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Accurate diagnosis of bipolar disorder (BPD) is difficult in clinical practice, with an average delay between symptom onset and diagnosis of about 7 years. A depressive episode often precedes the first manic episode, making it difficult to distinguish BPD from unipolar major depressive disorder (MDD).
Aims
We use genome-wide association analyses (GWAS) to identify differential genetic factors and to develop predictors based on polygenic risk scores (PRS) that may aid early differential diagnosis.
Method
Based on individual genotypes from case–control cohorts of BPD and MDD shared through the Psychiatric Genomics Consortium, we compile case–case–control cohorts, applying a careful quality control procedure. In a resulting cohort of 51 149 individuals (15 532 BPD patients, 12 920 MDD patients and 22 697 controls), we perform a variety of GWAS and PRS analyses.
Results
Although our GWAS is not well powered to identify genome-wide significant loci, we find significant chip heritability and demonstrate the ability of the resulting PRS to distinguish BPD from MDD, including BPD cases with depressive onset (BPD-D). We replicate our PRS findings in an independent Danish cohort (iPSYCH 2015, N = 25 966). We observe strong genetic correlation between our case–case GWAS and that of case–control BPD.
Conclusions
We find that MDD and BPD, including BPD-D are genetically distinct. Our findings support that controls, MDD and BPD patients primarily lie on a continuum of genetic risk. Future studies with larger and richer samples will likely yield a better understanding of these findings and enable the development of better genetic predictors distinguishing BPD and, importantly, BPD-D from MDD.
Samejima identified the possibility of multiple solutions to the likelihood equation (multiple maxima in the likelihood function) for estimating an examinee's trait value for the three-parameter logistic model. In the practical applications that Lord studied, he found that multiple solutions did not occur when the number of items was ≥20. In the present paper, fourteen multiple-choice achievement tests with from 20 to 50 items were examined to see if it was possible for them to produce item response vectors with multiple maxima; such vectors were found for all the tests. Examination of response vectors for large groups of real examinees found that from 0 to 3.1% of them had response vectors with multiple maxima. The implications of these results for multiple-choice tests are discussed.
To evaluate the effectiveness of a radio campaign involving serial 10-minute drama episodes, 10-minute on air discussion of each episode by trained community health workers and 30-minute phone-ins from listeners in improving mothers’ nutrition- and health-related attitudes (HNRAs) and children’s minimum acceptable diet (MAD).
Design:
A two-arm quasi-experimental trial with a pre-post design was used to quantify the effect of a radio campaign on nutrition before and immediately after the 6-month intervention. Difference-in-difference (DID) analysis was performed to assess the intervention’s effect.
Setting:
Saboba district (intervention) and Central Gonja (comparison district) of northern region of Ghana.
Participants:
At baseline, a total of 598 mothers with children aged 6–22 months were randomly selected from the intervention (n 298) and control (n 300) districts. At endline (6 months post-intervention), 252 mother–child dyads in the intervention district and 275 mother–child dyads in the control district were followed up.
Results:
The radio campaign was significantly and positively associated with a change in health- and nutrition-related attitudes (HNRA) over time, with DID in mean attitudes significantly improving more over time in the intervention district than the control (DID = 1·398, P < 0·001). Also, the prevalence of MAD over time in the intervention district was significantly higher than the control district (DID = 16·1 percentage points, P = 0·02) in the presence of food insecurity.
Conclusions:
The study indicates that a radio campaign on nutrition is associated with improved mothers’ HNRA and children’s MAD. Communication interventions on child nutrition targeting low-resource settings should consider this innovative approach.
We present the Sydney Radio Star Catalogue, a new catalogue of stars detected at megahertz to gigahertz radio frequencies. It consists of 839 unique stars with 3 405 radio detections, more than doubling the previously known number of radio stars. We have included stars from large area searches for radio stars found using circular polarisation searches, cross-matching, variability searches, and proper motion searches as well as presenting hundreds of newly detected stars from our search of Australian SKA Pathfinder observations. The focus of this first version of the catalogue is on objects detected in surveys using SKA precursor and pathfinder instruments; however, we will expand this scope in future versions. The 839 objects in the Sydney Radio Star Catalogue are distributed across the whole sky and range from ultracool dwarfs to Wolf-Rayet stars. We demonstrate that the radio luminosities of cool dwarfs are lower than the radio luminosities of more evolved sub-giant and giant stars. We use X-ray detections of 530 radio stars by the eROSITA soft X-ray instrument onboard the Spectrum Roentgen Gamma spacecraft to show that almost all of the radio stars in the catalogue are over-luminous in the radio, indicating that the majority of stars at these radio frequencies are coherent radio emitters. The Sydney Radio Star Catalogue can be found in Vizier or at https://radiostars.org.
This study examined the efficacy of a probiotic in reducing depressive symptom severity in people with subthreshold depression. In a double-blind, randomised, placebo-controlled trial, a probiotic (1 × 10^9 live cells per strain: Limosilactobacillus fermentum LF16 (DSM26956), Lacticaseibacillus rhamnosus LR06 (DSM21981), Lactiplantibacillus plantarum LP01 (LMG P-21021) and Bifidobacterium longum 04 (DSM23233)) or placebo was taken daily for 12 weeks. Data were collected at baseline, 6 and 12 weeks including psychological symptom severity (Beck Depression Inventory, BDI; Patient Health Questionnaire, PHQ; Hospital Anxiety Depression Scale, HADS; and Depression Anxiety and Stress Scale, DASS). Biomarkers of glycaemia, inflammation (high-sensitivity C-reactive protein, hs-CRP), antioxidant status (total glutathione (GSH)) and stress (cortisol awakening response, CAR) were also measured. Thirty-nine participants (nineteen probiotic; twenty placebo) were enrolled. There were no significant between-group differences in the examined psychological symptom severity scores, despite certain significant within-group changes observed in both groups from baseline to 6 and/or 12 weeks of follow-up. Regarding biomarkers, the probiotic group showed reduced hs-CRP (–1520; 95 % CI –273·7, −2766·2 ng/dl) and CAR (–0·28; 95 % CI −0·05, −0·51 μg/dl) at 12 weeks, but increased total GSH (3·9; 95 % CI 0·1, 7·5 ng/dl) at 6 weeks, compared with the placebo. The current study reported favourable decreases in depressive symptoms in both groups. Although the within-group changes observed in the probiotic group were supported by favourable inflammatory, antioxidant status and stress biomarker changes compared with the placebo, further research is required to shed more light on the role of gut microbiota modulation on emotional regulation.
Exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), an environmental endocrine disruptor and model AhR agonist, is linked to skeletal abnormalities, cardiac edema, stunted growth rate, altered metabolism, and neurobehavioral deficits. We have previously reported transgenerational reproductive outcomes of developmental TCDD exposure in adult zebrafish (Danio rerio), an NIH-validated model for developmental and generational toxicology. Using the same paradigm of sublethal TCDD exposure (50 pg/ml) at both 3 and 7 weeks post fertilization (wpf), we investigated several novel endpoints, including longitudinal morphometrics and anxiety-linked behavior, in fish exposed as juveniles. We also assessed developmental abnormalities and neurobehavior in their F1 larval offspring. TCDD exposure induced timepoint-dependent decreases in several craniofacial and trunk morphometrics across juvenile development. In early adulthood, however, only exposed males underwent a transient period of compensatory growth, ending between 7 and 12 months post fertilization (mpf). At 12 mpf, exposed adult fish of both sexes displayed increased exploratory behaviors in a novel tank test. The F1 offspring of parents exposed at both 3 and 7 wpf were hyperactive, but neurobehavioral outcomes diverged depending on parental exposure window. F1 exposure-lineage larvae had increased rates of edema and skeletal abnormalities, but fewer unhatched larvae compared to controls. Parent- and timepoint-specific effects of exposure on abnormality rate were also evaluated; these outcomes were considerably less severe. Our novel behavioral findings expand current knowledge of the long-term and intergenerational consequences of early-life TCDD exposure in a zebrafish model, in addition to delineating minor longitudinal morphometric changes in exposed fish and abnormalities in larval offspring.
Dementia in-patient units (DIU) are mental health wards that care for people living with dementia (PLWD) whose symptoms are causing severe distress or potential risk. DIUs look after some of the most vulnerable and unwell people in society, yet they are environments that are underresearched: a recent systematic review revealed only 36 articles worldwide relating to DIUs. To better understand research priorities in DIUs, we undertook a two-round online Delphi survey of PLWD with experience of DIUs, their carers and professionals who work in DIUs.
Results
Ten research priorities were described and ranked. The top three were how to use non-pharmacological techniques to manage non-cognitive symptoms of dementia, supporting families and better understanding of how to discharge PLWD safely and healthily.
Clinical implications
This is the first Delphi consensus to describe DIU research priorities. This paper will help researchers focus on the areas that matter most to people who use DIUs.
A unique vanadium-titanium-bearing mixed-layered clay is currently being mined as an ore of vanadium at Potash Sulphur Springs, AR. The clay contains 80% expandable portion and has both a 14.22 and 18.24 Å hydration state in addition to the 9.49 Å dehydrated state; ethylene glycol expands this material to 16.69 Å. The 060 reflection for all hydration states is between 1.50 and 1.51 Å indicating the material is dioctahedral. The “mean chemical formula” calculates as(Ca0.08 K0.02 Na0.03)0.13 (Al0.11 V0.90 Ti0.19 Fe0.64 Mg0.14)1.98 (Si3.79 Al0.21)4 O10 (OH)2·nH2O.
Telehealth overcomes common geographical barriers to community/clinic-based healthcare and lifestyle interventions, (1,2) but whether it is a feasible and safe mode of healthcare service delivery for lifestyle-based interventions in those with non-alcoholic fatty liver disease (NAFLD) remains unknown. This study evaluated the feasibility and safety of a home exercise program with dietary advice to increase plant-based protein delivered and monitored by healthcare professionals via telehealth in adults with NAFLD. Secondary aims were to assess changes in macronutrient intake including protein from plant and animal sources, body weight, physical activity and physical function. This was a 12-week pilot feasibility randomised controlled trial conducted in 28 inactive adults (>45 years) with NAFLD. Participants were randomly allocated to receive: 1) a home-based, muscle strengthening exercise program (3 days/week) delivered and monitored remotely by an exercise physiologist using the TeleHab exercise platform/app (VALD Health) plus support from a nutritionist to increase daily protein intake to ~1.2-1.5 g/kg/day from predominately plant-based sources and behavioural change support delivered via 3-4 weekly text messages (Pro-Ex, n = 14) or 2) usual care (UC, n = 14). Feasibility was assessed via retention (defined as ≤10% attrition), adherence [≥66% to the muscle strengthening program and ≥80% to the recommended daily protein serves [total (≥3-3½), plant (≥2) and animal (≤1-1½) per day (via protein checklist)] and safety (intervention-related adverse events). Secondary outcomes included macronutrient intake (3x24-hour records), weight (self-reported), habitual physical activity (PA) [moderate-to-vigorous (MVPA), minutes/week via the Short International Physical Activity Questionnaire], and physical function [30-second sit-to-stand (STS) performance]. Since this was a pilot feasibility study, mean group differences (6 and 12-weeks) were estimated, with 95% confidence intervals, and standardised effects [Cohen D, effect size (ES)] reported for secondary outcomes. Overall, 25 participants (89%) completed the intervention. In Pro-Ex, mean adherence to the exercise program was 52%, while adherence to the recommended plant, animal and total protein serves/day was 32%, 42% and 14% of participants, respectively. One minor exercise-related adverse event occurred from 241 completed sessions over 12 weeks. Relative to UC, Pro-Ex experienced a mean 2.7 (95%CI: 0.9, 4.4; large ES d = 1.29) increase in 30-sec STS number, 46 minute (95%CI: −153, 245; small ES d = 0.19) increase in MVPA, 1.7kg (95%CI: −3.5, 0.2; moderate ES d = 0.54) decrease in body weight, 35.2g (95%CI: 11.0, 59.3; large ES d = 1.23) increase in protein and 8.3g (95%CI:-20.5, 4.0; moderate ES d=-0.57) reduction in saturated fat. In middle-aged and older adults with NAFLD, a home exercise and plant-based dietary protein intervention delivered via telehealth was safe, but not feasible in terms of achieving the desired level of adherence. Despite this, exploratory analysis indicates this mode of healthcare service delivery could play a role to support weight management and improve physical activity and physical function in adults with NAFLD.
OBJECTIVES/GOALS: Launch a case-based learning collaborative on best practices that meet social, emotional and physical health needs of underserved communities as they relate to environmental toxins—specifically those related to the train derailment in OH. Topics discussed could also include disasters and spills, air quality, extreme heat, and water. METHODS/STUDY POPULATION: In response to a call for action delivered by PA’s Acting Secretary of Health, we established a partnership between Penn State CTSI, Project ECHO at Penn State, and Primary Health Network (PHN). PHN is the largest Federally Qualified Health Center in PA, making it uniquely qualified to reach rural providers diagnosing and treating patients impacted by environmental events. Utilizing the ECHO model, we are hosting monthly, 1-hour sessions on environmental determinants of health starting October 2023. Experts in pulmonology, toxicology, atmospheric science, and rural medicine (whom many participants would have limited access to outside of the ECHO platform) and participants have the opportunity to share and learn from their varied experiences exemplifying a culture of ‘all teach, all learn’. RESULTS/ANTICIPATED RESULTS: Project ECHO is an ideal model for upscaling workforce quickly, allowing participants to be responsive in the care of their community, regardless of location and access to specialty clinics. 74 participants across 26 PA counties registered for the series, ranging from PCPs, medical directors, and state officials. Upon registration, nearly half of our direct patient-care participants do not routinely conduct an environmental exposure history and almost 70% report receiving questions from their patients related to how the environment might impact their health. More than half of those providers reported feeling unprepared to answer patients’ questions related to the environment’s impact on their health. Evaluation data will be collected at enrollment, after each session, and post-series. DISCUSSION/SIGNIFICANCE: This series could result in: * Reduction of health disparities caused by environmental events (no cost, virtual learning) * Increased preparedness to quickly address health questions/symptoms related to environmental exposures * Increased awareness of the environmental impacts on health. * Improved testing/treatment for patients
OBJECTIVES/GOALS: to investigate the potential impact of grandparental factors and multigenerational epigenetic inheritance on the development of ASD METHODS/STUDY POPULATION: Our study recruited participants from the CHARGE (Child Autism Risks from Genetics and the Environment) study, including grandparents, parents, and children. A questionnaire was used to gather information about the participants’ exposure to environmental factors. Saliva samples werecollected from 349 participants. Newborn dried blood spotsfrom probands and parents are still being collected from the California New born Registry. DNA was extracted from 349 saliva samples from 85 families and subjected to whole genome bisulfite sequencing (WGBS) to analyze DNA methylation. Sequence alignments and bioinformatic analyses will be performed using R packages called DMRichR and Comethyl. RESULTS/ANTICIPATED RESULTS: Sequence alignments and bioinformatic analyses are ongoing, utilizing DMRichR to identify individual genomic loci associated with ASD in each of the three generations and Comethyl to compare correlation patterns between methylation marks and selected variables, including grand parental exposures. New born blood spot collections of parents and probands are ongoing and will be used to identify potential ASD epigenomic signatures that are tissue and life-stage independent. DISCUSSION/SIGNIFICANCE: This research will provide new insights into the increased prevalence and underlying etiology of ASD that should pave the way for future research in the field. DNA Methylation signatures can help create molecular biomarkers which can be used together with behavioral clinical tests for diagnosis of ASD.
OBJECTIVES/GOALS: Antibiotic treatment sets the stage for intestinal domination by Candida albicanswhich is necessary for development of invasive disease, but the resources driving this bloom remain poorly defined. We sought to determine these factors in order to design novel prophylaxis strategies for reducing gastrointestinal (GI) colonization. METHODS/STUDY POPULATION: We initially developed a generalizable framework, termed metabolic footprinting to determine the metabolites C. albicanspreferentially uses in the mouse GI tract. After identifying the metabolites C. albicansutilizes, we usedin vitro growth assays in the presence and absence of oxygen to validate out metabolomics findings. We next determined if a probiotic E. coli that utilizes oxygen would reduce C. albicanscolonization compared to a mutant E. coli that could not respire oxygen. Finding that oxygen was a necessary resource, we utilized germ-free mice to determine if Clostridiaspp. known to reduce GI oxygen would prevent C. albicanscolonization. Lastly, we sought to see if 5-aminosalicylic acid (5-ASA) could prevent C. albicanscolonization. RESULTS/ANTICIPATED RESULTS: We found that C. albicans preferentially utilizes simple carbohydrates including fructo-oligosaccharides (e.g., 1-kestose), disaccharides (e.g., β-gentiobiose), and alcoholic sugars (e.g., sorbitol) and is able to grow in vitro on minimal media supplemented with either of these nutrients. However, in the hypoxic environment that is found in the “healthy” colon, C. albicans cannot utilize these nutrients. We next found that pre-colonization in a mouse model with a probiotic E. coli significantly reduced C. albicanscolonization, but the mutant E. coli had no effect on colonization. We next showed that Clostridia supplementation restored GI hypoxia and reduced C. albicanscolonization. Remarkably, we found that 5-ASA significantly reduced GI colonization of C. albicans. DISCUSSION/SIGNIFICANCE: We have shown that C. albicans requires oxygen to colonize the GI tract. Importantly, we found that 5-ASA can prevent an antibiotic mediated bloom of C. albicans by restoring GI hypoxia, which warrants additional studies to determine if 5-ASA can be used as an adjunctive prophylactic treatment in high risk patients.
High-resolution transmission electron microscopy (HRTEM) and electron diffraction experiments have been performed on R1 and R> 1 illite/smectite (I/S) samples that from X-ray powder diffraction (XRD) experiments appear to contain well-ordered layer sequences. The HRTEM images confirmed earlier computer image simulations, which suggested that periodicities due to I/S ordering can be imaged in TEM instruments of moderate resolution. The experiments also confirmed that in instruments of this sort, the strongest contrast arising from the compositional difference between I and S layers occurs under rather unusual imaging conditions of strong overfocus. Some selected-area electron diffraction (SAD) patterns showed additional diffraction spots consistent with R1 and R3 ordering. SAD patterns and cross-fringes arising in HRTEM images from non-00l reciprocal lattice rows indicated that the stacking vectors of most adjacent 2:1 layers were not randomly oriented with respect to each other. Thus, the I/S was not fully turbostratic, but instead consisted of very thin, coherently stacked crystallites that extended across the fundamental particles postulated by Nadeau and coworkers.
S/(I + S) ratios were determined for about seventy HRTEM images obtained and interpreted by three different TEM operators. These ratios were consistent with those obtained from standard XRD procedures, suggesting that results obtained by XRD can be used to infer the initial structural state of mixed-layer I/S prior to treatment of samples for XRD experiments. The HRTEM experiments thus demonstrated that the two specimens examined consisted of ordered I/S existing as small crystals, most of which contained more layers than the fundamental particles of Nadeau and coworkers. The non-turbostratic stacking suggests an energetic interaction between the individual fundamental particles, leading to at least two alternative thermodynamic descriptions of these materials. Although the I/S crystals in the present experiments probably were disaggregated into fundamental particles during sample preparation for XRD, the I/S crystals appear to have separated only along the smectite interlayers. If the term “fundamental particle” is to be used for primary, untreated I/S, its original definition should be modified to include not only free particles, but also those that occur as layers within small crystals. It further should be recognized that these particles can interact thermodynamically and crystallographically with their neighbors.
High-resolution transmission electron microscope images of dioctahedral mixed-layer clay structures (illite/smectite) having various substitutional and polytypic schemes were modeled using computer simulation methods. Both one- and two-dimensional calculations were performed using parameters characteristic of a typical range of imaging conditions. One-dimensional images formed by imaging only 00/ diffractions show three important results: (1) The 20-Å periodicity resulting from rigorously ordered R1 illite/smectite can be imaged, but unconventional focus conditions may be necessary. (2) For crystals oriented with the electron beam perfectly parallel to the layers, the brightest fringes in the image correspond to either the octahedral sheets or the interlayer sites, depending on focus conditions. Misorientation of the crystal, however, by only 1° or 2° shifts the positions of the fringes by 1 to 3 Å. Furthermore, in tilted specimens, some defocus values produce images suggesting that smectite layers have a 11–13-Å periodicity, despite the uniform 10-Å periodicity present in the model structure. Thus, direct correlations between image and structure generally should not be made. (3) Two-layer polytypes of pure illite or pure smectite can also produce images with a 20-Å periodicity.
Two-dimensional images additionally showed that the cross fringes produced by some hkl diffractions can be imaged. The simulations showed that these cross fringes ideally might permit the determination of both layer stacking and compositional periodicity, but the fringes are lost by misorientations of a few degrees. These image simulations demonstrated, therefore, that mixed layering of illite and smectite theoretically can be directly imaged by transmission electron microscopy of chemically untreated specimens, but ambiguities may exist in the detailed intepretation of the images.
To make informed decisions, assessment theorists, researchers, and practitioners can evaluate the overlap among (1) relevant theories, (2) empirical contributions, and (3) best practices. Unfortunately, such a task may seem daunting due to the so-called science-practice gap, which can thwart collaboration among these parties. This paper presents an epistemology for delineating the importance of integrating these three sources of knowledge. We then apply this epistemology to show that our current knowledge of assessment and development topics are well integrated in some places, but still quite lacking in others.
End members and species defined with permissible ranges of composition are presented for the true micas, the brittle micas and the interlayer-cation-deficient micas. The determination of the crystallochemical formula for different available chemical data is outlined, and a system of modifiers and suffixes is given to allow the expression of unusual chemical substitutions or polytypic stacking arrangements. Tables of mica synonyms, varieties, ill-defined materials and a list of names formerly or erroneously used for micas are presented. The Mica Subcommittee was appointed by the Commission on New Minerals and Mineral Names (“Commission”) of the International Mineralogical Association (IMA). The definitions and recommendations presented were approved by the Commission.
Livestock abortion is a source of economic loss for farmers, but its economic impact has not been estimated in many Low and Middle-Income Countries. This article presents an estimation methodology and estimates for the gross and net cost of an abortion based on a sample of livestock-owning households in three regions of northern Tanzania and market data. We then generate aggregate estimates of abortion losses across Tanzania. We estimate annual gross and net annual losses of about $263 Million (about TZS 600 billion) and $131 million (about TZS 300 billion), respectively.
Languages vary in the mapping of relational terms onto events. For instance, English motion descriptions favor manner (how something moves) verbs over path (where something move) verbs, whereas those of other languages, like Spanish, show the opposite pattern. While these lexicalization biases are malleable, adopting a novel lexicalization pattern can be slow for second language learners. One potential mechanism for learning non-native verb mappings is cross-situational statistical learning (CSSL). However, the application of CSSL to verbs is limited and does not explicitly examine how lexicalization biases may complicate adults’ ability to resolve the referential uncertainty of multiple referents. We ask English-speaking monolingual adults to learn the mappings of ten verbs via CSSL. Verbs mapped onto either manner or path of motion, with the other event component held constant. Adults in both conditions demonstrated successful learning of novel verbs, with adults learning the manner verbs showing more consistent performance across accepting correct referents and rejecting incorrect ones. Our results are the first to demonstrate adults’ use of CSSL to acquire verb meanings that both align with and cut against native lexicalization biases and suggest a limited influence of lexicalization biases on adults’ learning in idealized CSSL conditions.
The coefficient of friction of clay minerals at the micro-scale has generally not been studied due to difficulties in obtaining measurements in a bulk-soil volume undergoing shear at such small scales. Information on friction at the micro-scale may provide insight into grain-scale processes that operate in bulk samples or in natural faults. The objective of this study was to develop a method to measure the microscale friction coefficient of smectites. The experiments described show that the axial atomic force microscopy method can be adapted to easily obtain accurate coefficient of friction (μ) measurements for smectites from force curves involving colloidal probes. The method allows for the measurements to be performed over spatial scales of a few μm, can be carried out under dry conditions or a wide range of aqueous solutions, and requires no calibration beyond making a few microscopic measurements of the probe. This method provides measurements of micro-scale normal and shear forces between minerals, which can be used for a variety of applications such as the study of shear deformation, consolidation, and fault dynamics. Control tests of silica on mica (μ = 0.29±0.02) agree with literature values where limits indicate one standard deviation. Coefficient of friction values for wet and dry Na-montmorillonite were determined to be 0.20±0.03 and 0.72±0.03, respectively.