Background: Nipocalimab is a human IgG1 monoclonal antibody targeting FcRn that selectively reduces IgG levels without impacting antigen presentation, T- and B-cell functions. This study describes the effect of nipocalimab on vaccine response. Methods: Open-label, parallel, interventional study randomized participants 1:1 to receive intravenous 30mg/kg nipocalimab at Week0 and 15mg/kg at Week2 and Week4 (active) or no drug (control). On Day 3, participants received Tdap and PPSV®23 vaccinations and were followed through Wk16. Results: Twenty-nine participants completed the study and are included (active, n=15; control, n=14). Participants with a positive anti-tetanus IgG response was comparable between groups at Wk2 and Wk16, but lower at Wk4 (nipocalimab 3/15 [20%] vs control 7/14 [50%]; P=0.089). All maintained anti-tetanus IgG above the protective threshold (0.16IU/mL) through Wk16. While anti-pneumococcal-capsular-polysaccharide (PCP) IgG levels were lower during nipocalimab treatment, the percent increase from baseline at Wk2 and Wk16 was comparable between groups. Post-vaccination, anti-PCP IgG remained above 50mg/L and showed a 2-fold increase from baseline throughout the study in both groups. Nipocalimab co-administration with vaccines was safe and well-tolerated. Conclusions: These findings suggest that nipocalimab does not impact the development of an adequate IgG response to T-cell–dependent/independent vaccines and that nipocalimab-treated patients can follow recommended vaccination schedules.

Of 313 patients whose outpatient parenteral antimicrobial therapy was managed by an ID physician, only 39 [12.5%, 95% CI (8.8%–16.1%)] had clinical decisions influenced by erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), or both. ESR/CRP ordering was associated with $530 in excess cost per treatment course (average duration 5.1 weeks) representing a diagnostic stewardship opportunity.

Highly portable and accessible MRI technology will allow researchers to conduct field-based MRI research in community settings. Previous guidance for researchers working with fixed MRI does not address the novel ethical, legal, and societal issues (ELSI) of portable MRI (pMRI). Our interdisciplinary Working Group (WG) previously identified 15 core ELSI challenges associated with pMRI research and recommended solutions. In this article, we distill those detailed recommendations into a Portable MRI Research ELSI Checklist that offers practical operational guidance for researchers contemplating using this technology.

The influence of geomorphological site characteristics on soil clay mineral stability of montmorillonite-containing horizons of a southern Wisconsin soil catena was interpreted in terms of the solute activity function values of pSi(OH)4, pH-1/2pMg2+ and pH-1/3pAl3+ in suspensions of the separated clay fractions. Montmorillonite stability and/or formation vs that of kaolinite for the soil clays was evaluated by a plot of the solute activity functions on a three dimensional diagram derived for montmorillonite, kaolinite, and gibbsite at constant temperature (25°C) and constant pressure (one atm.). Although all the soil clays contained both montmorillonite and kaolinite, the position of the soil clay solute activity functions in the stability diagram clearly reflected the influence of the geomorphological—geochemical site conditions in which each soil horizon was developed, with corresponding differences in the SiO2/Al2O3 molar ratio of the reactive fraction. Montmorillonite stability positions of the solute activity functions were induced by soils (clays with reactive fractions with SiO2/Al2O3 molar ratios = 3–4) from calcareous or poorly drained horizons, while kaolinite stability positions of the functions were induced by soils (clays with reactive fractions of SiO2/Al2O3 molar ratios = 2) from acid, freely drained horizons.

Titanium in TiO2 minerals was differentiated from that isomorphously substituted into minerals by the use of dihydrogen hexafluorotitanate (hydrofluotitanic acid, H2TiF6), which selectively dissolved minerals containing substituted Ti4+, leaving free crystalline TiO2 minerals in the residue. Titanium analyses on the original samples and the residues remaining after H2TiF6 treatment, by both wet chemical (Tiron) and neutron activation methods, indicated that an average of 86 per cent of the titanium in seven kaolinite samples was present in the residual TiO2 form (largely anatase), whereas only 28 per cent in two bentonites was present in the TiO2 form. Residual Ti accounted for 100 per cent of the Ti in synthetic anatase and for 92 per cent of the Ti in coarse clay sized rutile, the latter value suggesting that about 8 per cent amorphous TiO2 was removed from the mechanically dry ground rutile by the H2TiF6 reagent. The Ti present as residual TiO2 in a variety of other samples ranged from 0 to 100 per cent.

A steady state reaction of apparent equilibrium of K mica + Ca2+ ⇄ Ca vermiculite + K+ was indicated by prolonged dissolution extractions from Blount soil clay (from northern Indiana) abundant in dioctahedral mica and vermiculite, with log Keq = 2.92 for the reaction when extrapolated to infinite time. From this and published free energies of formation of mica and kaolinite, a mineral phase stability diagram depicting the phase joins of Ca vermiculite, muscovite, and kaolinite was constructed with the solute activity functions pH-pK+, 2pH-pCa2+, and pSi(OH)4. These solute functions for 14-day reactions of calcareous (and dolomitic), poorly drained Harps soil (from central Iowa) fell near the calcite-dolomite-CO2-H2O phase join, suggesting equilibrium. These functions for Harps soil and the control minerals muscovite, biotite, and (or) vermiculite plus calcite were plotted on the mica-vermiculite stability diagram for various CO2 partial pressures. The points fell on the vermiculite-stable side of the mica-vermiculite plane at CO2 partial pressures of 0.15 and 0.20 atm (similar to soil air that would exist under frozen soil during winter and early spring; 2pH-pCa2+ ≃ 10.3). They fell on the muscovite-stable side of the muscovite-vermiculite plane at CO2 partial pressures of 0.0001 and 0.001 atm (similar to soil air under natural summer conditions; 2pH-pCa2+, 13.6 and 12.6, respectively) and therefore K+ (and 137Cs+ in rainfall) would be expected to be fixed.

The 2pH-pMg2+ values determined for Harps soil at the various CO2 partial pressures plotted either in the Mg montmorillonite stability field or on the Mg-montmorillonite-kaolinite phase join, in concordance with the abundance of montmorillonite and some kaolinite in the medium and fine clay fractions. The solute values for the nearby Clarion soil (upland, noncalcareous) plotted on the montmorillonite-kaolinite join, or with higher CO2 partial pressure, in the kaolinite stability area. The Gibbs free energy of formation (△Gf0) for a dioctahedral Ca vermiculite of −1303.7 kcal per 010 was determined from the Keq. The solute functions for the Blount soil showed kaolinite to be the thermodynamically stable phase with respect to dioctahedral mica and (or) vermiculite. The 14-day solute values for the Harps and upland Clarion soils were also on the kaolinite stability side of the kaolinite-vermiculite join. The kinetics of kaolinite formation in the upper midwestern U.S.A. are apparently slow on a scale of ~ 104 years.

The layer structure of kaolinite from Twiggs, Georgia and fire-clay type kaolinite (Frantex B, from France), particle size separates 2–0·2 μm was studied by high resolution electron microscopy after embedment in Spurr low-viscosity Epoxy media and thin sectioning normal to the (001) planes by an ultramicrotome. Images of the (001) planes (viewed edge-on) of both kaolinites were spaced at 7 Å and generally aligned in parallel, with occasional bending into more widely spaced images of about 10 Å interval. Some of the 10 Å images converged to 7 Å at one or both ends, forming ellipse-shaped islands 80 to 130 Å thick and 300 to 500 Å long. The island areas and interleaved 10 Å layers between 7 Å layers may represent a residue of incomplete weathering of mica to kaolinite.

The proportions of micaccous occlusions were too small and the layer sequences too irregular to be detected by X-ray diffraction. The lateral continuity of the layers through the 7-10-7 Å sequence in a kaolinite particle would partially interrupt or prevent expansion in dimethyl sulfoxide (DMSO) and other kaolinite intercalating media. Discrete mica particles were also observed with parallel images at 10 Å, as impurities in both kaolinites. The small K content of the chemical analyses of the kaolinite samples is accounted for as interlayer K, not only in discrete mica particles but also in the micaceous occlusions.

Four Na2S2O4-reduced Na-vermiculites, each with some trioctahedral mica interstratified, were oxidized with H2O2 at pH 6·5 and again reduced with Na2S2O4 in suspensions at pH 7·5–8·0. The layer charge (CEC + K+), measured at pH 6·50, did not change significantly when octahedral Fe was oxidized (7–92 mmole 100g−1) or reduced (6–71 mmole 100 g−1). Electroneutrality was maintained within the octahedral sheet when Fe was oxidized or reduced. When Fe(II) was oxidized, electroneutrality was maintained by deprotonation of octahedral OH− groups,

(a)

${\left\{{\left[Fe\left(II\right)\right]}_{2}M{g}_4{O}_4{\left(OH\right)}_4\right\}}^{\pm 0}\leftrightarrows {\left\{{\left[Fe\left(III\right)\right]}_{2}M{g}_4{O}_4{\left(OH\right)}_2{O}_2^{\ast }\right\}}^{\pm 0}+2e^{-}+2H^{+}$${\left\{ {{{\left[ {Fe\left( {II} \right)} \right]}_2}M{g_4}{O_4}{{\left( {OH} \right)}_4}} \right\}^{ \pm 0}}\leftrightarrows{\left\{ {{{\left[ {Fe\left( {III} \right)} \right]}_2}M{g_4}{O_4}{{\left( {OH} \right)}_2}O_2^*} \right\}^ {\pm 0}} + 2{e^ - } + 2{H^ + }$

and by ejection of (dissolution of structural) octahedral metallic cations,

(b)

${\left\{{\left[Fe\left(II\right)\right]}_{5}Mg{O}_4{\left(OH\right)}_4\right\}}^{\pm 0}\to {\left\{{\left[Fe\left(III\right)\right]}_4{O}_4{\left(OH\right)}_4\right\}}^{\pm 0}+5e^{-}+F{e}^{3+}+M{g}^{2+}.$${\left\{ {{{\left[ {Fe\left( {II} \right)} \right]}_5}Mg{O_4}{{\left( {OH} \right)}_4}} \right\}^{ \pm 0}} \rightarrow {\left\{ {{{\left[ {Fe\left( {III} \right)} \right]}_4}{O_4}{{\left( {OH} \right)}_4}} \right\}^{ \pm 0}} + 5{e^ - } + F{e^{3 + }} + M{g^{2 + }}.$

When Fe(III) was reduced, electroneutrality was maintained by reprotonation of the deprotonated sites (O*, equation a). Reaction (b) was not reversible. Thus, reversibility of the reaction, Fe(II) ⇄ Fe(III) within the octahedral sheet decreased with increasing amount of ejected metallic cations. The amount of Fe(III) and Mg2+ ejected per Fe(II) oxidized was related to the degree of vermiculitization, being greatest with Na-degraded biotite [0·03 Fe3+ and 0·11 Mg2+ per Fe(II) oxidized] and lowest (nearly zero) with South African vermiculite. The number of deprotonated (O*) and reversible sites increased from 0·69 per Fe(II) oxidized with the K-depleted biotite to approximately 1·0 with South African vermiculite. The weathering increment was small since, of the total amount of Fe + Mg, less than 1·3 per cent was ejected from any of the four vermiculitic materials. When biotite was K-depleted, about 20 m-equiv of layer charge per 100g (300°C basis) was lost, while 51 mmole of Fe(II) per 100g was oxidized in the presence of Na2S2O4 and 82 mmoles in its absence in the aqueous suspensions. Since sequential reduction-oxidation-reduction treatments of K-depleted biotite and mica-containing vermiculites did not cause significant changes in layer charge (r2 = 0·04), the layer charge changes were concluded to be entirely independent of the oxidation or reduction of Fe in these minerals.

Deferration by reduction of free Fe2O3 with Na2S2O4 in the presence of Na citrate and NaHCO3 caused a change in valence state of 10 to 35 per cent of the total structural iron in micaceous vermiculites, soils, nontronite, and muscovite. An increase in Fe2+ on deferration was accompanied by an equivalent decrease in Fe3+. Subsequent treatment with H2O2 reoxidized the structural Fe2+ previously formed.

Sesquioxide coatings on micaceous vermiculites were examined electron microscopically. These coatings were composed predominantly of Fe2O3 with approximately 10 per cent by weight of Al2O3 and small amounts of SiO2, as determined by chemical analysis of the deferration extracts.

The cation exchange capacity (CEC) increased 10–60 per cent as a result of deferration of micaceous vermiculites and soils. Treatment of the deferrated sample with H2O2 restored the Fe3+ content to approximately the original value but the CEC was not affected. Consequently, the increase in CEC on deferration was attributed to the removal of the positively charged sesquioxide coating. The reversible change in valence of structural iron without an equivalent change in CEC was attributed to deprotonation-protonation of the structure (OH− ⇄ O2−) simultaneous with the oxidation-reduction of iron (Fe2+ ⇄ Fe3+) in the phyllosilicate layer.

Mafic chlorite from Benton, Arkansas was comminuted by rotary blending of a suspension, and the — 2 μm fraction separated by sedimentation in H2O. Droplets of suspension of the < 2 μm fraction were dried on a layer of Epoxy resin and then additional Epoxy was added and heat-cured at 48°C to form a resin sandwich. Cross-sections of 600–900 Å thickness were cut on a Reichert automated ultramicrotome. The sections were collected on standard electron microscope specimen screens, reinforced by vacuum evaporated C and examined by transmission electron microscopy (TEM). The Phillips EM 200 electron microscope was equipped with a “microgun” source to minimize heating of the specimen and to improve contrast and high resolution (HREM). Images of the (001) chlorite crystallographic planes spaced at 13·9Å intervals were visible on many of the particle sections. Imaging of the planes depended upon their being nearly parallel to the electron beam (within 0° 10’) and therefore, many particles which had other orientations did not show the 13·9Å image. Micrographs made before appreciable irradiation by the electron beam revealed images of fringes corresponding to the 7·22Å (002) spacing of chlorite. Loss of the 7·22 Å fringes and reinforcement of those at 13·9 A resulted from heating of the chlorite in the electron beam. This behavior is analogous to the well-known crystallographic effects of heating chlorite at 550–760°C.

Scanning electron microscopic (SEM) examination of the quartz isolated from chert of Transvaal and Swaziland, of 2000 and 3400 million year (MY) ages, respectively, in southern Africa revealed marked differences in quartz morphology. Well-defined individual euhedral quartz crystals, with polyhedral triple-point faces, were clearly evident on freshly fractured Transvaal chert surfaces as well as with the quartz isolates from the chert. The morphology and coarseness suggest crystal growth with little, if any, metamorphism; however, the δ18O values of 23.8–24.1‰ suggest crystallization temperatures of perhaps 40–45°C. In contrast, fracture surfaces of the older, strongly metamorphosed Swaziland cherts revealed a high degree of grain intergrowth which inhibited fracture between quartz grains. Quartz isolates from these showed strongly interlocked quartz crystal clusters and elongated chips of quartz with poorly defined irregular faces. Intercalation of mineral veins in the cherts on a mm scale and the intergrown character of the quartz grain boundaries provide evidence that the latter cherts have been strongly metamorphosed and recrystallized, in keeping with 14.6–15.1‰ δ18O values, corresponding to 80°C fractionation with water. The SEM micrographs of the fine quartz (1–10 µm) isolated from the Otavi dolomite formation of the 700-MY Damara System and from the 2000-MY Transvaal Dolomite Series revealed well-defined subhedral and euhedral quartz crystals of small size which, together with the 26.9–27.8‰ and 23.8‰ δ18O values, respectively, indicate that these dolomites have been affected little, if any, by post-depositional metamorphism; their crystallization temperatures fall in the range of 25–30 and 40–45°C, respectively.

Three kinds of opal-cristobalite, differentiated by the sharpness of the 4·1 Å XRD peak, were isolated from the Helms (Texas) bentonite by selective chemical dissolution followed by specific gravity separation. The δ18O value (oxygen isotope abundance) for these cristobalite isolates ranged from approximately 26–30‰ (parts per thousand), increasing with increased breadth of the 4·1 Å XRD peak. Opal-cristobalite isolated from the Monterey diatomite had a δ18O value of 34‰. These δ18O values are in the range for Cretaceous cherts (approximately 32‰) and are unlike the values of 9–11‰ obtained for low-cristobalite (XRD peaks at 4·05, 3·13, 2·4, and 2·49) formed hydrothermally or isolated from the vesicles of obsidian. The morphology pseudomorphic after diatoms, observed with the scanning electron microscope, was more apparent in the opal-cristobalite from the Monterey diatomite of Miocene age (approximately 10 million yr old) than in the spongy textured opal-cristobalite from the Helms bentonite, reflecting the 40 million yr available for crystallization since Upper Eocene.

The oxygen isotope abundance of Helms montmorillonite (δ18O = 26‰) indicates that it was formed in sea water while the δ18O values of the associated opal-cristobalite indicate that this SiO2 polymorph probably formed at approximately 25°C in meteoric water. Although both cristobalite and mont-montmorillonite in the bentonite were authigenic, the crystallization of the SiO2 phase apparently required a considerably longer period and occurred mainly after tectonic uplift.

In contrast to the results for cristobalite, quartz from the Helms and Upton (Wyoming) bentonites had δ18O values of 15 and 21‰ respectively. Such intermediate values, similar to those of aerosolic dusts of the Northern Hemisphere, loess, and many fluvial sediments and shales of the North Central United States (U.S.A.), preclude either a completely authigenic or a completely igneous origin for the quartz. These values probably result from a mixing of quartz from high and low temperature sources, detritally added to the ash or bentonite bed.

From 2 to 28% opal-cristobalite was isolated from the 2–20 µm fraction of rhyolitic and andesitic tuffaceous pyroclastics from the Island of Honshu, Japan, where it had been formed in hydrothermal springs at temperatures of ∼25–170°C as calculated from the oxygen isotopic ratios (18O/16O). Three of the isolates gave X-ray powder diffractograms with strong peaks at 4.07 Å. Two of these also had very weak peaks at 4.32 Å indicative of the presence of traces of tridymite. The fourth isolate had a strong 4.11 Å cristobalite peak and a very weak 4.32 Å peak. The morphology, determined by the scanning electron microscope, varied with the formation temperature indicated by the oxygen isotopic ratio (δ18O), from spheroidal and spongy for the opal-cristobalite formed at ∼25°C (δ18O = 26.0‰) in contrast to angular irregular plates and prisms for that formed at ∼115°C (11.9‰), ∼135°C (7.9 ‰) and ∼170°C (6.8 ‰). The differences in δ18O values are attributed to variation in hydrothermal temperature, but some variability in oxygen isotopic composition of the water is possible. The field-measured temperatures related roughly with the calculated fractionation temperatures except in one site, while the contrast in cristobalite morphology related well to calculated low and high fractionation temperatures. Low-cristobalite of hydrothermal origin in New Zealand (δ18O = 9‰) had characteristic rounded grains with some evidence of platiness. Co-existing quartz grains (δ18O = 10‰) showed more subhedral and irregular prismatic morphology.

This study investigated sex differences in Fe status, and associations between Fe status and endurance and musculoskeletal outcomes, in military training. In total, 2277 British Army trainees (581 women) participated. Fe markers and endurance performance (2·4 km run) were measured at the start (week 1) and end (week 13) of training. Whole-body areal body mineral density (aBMD) and markers of bone metabolism were measured at week 1. Injuries during training were recorded. Training decreased Hb in men and women (mean change (–0·1 (95 % CI –0·2, –0·0) and –0·7 (95 % CI –0·9, –0·6) g/dl, both P < 0·001) but more so in women (P < 0·001). Ferritin decreased in men and women (–27 (95 % CI –28, –23) and –5 (95 % CI –8, –1) µg/l, both P ≤ 0·001) but more so in men (P < 0·001). Soluble transferrin receptor increased in men and women (2·9 (95 % CI 2·3, 3·6) and 3·8 (95 % CI 2·7, 4·9) nmol/l, both P < 0·001), with no difference between sexes (P = 0·872). Erythrocyte distribution width increased in men (0·3 (95 % CI 0·2, 0·4)%, P < 0·001) but not in women (0·1 (95 % CI –0·1, 0·2)%, P = 0·956). Mean corpuscular volume decreased in men (–1·5 (95 % CI –1·8, –1·1) fL, P < 0·001) but not in women (0·4 (95 % CI –0·4, 1·3) fL, P = 0·087). Lower ferritin was associated with slower 2·4 km run time (P = 0·018), sustaining a lower limb overuse injury (P = 0·048), lower aBMD (P = 0·021) and higher beta C-telopeptide cross-links of type 1 collagen and procollagen type 1 N-terminal propeptide (both P < 0·001) controlling for sex. Improving Fe stores before training may protect Hb in women and improve endurance and protect against injury.

Frontal ablation, the combination of submarine melting and iceberg calving, changes the geometry of a glacier's terminus, influencing glacier dynamics, the fate of upwelling plumes and the distribution of submarine meltwater input into the ocean. Directly observing frontal ablation and terminus morphology below the waterline is difficult, however, limiting our understanding of these coupled ice–ocean processes. To investigate the evolution of a tidewater glacier's submarine terminus, we combine 3-D multibeam point clouds of the subsurface ice face at LeConte Glacier, Alaska, with concurrent observations of environmental conditions during three field campaigns between 2016 and 2018. We observe terminus morphology that was predominately overcut (52% in August 2016, 63% in May 2017 and 74% in September 2018), accompanied by high multibeam sonar-derived melt rates (4.84 m d−1 in 2016, 1.13 m d−1 in 2017 and 1.85 m d−1 in 2018). We find that periods of high subglacial discharge lead to localized undercut discharge outlets, but adjacent to these outlets the terminus maintains significantly overcut geometry, with an ice ramp that protrudes 75 m into the fjord in 2017 and 125 m in 2018. Our data challenge the assumption that tidewater glacier termini are largely undercut during periods of high submarine melting.