to 94 dB SPL at the top of each panel. Positive peaks 1–4 (P1–P4) and negative peaks (N1–N4) are indicated by arrows at the top of each panel. The heavy black line indicates the visually-determined threshold; 37 dB SPL in both cases. The scale-bar indicates 10 µV amplitude.</p

ABR Thresholds in control and Tc1 mice.

<p>ABR thresholds for individual control (black circles) and Tc1 (red circles) mice are shown on the left and right panels respectively. The middle panel indicates the mean (± standard deviation, SD) thresholds for control (black) & Tc1 (red) mice, respectively. Tone-evoked ABRs were recorded over the left side of the head only whereas click-evoked ABRs were recorded bilaterally.</p

Genes trisomic in Ts65Dn but disomic in Tc1.

<p>Genes trisomic in Ts65Dn but disomic in Tc1.</p

Cleared Inner Ears from Control and Tc1 mice.

<p>Gross morphology of the inner ears of a control and Tc1 mouse are shown in <b>A</b> and <b>B</b>, respectively. The cochlear duct (C) is visible as a spiral structure towards the top of each image. The oval (O) and round (R) windows can be seen in the middle of each panel. The semicircular canals of each inner ear are found in the wider region at the bottom of each image. No abnormalities can be detected in Tc1 inner ears.</p

Electrical properties of IHCs (P25–P26) and OHCs (P13–P14) from control and Tc1 mice.

<p>Values are means ± SEM; number of cells is in parentheses. <i>C</i>_m = membrane capacitance; <i>V</i>_m = resting membrane potential; g_Leak = resting leak conductance; <i>V</i>_Rev = reversal potential of the total current.</p

Middle Ears of Control and Tc1 mice.

<p><b>A</b> and B, illustrate the malleus (left), incus (middle) and stapes (right), from a wildtype mouse and a Tc1 mouse, respectively, showing no differences. <b>C–F</b> illustrate sections through the mucosal lining of the middle ear (H&E stained) for a wildtype (<b>C</b>, <b>E</b>) and Tc1 (<b>D</b>, <b>F</b>) mouse, showing no sign of any middle ear inflammation.</p

Current recording in OHCs from adult Tc1 mice.

<p><b>A</b> and B, Typical current responses from apical-coil adult control (P14) and Tc1 (P13) OHCs. Currents were elicited by depolarizing voltage steps (10 mV nominal increments) from −124 mV (holding potential of −84 mV). <b>C</b>, Steady-state I–V curves for control (P13–P14, <i>n</i> = 9) and Tc1 (P13–14, <i>n</i> = 3) OHCs. <b>D</b>, Average size of the total K⁺ current at the steady-state (<i>I</i>_K+<i>I</i>_K,n) and the isolated I_K,n.</p

Fluorescence <i>in situ</i> hybridisation characterisation of the structure of the Hsa21 in Tc1 mice.

<p>(<i>a</i>) Hsa21 specific paint (green) c-hybridised with a Hsa13/21 alpha satellite centromere probe (red giving yellow signal). (<i>b</i>) Hsa21 telomere specific probe (green) co-hybridised with an Hsa13/21 alpha satellite centromere probe (red). (<i>c</i>) Human chromosome pan-telomeric probe (red) i.e. hybridises to all human and mouse pan telomere sequences, demonstrating that Hsa21 in the Tc1 is structurally altered and is metacentric.</p

Schematic of the proposed structure of Tc1-Hsa21.

<p>Reference: Ideogram of human chromosome 21, numbers 1–41 indicate regions of Tc1 Hsa21 delineated according to <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0060482#pone.0060482.s010" target="_blank">Table S5</a>. Tc1: rearranged structure of the Hsa21 in Tc1 mice. The order of regions 11, 20, 22, 24, 19, 18, 25, 17, 13, 28, 26, 6, 15, 35, 32, 5, 9, 10, 33, 38, 40, 36, 37, 31, 29, 23, 22, 21, 20, and 11 in this schematic are based on FISH mapping data (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0060482#pone.0060482.s002" target="_blank">Fig. S2</a>). The certainty of the rearrangement is indicated by a red line, solid line more certain, dotted line suggested. Inverted chromosome regions are indicated by the red arrow symbol. Region 12 is triplicated but the position of the other two copies is unknown. Position of region 27 is unknown. The positions of acrocentric regions 1, 2, 3, 7 and 8 are unknown and are placed arbitrarily. Regions 26, 30 and 41 are duplications and their positions are suggested by FISH within the resolution of the technique. Regions 14, 16, 34 and 39 are deleted.</p