Mutant clones in normal epithelium outcompete and eliminate emerging tumours.

Human epithelial tissues accumulate cancer-driver mutations with age1-9, yet tumour formation remains rare. The positive selection of these mutations suggests that they alter the behaviour and fitness of proliferating cells10-12. Thus, normal adult tissues become a patchwork of mutant clones competing for space and survival, with the fittest clones expanding by eliminating their less competitive neighbours11-14. However, little is known about how such dynamic competition in normal epithelia influences early tumorigenesis. Here we show that the majority of newly formed oesophageal tumours are eliminated through competition with mutant clones in the adjacent normal epithelium. We followed the fate of nascent, microscopic, pre-malignant tumours in a mouse model of oesophageal carcinogenesis and found that most were rapidly lost with no indication of tumour cell death, decreased proliferation or an anti-tumour immune response. However, deep sequencing of ten-day-old and one-year-old tumours showed evidence of selection on the surviving neoplasms. Induction of highly competitive clones in transgenic mice increased early tumour removal, whereas pharmacological inhibition of clonal competition reduced tumour loss. These results support a model in which survival of early neoplasms depends on their competitive fitness relative to that of mutant clones in the surrounding normal tissue. Mutant clones in normal epithelium have an unexpected anti-tumorigenic role in purging early tumours through cell competition, thereby preserving tissue integrity.

"God was with me": A qualitative study of Christian meaning-making among refugees.

In this consensual qualitative research study, we investigated the role of refugees' Christian faith in meaning-making coping. High percentages of religiosity in refugee populations support the need to understand the role of religion in their coping processes. Interviews with 20 Christian refugees from 10 African and Asian countries revealed that participants drew heavily from their faith resources to cope with their experiences. Specifically, refugees reported coping practices that included trust in God, prayer, intimacy with God, spiritual surrender, lament, worship, and social support. Although many participants described spiritual struggles, including doubting God, feeling distant from God, and questioning God, most found meaning amid refugee-related suffering and reported perspective shifts, a deepening of faith, seeing suffering as part of God's plan, experiencing a deepened sense of purpose, and growing in the likeness of Christ. Refugees also reported growth through suffering in the form of gratitude, altruism, testimony, and humility. Clinical implications include encouraging the use of religious resources for meaning-making and supporting the resolution of spiritual struggles.

Development of an Automated Ultrasound Signal Indicator of Lung Interstitial Syndrome.

OBJECTIVES: The number and distribution of lung ultrasound (LUS) imaging artifacts termed B-lines correlate with the presence of acute lung disease such as infection, acute respiratory distress syndrome (ARDS), and pulmonary edema. Detection and interpretation of B-lines require dedicated training and is machine and operator-dependent. The goal of this study was to identify radio frequency (RF) signal features associated with B-lines in a cohort of patients with cardiogenic pulmonary edema. A quantitative signal indicator could then be used in a single-element, non-imaging, wearable, automated lung ultrasound sensor (LUSS) for continuous hands-free monitoring of lung fluid. METHODS: In this prospective study a 10-zone LUS exam was performed in 16 participants, including 12 patients admitted with acute cardiogenic pulmonary edema (mean age 60 ± 12 years) and 4 healthy controls (mean age 44 ± 21). Overall,160 individual LUS video clips were recorded. The LUS exams were performed with a phased array probe driven by an open-platform ultrasound system with simultaneous RF signal collection. RF data were analyzed offline for candidate B-line indicators based on signal amplitude, temporal variability, and frequency spectrum; blinded independent review of LUS images for the presence or absence of B-lines served as ground truth. Predictive performance of the signal indicators was determined with receiving operator characteristic (ROC) analysis with k-fold cross-validation. RESULTS: Two RF signal features-temporal variability of signal amplitude at large depths and at the pleural line-were strongly associated with B-line presence. The sensitivity and specificity of a combinatorial indicator were 93.2 and 58.5%, respectively, with cross-validated area under the ROC curve (AUC) of 0.91 (95% CI = 0.80-0.94). CONCLUSION: A combinatorial signal indicator for use with single-element non-imaging LUSS was developed to facilitate continuous monitoring of lung fluid in patients with respiratory illness.

Advanced crystallisation methods for small organic molecules.

Molecular materials based on small organic molecules often require advanced structural analysis, beyond the capability of spectroscopic techniques, to fully characterise them. In such cases, diffraction methods such as single crystal X-ray diffraction (SCXRD), are one of the most powerful tools available to researchers, providing molecular and structural elucidation at atomic level resolution, including absolute stereochemistry. However SCXRD, and related diffraction methods, are heavily dependent on the availability of suitable, high-quality crystals, thus crystallisation often becomes the major bottleneck in preparing samples. Following a summary of classical methods for the crystallisation of small organic molecules, this review will focus on a number of recently developed advanced methods for crystalline material sample preparation for SCXRD. This review will cover two main areas of modern small organic molecule crystallisation, namely the inclusion of molecules within host complexes (e.g., "crystalline sponge" and tetraaryladamantane based inclusion chaperones) and the use of high-throughput crystallisation, employing "under-oil" approaches (e.g., microbatch under-oil and ENaCt). Representative examples have been included for each technique, together with a discussion of their relative advantages and limitations to aid the reader in selecting the most appropriate technique to overcome a specific analytical challenge.

Reduction in N-Acetylglucosaminyltransferase-I Activity Decreases Survivability and Delays Development of Zebrafish.

A lack of complex and hybrid types of N-glycans in mice is embryonically lethal due to neural tube maldevelopment. N-acetylglucosaminyltransferase-I (GnT-I; Mgat1) catalyzes a required step for converting oligomannose N-glycans into hybrid and complex N-glycans. Unlike mice, zebrafish have two Mgat1a/b genes. Herein, CRISPR/Cas9 technology was used to knockdown GnT-Ib activity in zebrafish, referred to as Mgat1b-/-, to examine the impact of a decrease in complex types of N-glycans on survival and development, and sensory and motor functions. Genotyping verified the occurrence of edited Mgat1b, and LC-ESI-MS and lectin blotting identified higher levels of oligomannose and lower levels of complex N-glycans in Mgat1b-/- relative to Wt AB. The microscopic visualization of developmental stages and locomotor studies using an automated tracking unit and manual touch assays revealed reduced survivability, and delayed motor and sensory functions in Mgat1b-/-. Moreover, embryonic staging linked reduced survivability of Mgat1b-/- to disruption in brain anlagen formation. Birefringence measurements supported delayed skeletal muscle development, which corresponded with motor and sensory function impediments in Mgat1b-/-. Furthermore, GnT-Ib knockdown hindered cardiac activity onset. Collectively, Mgat1b-/- displayed incomplete penetrance and variable expressivity, such that some died in early embryonic development, while others survived to adulthood, albeit, with developmental delays. Thus, the results reveal that reducing the amount of complex-type N-glycans is unfavorable for zebrafish survival and development. Moreover, our results support a better understanding of human congenital disorders of glycosylation.

Osteoarthritis year in review 2022: Epidemiology & therapy.

This 'Year in Review' provides a synopsis of key research themes and individual studies from the clinical osteoarthritis (OA) field, focused on epidemiology and therapy. The electronic database search for the review was adapted from the 2021 year in review search, to increase search specificity for relevant study designs, and was conducted in Medline, Embase and medRxiv (31st March 2021 to 4th March 2022). Following screening for eligibility, studies were grouped according to their key research design, including reviews, cohorts and randomised trials. 11 key themes emerged, including the importance of several comorbidities in predicting OA incidence and prevalence, surgical approaches that can reduce the risk of post-traumatic OA, the heterogenous but nevertheless relatively stable nature of OA subgroup trajectories, the paucity of robust studies particularly of surgery for OA and the very modest benefit of many therapies under evaluation in trials. A particular interest of the authors was to consider whether new studies are helping determine how to better ensure the right patient with OA is matched to the right treatment at the right time. There are several new studies developing improved predictive models through big data analytics and machine learning which show promise, need validation, and may support new approaches to stratified care.

First Direct Measurement Constraining the

The rate of the final step in the astrophysical αp process, the ^{34}Ar(α,p)^{37}K reaction, suffers from large uncertainties due to a lack of experimental data, despite having a considerable impact on the observable light curves of x-ray bursts and the composition of the ashes of hydrogen and helium burning on accreting neutron stars. We present the first direct measurement constraining the ^{34}Ar(α,p)^{37}K reaction cross section, using the Jet Experiments in Nuclear Structure and Astrophysics gas jet target. The combined cross section for the ^{34}Ar,Cl(α,p)^{37}K,Ar reaction is found to agree well with Hauser-Feshbach predictions. The ^{34}Ar(α,2p)^{36}Ar cross section, which can be exclusively attributed to the ^{34}Ar beam component, also agrees to within the typical uncertainties quoted for statistical models. This indicates the applicability of the statistical model for predicting astrophysical (α,p) reaction rates in this part of the αp process, in contrast to earlier findings from indirect reaction studies indicating orders-of-magnitude discrepancies. This removes a significant uncertainty in models of hydrogen and helium burning on accreting neutron stars.

The time is now: making the case for a UK registry of deployment of radiology artificial intelligence applications.

Artificial intelligence (AI)-based healthcare applications (apps) are rapidly evolving, and radiology is a target specialty for their implementation. In this paper, we put the case for a national deployment registry to track the spread of AI apps into clinical use in radiology in the UK. By gathering data on the specific locations, purposes, and people associated with AI app deployment, such a registry would provide greater transparency on their spread in the radiology field. In combination with other regulatory and audit mechanisms, it would provide radiologists and patients with greater confidence and trust in AI apps. At the same time, coordination of this information would reduce costs for the National Health Service (NHS) by preventing duplication of piloting activities. This commentary discusses the need for a UK-wide registry for such apps, its benefits and risks, and critical success factors for its establishment. We conclude by noting that a critical window of opportunity has opened up for the development of a deployment registry, before the current pattern of localised clusters of activity turns into the widespread proliferation of AI apps across clinical practice.

Invited review: Corrected milk: Reconsideration of common equations and milk energy estimates.

Corrected milk equations were developed in attempts to bring milk weights to a standardized basis for comparison by expressing the weight and composition of milk as corrected to the energy content of milk of a specific composition. Expressed as milk weights familiar on farm and in commerce, this approach integrates energy contributions of the dissimilar components to make the mass units more comparable. Such values are applied in evaluating feed efficiency, lactation performance, and global milk production, as functional units for lifecycle assessments, and in translation of research results. Corrected milk equations are derived from equations relating milk gross energy to milk composition. First, a milk energy equation is used to calculate the energy value of the milk composition to correct to (e.g., 0.695 Mcal/kg for milk with 3.5% fat, 3.05% true protein, and 4.85% lactose). That energy value is divided into the energy equation to give the corrected milk equation. Confusion has arisen, as different equations purport to correct to the same milk composition; their differences are based on uses of different energy equations or divisors. Accuracy of corrected milk equations depends on the accuracy of the energy equations used to create them. Energy equations have evolved over time as different milk component analyses have become more available. Inclusion of multiple milk components more accurately predicts milk energy content than does fat content alone. Omission of components from an equation requires the assumption that their content in milk is constant or highly correlated with an included component. Neither of these assumptions is true. Milk energy equations evaluated on a small data set of measured milk values have demonstrated that equations that incorporate protein, fat, and lactose contents multiplied by the gross energy of each component more closely predict milk energy than equations containing fewer components or regression-derived equations. This provides a tentative recommendation for using energy equations that include the 3 main milk components and their gross energy multipliers for predicting milk energy and deriving corrected milk equations. Accuracy of energy equations is affected by the accuracy of gross energy values of individual components and variability of milk composition. Lactose has consistent reported gross energy values. In contrast, gross energy of milk fat and protein vary as their compositional profiles change. Future refinements could assess accuracy of milk fat and protein gross energy and whether that appreciably improves milk energy predictions. Fat gross energy has potential to be calculated using the milk fatty acid profile, although the influence on gross energy may be small. For research, direct reporting of milk energy values, rather than corrected milk, provides the most explicit, least manipulated form of the data. However, provision of corrected milk values in addition to information on components can serve to translate the energy information to a form familiar to and widely used in the field. When reporting corrected milk data, the corrected milk equation, citation for the energy equation used, and composition and energy contents of the corrected milk must be described to make clear what the values represent.

Methane emission, nutrient digestibility, and rumen microbiota in Holstein heifers fed 14 different grass or clover silages as the sole feed.

This experiment investigated the variation in enteric methane production and associated gas exchange parameters, nutrient digestibility, rumen fermentation, and rumen microbiome when a range of silages based on different forage types (grass or clover), and different species within the 2 types, were fed as the sole feed to heifers. Three grass species (perennial ryegrass, festulolium, and tall fescue) and 2 clover species (red clover and white clover) were included. Perennial ryegrass was harvested at 2 maturity stages in the primary growth, white clover was harvested once in the primary growth, and 4 cuts of festulolium and tall fescue and 3 cuts of red clover were harvested during the growing season, giving 14 different silage batches in total. Sixteen Holstein heifers 16 to 21 mo old and 2 to 5 mo in pregnancy were fed the silages ad libitum as the sole feed in an incomplete crossover design. Each silage was fed to 4 heifers, except for the 2 perennial ryegrass silages, which were fed to 8 heifers; in total 64 observations. The CH4 production was measured for 3 d in respiration chambers. Heifers fed clover silages had higher dry matter intake (DMI) compared with heifers fed grass silages, and heifers fed tall fescue silages had the numerically the lowest DMI. Compared with grass silages, feeding clover silages led to higher crude protein digestibility but lower neutral detergent fiber (NDF) digestibility. Rumen pH was higher in heifers fed clover silages compared with those fed grass silages. Based on composition analysis, the rumen microbiota of the heifers clustered clearly according to forage type and species. More specifically, 7 of the 34 dominating rumen bacterial genus-level groups showed higher relative abundances for the clover silages, whereas 7 genus-level groups showed higher abundances for the grass silages. Methane yield was higher for heifers fed grass silages than for those fed clover silages when methane production was related to dry matter and digestible organic matter intake, whereas the opposite was seen when related to NDF digestion. The gross energy lost as methane (CH4 conversion factor, %) reduced from 7.5% to 6.7%, equivalent to an 11% reduction. The present study gives the outlines for choosing the optimal forage type and forage species with respect to nutrient digestibility and enteric methane emission in ruminants.

A content review of state tobacco pre-emption laws in the US.

OBJECTIVES: State ceiling pre-emption laws effectively limit the authority of local governments to regulate numerous public health issues, including tobacco. While general trends in the number of state tobacco pre-emption laws have been well-documented, less is known about the specific content of these laws. This study provides a comprehensive analysis of the content of current state tobacco pre-emption laws and captures the salient features of these laws. STUDY DESIGN: This was a comparative analysis of tobacco pre-emption laws in the United States. METHODS: The study team collected data about tobacco pre-emption laws from the Centers for Disease Control and Prevention's State Tobacco Activities Tracking and Evaluation System. Trained legal researchers further verified and reviewed each law's content using the Westlaw database. A coding scheme was developed to capture and analyse these laws' most salient features. RESULTS: State tobacco pre-emption laws use various terms to indicate the pre-emption of a local authority, including supersede, pre-empt, uniform, exclusive, and consistent. State laws cover numerous general topics and vary widely in explicit terminology of authorities and fields pre-empted. Several state laws included grandfathering exceptions and a few allowed exceptions for particular local jurisdictions. CONCLUSIONS: State laws that undermine local tobacco control efforts from implementing more stringent laws pose a threat to public health. These laws vary widely in their scope across the U.S., and local jurisdictions should be empowered to enact and maintain tobacco control measures that protect their communities from the harms of tobacco use and exposure.

When suffering contradicts belief: measuring theodical struggling.

Global meaning systems help people make sense of their experiences, but suffering can violate global meaning and create distress. One type of potential violation is conflict between one's experience of suffering and one's deeply-held beliefs about God as loving, powerful, and just. The problem of theodicy-why an all-powerful and all-loving God would allow suffering-has long been an important theological and philosophical concern, but little is known about how theodicy plays out psychologically for religious individuals facing serious life difficulties. To address this issue within a specific religious tradition, Christianity, we drew upon philosophy, Christian theology, and psychology to develop the construct of theodical struggling. Through theological and philosophical input, we generated a 28-item pool and conducted 10 cognitive interviews with a diverse sample of Christian adults. In three consecutive online studies of Christian adult samples, we reduced the scale to 11 items through PCA, found a strong one-factor solution using EFA, and found support for the one-factor solution along with preliminary reliability and validity. This newly-developed Theodical Struggling Scale represents an important advance in understanding individuals' experiences of ruptures in their beliefs regarding God's goodness and paves the way for future research on this topic. Supplementary Information: The online version contains supplementary material available at 10.1007/s12144-023-04642-w.

First Series Using Ultrasonic Propulsion and Burst Wave Lithotripsy to Treat Ureteral Stones.

PURPOSE: Our goal was to test transcutaneous focused ultrasound in the form of ultrasonic propulsion and burst wave lithotripsy to reposition ureteral stones and facilitate passage in awake subjects. MATERIALS AND METHODS: Adult subjects with a diagnosed proximal or distal ureteral stone were prospectively recruited. Ultrasonic propulsion alone or with burst wave lithotripsy was administered by a handheld transducer to awake, unanesthetized subjects. Efficacy outcomes included stone motion, stone passage, and pain relief. Safety outcome was the reporting of associated anticipated or adverse events. RESULTS: Twenty-nine subjects received either ultrasonic propulsion alone (n = 16) or with burst wave lithotripsy bursts (n = 13), and stone motion was observed in 19 (66%). The stone passed in 18 (86%) of the 21 distal ureteral stone cases with at least 2 weeks follow-up in an average of 3.9±4.9 days post-procedure. Fragmentation was observed in 7 of the burst wave lithotripsy cases. All subjects tolerated the procedure with average pain scores (0-10) dropping from 2.1±2.3 to 1.6±2.0 (P = .03). Anticipated events were limited to hematuria on initial urination post-procedure and mild pain. In total, 7 subjects had associated discomfort with only 2.2% (18 of 820) propulsion bursts. CONCLUSIONS: This study supports the efficacy and safety of using ultrasonic propulsion and burst wave lithotripsy in awake subjects to reposition and break ureteral stones to relieve pain and facilitate passage.

Walking-related knee contact forces and associations with knee pain across people with mild, moderate and severe radiographic knee osteoarthritis: a cross-sectional study.

OBJECTIVE: To investigate knee contact forces (KCFs), and their relationships with knee pain, across grades of radiographic knee osteoarthritis (OA) severity. DESIGN: Cross-sectional exploratory analysis of 164 participants with medial knee OA. Radiographic severity was classified as mild (grade 2), moderate (grade 3) or severe (grade 4) using the Kellgren & Lawrence (KL) scale. Walking knee pain was assessed using an 11-point numerical rating scale. External knee adduction moment (external KAM) and internal muscle forces were used to calculate medial, lateral and total KCFs using a musculoskeletal computational model. Force-time series across stance phase of gait were compared across KL grades using Statistical Parametric Mapping. Associations between KCFs and pain across KL grades were assessed using linear models. RESULTS: Medial KCFs during early and middle stance were higher in participants with KL3 and KL4 compared to those with KL2. In contrast, lateral KCFs were higher in those with KL2 compared to KL3 and KL4 in middle to late stance. The external loading component (i.e., KAM) of the medial KCF during middle to late stance was also greater in participants with KL3 and KL4 compared to those with KL2, whereas the internal (i.e., muscle) component was greater in those with KL3 and KL4 compared to KL3 during early stance. There were no associations between medial KCF and knee pain in any KL grade. CONCLUSIONS: Medial and lateral KCFs differ between mild, moderate and severe radiographic knee OA but are not associated with knee pain severity for any radiographic OA grade.

How does hip osteoarthritis differ from knee osteoarthritis?

Hip and knee osteoarthritis (OA) are leading causes of global disability. Most research to date has focused on the knee, with results often extrapolated to the hip, and this extends to treatment recommendations in clinical guidelines. Extrapolating results from research on knee OA may limit our understanding of disease characteristics specific to hip OA, thereby constraining development and implementation of effective treatments. This review highlights differences between hip and knee OA with respect to prevalence, prognosis, epigenetics, pathophysiology, anatomical and biomechanical factors, clinical presentation, pain and non-surgical treatment recommendations and management.

Constraining the

The ^{30}P(p,γ)^{31}S reaction plays an important role in understanding the nucleosynthesis of A≥30 nuclides in oxygen-neon novae. The Gaseous Detector with Germanium Tagging was used to measure ^{31}Cl ß-delayed proton decay through the key J^{π}=3/2^{+}, 260-keV resonance. The intensity I_{ßp}^{260}=8.3_{-0.9}^{+1.2}×10^{-6} represents the weakest ß-delayed, charged-particle emission ever measured below 400 keV, resulting in a proton branching ratio of Γ_{p}/Γ=2.5_{-0.3}^{+0.4}×10^{-4}. By combining this measurement with shell-model calculations for Γ_{γ} and past work on other resonances, the total ^{30}P(p,γ)^{31}S rate has been determined with reduced uncertainty. The new rate has been used in hydrodynamic simulations to model the composition of nova ejecta, leading to a concrete prediction of ^{30}Si:^{28}Si excesses in presolar nova grains and the calibration of nuclear thermometers.

Quenching of Single-Particle Strength in A=15 Nuclei.

Absolute cross sections for the addition of s- and d-wave neutrons to ^{14}C and ^{14}N have been determined simultaneously via the (d,p) reaction at 10 MeV/u. The difference between the neutron and proton separation energies, ΔS, is around -20 MeV for the ^{14}C+n system and +8 MeV for ^{14}N+n. The population of the 1s_{1/2} and 0d_{5/2} orbitals for both systems is reduced by a factor of approximately 0.5 compared with the independent single-particle model, or about 0.6 when compared with the shell model. This finding strongly contrasts with results deduced from intermediate-energy knockout reactions between similar nuclei on targets of ^{9}Be and ^{12}C. The simultaneous technique used removes many systematic uncertainties.

Substitution of cane molasses for corn grain at two levels of degradable protein. I. Lactating cow performance, nutrition model predictions, and potential basis for butterfat and intake responses.

Little data is presently available on our ability to predict the combined effect of modifying diets with feeds rich in sugars or starch (ST) and rumen-degradable protein (RDP) on the performance of high-producing dairy cows. The objective of this study was to compare responses of 59 lactating Holstein cows to substitution of cane molasses (Mol) for dry corn grain (CG) at 3 levels of Mol and 2 levels of RDP (+RDP or -RDP) in a randomized complete block design with a 3 × 2 factorial arrangement of treatments. Also, lactation responses predicted by 2 nutritional models were compared with observed responses, with Mol composition entered so that nonnutritive materials in Mol were not counted as potentially digestible carbohydrate. We hypothesized that dry matter (DM) intake and milk fat percentage responses would increase with increasing Mol and would potentially be greater with +RDP. For evaluation of the nutritional models, we adopted the null hypothesis that observed and predicted lactation performance would not differ. Cows were individually fed a common diet during a 2-wk covariate period followed by 8 wk on experimental diets. Diets were formulated to be isonitrogenous and provide similar amounts of ST and water-soluble carbohydrates. Experimental diets contained, on a DM basis, 35% corn silage, 20% alfalfa silage, and 16.6% crude protein. The 0, 5.25, and 10.5% Mol diets respectively contained 19.0, 14.5, and 10.0% CG; 28, 25, and 22% ST; and 5.5, 8.5, and 11.5% water-soluble carbohydrates. At 10 wk on study, cows averaged 45.5 kg of energy-corrected milk (ECM). The DM intake (DMI), and yields of milk, milk protein, and ECM, and milk N/intake N declined linearly with increasing Mol. Differences among diets were not detected for milk fat yield and ECM/DMI. No RDP or interaction effects were detected for these measures. That milk production efficiency did not differ across diets suggests that DMI was a primary driver of performance. The similar ECM/DMI and maintenance of milk fat yield would not have been predicted based on Mol and CG composition but may relate to differences in fermentation rates and products. As explanation for these results, we hypothesize that more rapid ruminal evolution of volatile fatty acids post-ingestion with Mol compared with CG may have provided masses of acetate and butyrate in excess of existing energy and synthetic needs that were shunted to milk fat production, and of propionate that depressed intake. The 2001 Dairy National Research Council model and the Cornell Net Carbohydrate and Protein System 6.55 in Nutritional Dynamic System Professional (2021) estimates of metabolizable protein-allowable ECM underestimated actual ECM for +RDP diets by 4.5 and 2.3 kg, respectively, and came close or overestimated for -RDP diets by 0.25 and 5.0 kg, respectively. Prediction discrepancies suggest issues with valuation of dietary protein based on degradability. Improved understanding of factors mediating these results would likely enhance our ability to predict animal responses.

Substitution of molasses for corn grain at two levels of degradable protein. II. Effects on ruminal fermentation, digestion, and nitrogen metabolism.

Our objective was to evaluate cow N metabolism and ruminal measures with diets containing 3 different levels of molasses or finely ground dry corn grain with 2 levels of ruminally degradable protein (RDP). Twelve lactating, ruminally cannulated Holstein cows (parity 2.25 ± 0.62; 185 ± 56 DIM; 41.3 ± 6.3 kg of milk initially) were individually fed in an experiment designed as a split-plot, replicated 3 × 3 Latin square, where each period lasted 28 d. Six diets were formulated according to a 2 × 3 factorial arrangement of treatments, where 2 levels of RDP (+RDP and -RDP) were fed throughout the experiment as the whole plot, and 3 levels of molasses (0, 5.25, or 10.50% of dry matter replacing finely ground dry corn grain) were fed in sequences of the Latin squares. Dry matter intake did not differ by diet, although ash intake increased linearly with increasing molasses. Ruminal pH, organic acid concentration, and ammonia concentration were not affected by diet. Molar percentages of ruminal acetate decreased and butyrate increased linearly with increasing levels of molasses. Ruminal free amino acid concentration was greater for +RDP, whereas branched-chain volatile fatty acids declined linearly with increasing molasses. Rumen content mass, ruminal liquid, and ruminal acetate pool size was greater for -RDP, although ruminal lactate pool size tended to be greater with +RDP. Increased ruminal lactate when increasing molasses with high RDP should be explored further, to optimize microbial efficiency and rumen health. Total-tract apparent dry matter digestibility based on spot sampling was not affected by diet; however, ash digestibility increased linearly with increasing levels of molasses. Calculated urine output was greater for cows fed diets with increasing levels of molasses and for cows fed +RDP. Grams of N distributed to excretion pools were not different across diets, although, as molasses increased, a lower proportion of N intake was excreted in urine. Overall, the results from this experiment showed that dairy cows used dietary carbohydrates differently during ruminal fermentation, with increasing molasses resulting in increased butyrate molar proportions at the expense of acetate. Additionally, RDP tended to modify the effects of carbohydrate fermentation, resulting in a tendency for increasing lactate molar pool size only in diets with greater RDP, although this did not ultimately affect ruminal pH.

Tangible Experiences of Grace: A Qualitative Investigation of Divine Grace in Roman Catholics.

According to Catholic theology, God offers a gift of love, known as divine grace, to all of humanity. This gift of divine grace is the gift of redemption and forgiveness of sins from God that is offered to everyone who decides to acknowledge and accept it. Grace is central to the lived experience of many Christians. This qualitative study examined how Catholics perceive and experience divine grace using interviews that assessed perceptions of divine grace in 29 practicing adult Catholics. A grounded theory analysis resulted in themes indicating that these Catholics view God's divine grace as a tangible gift that is undeserved though continuously offered. The participants' experience of God's grace is not just an abstract theological concept but an embodied aspect of religious life with which believers can interact in many powerful ways. Three characteristics of God's divine grace (i.e., salvific grace, cooperation through free will, primacy of conscience and the afterlife) and three mechanisms to experiencing God's grace (i.e., sacraments, prayer and meditation, saints) are presented.