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1.
Mol Ecol Resour ; 2023 Sep 13.
Article in English | MEDLINE | ID: mdl-37702134

ABSTRACT

We have developed a flexible undergraduate curriculum that leverages the place-based research of environmental microbiomes to increase the number of Indigenous researchers in microbiology, data science and scientific computing. Monitoring Environmental Microbiomes (MEM) provides a curriculum and research framework designed to integrate an Indigenous approach when conducting authentic scientific research and to build interest and confidence at the undergraduate level. MEM has been successfully implemented as a short summer workshop to introduce computing practices in microbiome analysis. Based on self-assessed student knowledge of topics and skills, increased scientific confidence and interest in genomics careers were observed. We propose MEM be incorporated in a scalable course-based research experience for undergraduate institutions, including tribal colleges and universities, community colleges and other minority serving institutions. This coupled curricular and research framework explicitly considers cultural perspectives, access and equity to train a diverse future workforce that is more informed to engage in microbiome research and to translate microbiome science to benefit community and environmental health.

3.
Res Sports Med ; 29(1): 43-55, 2021.
Article in English | MEDLINE | ID: mdl-32326755

ABSTRACT

Prefabricated foot orthosis (FO) is commonly worn for flat foot management. This study aimed to investigate the kinetic and perceptual effects of wearing prefabricated FO among flat-footed athletes during bouts of sprints. Twenty male sprint-based sports athletes who had flat foot bilaterally ran at three test speeds (5, 6, 7 m/s) under two conditions: prefabricated FO and sham FO. Ground reaction force (GRF) variables and subjective perceptions were recorded. Kinetic variability of GRF variables were computed to indicate step-to-step variance. Biomechanically, wearing prefabricated FOs increased vertical impact force (p =.005), loading rate (p =.001), and kinetic variability of peak propulsive force (p =.038) and loading rate (p =.019) during sprinting speeds across 5 to 7 m/s. Subjectively, prefabricated FO provided better arch support (p =.001) but resulted in reduced forefoot cushioning (p =.001), heel cushioning (p =.002), and overall comfort (p =.008).


Subject(s)
Flatfoot/physiopathology , Foot Orthoses , Running/physiology , Adult , Athletes , Biomechanical Phenomena , Cross-Over Studies , Humans , Male , Perception , Prosthesis Design , Random Allocation , Young Adult
4.
Meat Sci ; 154: 96-108, 2019 Aug.
Article in English | MEDLINE | ID: mdl-31022587

ABSTRACT

The objective was to control intrinsic and extrinsic factors associated with the production and slaughter of pigs to determine effects of sire line (Pietrain vs. Duroc ancestry) on growth performance, carcass and belly characteristics, and commercial bacon yields of growing-finishing pigs. There were no differences in growth performance (P ≥ 0.08) or belly processing characteristics (P ≥ 0.09). Pietrain sired pigs had a greater lean yield (P ≤ 0.01). Duroc sired pigs had darker, more highly marbled loins (P ≤ 0.04) and thicker bellies (P < 0.001). Bacon from Pietrain sired pigs had a greater (P = 0.04) lean to fat ratio with 1.58% increase (P = 0.04) in average bacon slice lean. Barrows had more highly marbled loins (P ≤ 0.01) and thicker bellies (P < 0.001) than gilts. Bacon from barrows had a greater slice area (P < 0.001) while bacon from gilts had a greater lean to fat ratio (P = 0.04).


Subject(s)
Red Meat/standards , Sus scrofa/growth & development , Adipose Tissue , Animals , Body Composition , Breeding , Female , Male , Meat Products/standards , Sus scrofa/genetics
5.
Neurosci Res ; 149: 1-13, 2019 Dec.
Article in English | MEDLINE | ID: mdl-30389571

ABSTRACT

Insulin-like growth factor 2 (IGF2) is abundantly expressed in the central nervous system (CNS). Recent evidence highlights the role of IGF2 in the brain, sustained by data showing its alterations as a common feature across a variety of psychiatric and neurological disorders. Previous studies emphasize the potential role of IGF2 in psychiatric and neurological conditions as well as in memory impairments, targeting IGF2 as a pro-cognitive agent. New research on animal models supports that upcoming investigations should explore IGF2's strong promising role as a memory enhancer. The lack of effective treatments for cognitive disturbances as a result of psychiatric diseases lead to further explore IGF2 as a promising target for the development of new pharmacology for the treatment of memory dysfunctions. In this review, we aim at gathering all recent relevant studies and findings on the role of IGF2 in the development of psychiatric diseases that occur with cognitive problems.


Subject(s)
Insulin-Like Growth Factor II/metabolism , Insulin-Like Growth Factor II/physiology , Mental Disorders/metabolism , Mental Disorders/physiopathology , Nervous System Diseases/metabolism , Nervous System Diseases/physiopathology , Animals , Humans , Insulin-Like Growth Factor II/pharmacology
6.
Meat Sci ; 136: 93-103, 2018 Feb.
Article in English | MEDLINE | ID: mdl-29107868

ABSTRACT

The objective was to compare growth performance, belly characteristics, and bacon slicing yields of growing-finishing pigs fed a subtherapeutic dose of an antibiotic, a natural antimicrobial, or a diet containing no antibiotics or antimicrobials. Barrows and gilts (96 each, initial BW: 27.52±3.98kg) were housed in 48 pens (8 replications per treatment) in a 2×3 factorial randomized complete block design. Pens were assigned 1 of 3 diets: antibiotic free, oregano or tylosin phosphate. Pigs were slaughtered at an average BW of 127.31±10.18kg. There were no differences among dietary treatments for growth performance (P≥0.06), carcass cutability (P≥0.42), loin quality (P≥0.28), fresh belly dimensional characteristics (P≥0.11), IV (P≥0.87) or bacon processing characteristics (P≥0.07). Given the lack of differences in meat quality from pigs fed diets without antibiotics, the implementation of VFD in the United States should not result in changes in pork quality.


Subject(s)
Anti-Infective Agents/pharmacology , Diet/veterinary , Origanum , Red Meat/analysis , Swine/growth & development , Tylosin/analogs & derivatives , Tylosin/pharmacology , Animal Feed/analysis , Animal Nutritional Physiological Phenomena , Animals , Body Composition/drug effects , Female , Male , Plant Oils/pharmacology , Swine/physiology
7.
Demography ; 54(6): 2001-2024, 2017 12.
Article in English | MEDLINE | ID: mdl-29094262

ABSTRACT

We examine inferences about old-age mortality that arise when researchers use survey data matched to death records. We show that even small rates of failure to match respondents can lead to substantial bias in the measurement of mortality rates at older ages. This type of measurement error is consequential for three strands in the demographic literature: (1) the deceleration in mortality rates at old ages; (2) the black-white mortality crossover; and (3) the relatively low rate of old-age mortality among Hispanics, often called the "Hispanic paradox." Using the National Longitudinal Survey of Older Men matched to death records in both the U.S. Vital Statistics system and the Social Security Death Index, we demonstrate that even small rates of missing mortality matching plausibly lead to an appearance of mortality deceleration when none exists and can generate a spurious black-white mortality crossover. We confirm these findings using data from the National Health Interview Survey matched to the U.S. Vital Statistics system, a data set known as the "gold standard" (Cowper et al. 2002) for estimating age-specific mortality. Moreover, with these data, we show that the Hispanic paradox is also plausibly explained by a similar undercount.


Subject(s)
Bias , Black or African American/statistics & numerical data , Death Certificates , Mortality , White People/statistics & numerical data , Age Distribution , Aged, 80 and over , Censuses , Hispanic or Latino/statistics & numerical data , Humans , Longitudinal Studies , Male , Proportional Hazards Models , Reproducibility of Results , United States/epidemiology , Vital Statistics
8.
Popul Stud (Camb) ; 71(3): 281-292, 2017 11.
Article in English | MEDLINE | ID: mdl-28610548

ABSTRACT

Demographers often form estimates by combining information from two data sources-a challenging problem when one or both data sources are incomplete. A classic example entails the construction of death probabilities, which requires death counts for the subpopulations under study and corresponding base population estimates. Approaches typically entail 'back projection', as in Wrigley and Schofield's seminal analysis of historical English data, or 'inverse' or 'forward projection' as used by Lee in his important reanalysis of that work, both published in the 1980s. Our paper shows how forward and backward approaches can be optimally combined, using a generalized method of moments (GMM) framework. We apply the method to the estimation of death probabilities for relatively small subpopulations within the United States (men born 1930-39 by state of birth by birth cohort by race), combining data from vital statistics records and census samples.


Subject(s)
Demography/methods , Mortality/trends , Research Design , Adult , Black or African American , Aged, 80 and over , Censuses , Data Interpretation, Statistical , Humans , Male , Population Dynamics , United States/epidemiology , Vital Statistics , White People
9.
Transl Anim Sci ; 1(4): 607-619, 2017 Dec.
Article in English | MEDLINE | ID: mdl-32704683

ABSTRACT

Rapid assessment of pork quality by packers necessitates using early postmortem (∼1 d) traits as an indication of aged pork quality (∼14 d). Efforts have been made to develop a grading system based on color and marbling of the ventral side of boneless loins. In order for this system to be successful, there must be a correlation between early postmortem quality traits observed by packers and the same traits observed by consumers after aging. However, the strength and direction of those correlations are unclear. It is also unknown if the correlations between early and aged postmortem quality differ between barrows (B) and gilts (G). Therefore, the objectives were to determine correlations between early postmortem loin quality characteristics and aged loin quality characteristics, and determine if those correlations differed between barrows and gilts. Early postmortem (∼1 d) quality traits included: instrumental and subjective color, marbling and firmness, and loin pH on the ventral surface of the loin. Loins were aged until 14 d postmortem in vacuum packages. Aged quality traits included traits evaluated early as well as shear force and cook loss. Correlations were compared between barrows and gilts using a Fisher's z test. Overall, early subjective firmness scores of barrows were greater (P < 0.001) than those of gilts. No other early quality traits differed between sexes. Early pH was correlated with aged pH (r = 0.80 B; 0.75 G), ventral lightness (r = -0.57 B; -0.54 G), ventral yellowness (r = -0.55 B; -0.55 G), subjective ventral color (r = 0.55, B; 0.41 G), and subjective chop color (r = 0.42 B; 0.44 G). Correlations of early pH and aged quality did not differ between sexes. Early lightness was correlated with aged ventral pH (r = -0.56) and subjective color (r = -0.39) in barrows but not gilts (P ≤ 0.04). Early lightness was correlated with aged lightness (r = 0.60 B; 0.51 G) and yellowness (r = 0.49 B; 0.55 G), but was not correlated with to any aged chop quality traits. Early marbling was correlated with ventral color (r = 0.42) in barrows and ventral marbling (r = 0.67 B; 0.66 G) and chop marbling (r = 0.57 B; 0.59 G) in barrows and gilts. In summary, early pH and lightness were correlated with aged quality characteristics and correlations rarely differed between barrows and gilts. Sex does not need to be accounted for when relating early and aged quality characteristics.

10.
J Am Pharm Assoc (2003) ; 57(2): 256-260, 2017.
Article in English | MEDLINE | ID: mdl-27964888

ABSTRACT

OBJECTIVE: The authors draw on their broad experiences in the profession to put forth their assessment of the critical need for all elements of the pharmacy profession to agree upon its core services, and to deliver those services in all pharmacies. And also the need to promote the value of those services to patients, payers, and other providers. SUMMARY: Since the advent of pharmaceutical care, the profession has changed its curricula and its regulations to reflect the value of direct patient care. For many reasons, the practice has not been unified in delivering these services-lack of definition of what constitutes the service, principally. This has led to the "tower of babel" that exists because of the many names given to these patient-care services by various professional organizations, colleges, payers, and government agencies. Lack of inclusion in benefit design with value-based compensation is also recognized as an important barrier for a pharmacist wishing to provide direct patient-care services. CONCLUSION: The authors believe this issue to be critical for the profession, and appeal to JCPP and its member organizations to provide leadership to the various pharmacy associations and colleges to put immediate energy and resources into the definitions, labels, and branding of pharmacy practice. This leadership is essential if the profession's organizations and colleges are to promote the whole of practice and payment for the entirety of services pharmacists provide.


Subject(s)
Patient Care/methods , Pharmaceutical Services/organization & administration , Pharmacists/organization & administration , Pharmacy/organization & administration , Humans , Leadership , Patient Care/trends , Pharmaceutical Services/trends , Pharmacists/trends , Pharmacy/trends , Professional Role , Societies, Pharmaceutical
11.
J Anim Sci ; 94(5): 2172-83, 2016 May.
Article in English | MEDLINE | ID: mdl-27285713

ABSTRACT

Pigs (192 total) were blocked by age and stratified by initial BW (25.75 ± 2.29 kg) into pens (2 barrows and 2 gilts per pen). Within blocks, pens were randomly allotted to treatments in a 2 × 2 factorial arrangement, with 2 diet forms (meal vs. pellet) and 2 distillers' dried grains with solubles (DDGS) inclusion levels (0 vs. 30%). Pigs were weighed at the beginning of the experiment and at the end of each feeding phase (d 35, 70, and 91) and daily feed allotments were recorded. Pigs were slaughtered at the end of the 91-d experiment, and full gastrointestinal (GI) tract and GI tract component weights were recorded immediately following evisceration. Carcass characteristics and meat quality were determined after a 24-h chill. Overall ADG was increased ( < 0.01) 3.2% when pigs were fed pelleted diets rather than meal diets, but there was no effect ( = 0.46) of DDGS inclusion on overall ADG. Overall ADFI of meal-fed pigs fed 30% DDGS was 4.7% greater ( < 0.01) than that of pigs fed 0% DDGS in meal form, but overall ADFI did not differ ( ≥ 0.19) between DDGS inclusion level in pellet-fed pigs (diet form × DDGS inclusion, < 0.01). When fed meal diets, pigs fed 0% DDGS had 2.7% greater ( = 0.02) overall G:F than pigs fed 30% DDGS; however, there was no difference ( = 0.42) in overall G:F between DDGS inclusion levels in pigs fed pelleted diets (diet form × DDGS inclusion, < 0.03). Pigs fed pelleted diets had 2.9% heavier HCW ( = 0.01), 10.4% greater 10th-rib back fat ( = 0.01), and 1.8 percentage units less estimated lean percentage ( = 0.04) than meal-fed pigs. Full GI tracts of pigs fed pelleted diets were 0.33 percentage units less ( = 0.03) of the ending live weight than that of meal-fed pigs due to decreased ( < 0.01) GI tract contents. Inclusion of DDGS increased ( = 0.03) full GI tract weight, large intestine weight ( < 0.01), and GI tract contents ( = 0.02). Severity of parakeratosis of the pars esophagea was greater ( < 0.01) in pellet-fed pigs than in meal-fed pigs, but the magnitude of the difference was likely not great enough to negatively affect drop credit of stomachs. In conclusion, feeding pelleted diets improved growth performance and increased carcass weight and fatness without causing the development of gastric lesions that would reduce the value of the stomach to packers. Furthermore, inclusion of DDGS in diets reduced HCW and dressing percent and increased GI tract and GI tract contents weight but had no effect on gastric lesion development or LM quality.


Subject(s)
Animal Feed/analysis , Body Composition/drug effects , Diet/veterinary , Food Handling/methods , Swine/physiology , Adipose Tissue/metabolism , Animal Nutritional Physiological Phenomena , Animals , Edible Grain , Female , Male , Zea mays
12.
J Anim Sci ; 94(5): 2198-206, 2016 May.
Article in English | MEDLINE | ID: mdl-27285715

ABSTRACT

One hundred ninety-two pigs were blocked by age and stratified by initial BW (25.7 ± 2.3 kg) into pens (2 barrows and 2 gilts/pen), and within blocks, pens were assigned randomly to 1 of 4 treatments in a 2 × 2 factorial arrangement, with main effects of diet form (meal vs. pelleted) and distillers dried grains with solubles (DDGS) inclusion (0% vs. 30%). Pigs were slaughtered after a 91-d feeding trial, and carcasses were fabricated after a 24-h chilling period. Belly dimensions and flop distance were measured, and an adipose tissue sample from each belly was collected for fatty acid analysis. Bacon was manufactured at a commercial processing facility before being returned to the University of Illinois Meat Science Laboratory for further evaluation. Although bellies from pigs fed pelleted diets were 5.3% heavier ( < 0.01) than bellies from meal-fed pigs, belly weight as a percentage of chilled side weight ( = 0.55) and fresh belly dimensions ( ≥ 0.11) were not affected by diet form. Slab bacon weight and cooked yield were greater ( ≤ 0.01) for bellies from pellet-fed than meal-fed pigs. Despite pellet-fed pigs having a 3.1-unit greater iodine value (IV) than meal-fed pigs, there was no effect ( ≥ 0.16) of diet form on commercial bacon slicing yields. Bacon slabs from pellet-fed pigs produced more ( < 0.01) total bacon slices, but 3.1% fewer ( < 0.01) slices per kilogram than slabs from meal fed pigs. Inclusion of 30% DDGS reduced belly thickness ( < 0.001), flop distance ( < 0.001), and initial belly weight ( = 0.04) by 0.32 cm, 4.97 cm, and 2.85, respectively, and increased ( < 0.001) belly fat IV by 7.1 units compared with bellies from pigs fed 0% DDGS. Feeding 0% DDGS produced more ( < 0.01) total bacon slices than feeding 30% DDGS. Distillers dried grains with solubles inclusion had no effect on slice yields ( ≥ 0.14) or slices per kilogram ( = 0.08). Overall, bellies from pellet-fed pigs were heavier and had greater IV but did not differ in commercial slicing yields from meal-fed pigs. Feeding pigs 30% DDGS produced thinner, softer bellies with greater IV, but slicing yields were not different from bellies of pigs fed 0% DDGS. Thus, swine producers can feed pelleted diets, without or with 30% DDGS, without negatively affecting commercial bacon slicing yield.


Subject(s)
Animal Feed/analysis , Diet/veterinary , Meat/standards , Animal Nutritional Physiological Phenomena , Animals , Body Weight , Edible Grain , Fatty Acids , Female , Food Handling/methods , Male , Meat/analysis , Swine/physiology , Zea mays
13.
J Anim Sci ; 94(12): 5144-5154, 2016 Dec.
Article in English | MEDLINE | ID: mdl-28046148

ABSTRACT

The objective was: 1) to characterize the effect of marketing group on fresh and cured ham quality, and 2) to determine which fresh ham traits correlated to cured ham quality traits. Pigs raised in 8 barns representing 2 seasons (hot and cold) and 2 production focuses (lean and quality) were used. Three groups were marketed from each barn. A total of 7,684 carcasses were used for data collection at the abattoir. Every tenth carcass was noted as a select carcass for in-depth ham quality analyses. Leg primal weight and instrumental color were measured on 100% of the population. On the select 10% of the population, hams were fabricated into sub-primal pieces, and 3-piece hams were manufactured to evaluate cured ham quality and processing yield. Data were analyzed as a split-plot design in the MIXED procedure of SAS with production focus as the whole-plot factor, and marketing group as the split-plot factor. Pearson correlation coefficients between fresh and cured ham traits were computed. There were no differences ( ≥ 0.15) in instrumental color or ultimate pH ( ≥ 0.14) among fresh ham muscles from any marketing group. The only exception was the semimembranosus of marketing group 2 was lighter than marketing group 1 ( = 0.03) and the dark portion of the semitendinosus muscle from group 1 was lighter than from group 3 ( = 0.01). There were no differences ( ≥ 0.33) in ultimate pH of fresh ham muscles between production focuses, but several muscles from quality focus pigs were lighter in color than ham muscles from lean focus pigs. The lack of differences in fresh ham quality lead to few differences in cured ham quality. Cured hams from the quality focus pigs had greater lipid content ( < 0.01) than hams from lean focus pigs. Cured lightness values of hams from marketing group 1 and 2 were 1.52 units lighter than hams from marketing group 3 ( 0.01). Overall, marketing group did not impact ham quality. Fresh ham quality was not strongly related to cured ham quality. Some correlations were present between fresh and cured ham traits, but those relationships were likely not strong enough to be used as a sorting tool for fresh hams to generate high quality cured hams.


Subject(s)
Commerce , Food Handling , Meat/standards , Animal Husbandry , Animals , Muscle, Skeletal , Seasons , Swine
14.
J Anim Sci ; 94(12): 5155-5167, 2016 Dec.
Article in English | MEDLINE | ID: mdl-28046183

ABSTRACT

The objective was to characterize the relationship between fresh loin quality with fresh belly or fresh and cured ham quality. Pigs raised in 8 barns representing 2 seasons [cold ( = 4,290) and hot ( = 3,394)] and 2 production focuses [lean ( = 3,627) and quality ( = 4,057)] were used. Carcass characteristics and other meat quality data were collected on 7,684 carcasses. All of the carcasses were evaluated for HCW, LM depth, tenth rib fat depth, leg (ham primal) weight, instrumental color on the gluteus medius and gluteus profundus of the ham face, and subjective loin quality. Instrumental loin color and ultimate pH (≥ 22 h postmortem) were collected on the ventral side of loins along with dimensions and firmness scores of fresh bellies from 50% of the carcasses. Ten percent of the boneless loins and fresh hams were evaluated for slice shear force (SSF) or cured ham characteristics. Correlation coefficients between traits were computed using the CORR procedure of SAS and considered significantly different from 0 at ≤ 0.05. Temperature decline, beginning at 31 min postmortem and concluding at 22 h postmortem, for the longissimus dorsi and semimembranosus muscles were evaluated on 10% of the carcasses. Ultimate loin pH was correlated with dimensional belly characteristics ( ≥ |0.07|; < 0.0001) fresh ham instrumental color ( ≥ |0.03|; ≤ 0.05), and semimembranosus ultimate pH ( = 0.33; < 0.0001). Further, ultimate loin pH was correlated ( ≤ 0.01) with pump retention ( = 0.087) and cooked yield ( = 0.156) of cured hams. Instrumental L*on the ventral surface of the loin was related to L* on both muscles of the ham face ( ≤ 0.0001). Even though significant relationships between the loin, belly, and ham were detected, the variability in belly and ham quality explained by variability in loin quality was poor (≤ 22.09%). Compositional differences between the loin and belly may have contributed to those poor relationships. Additionally, differences in temperature declines during chilling between the loin and ham likely contributed to the weak nature of relationships. Equilibration of longissimus dorsi temperature to ambient cooler temperature occurred at 14 h postmortem ( = 0.0005), yet the semimembranosus had not equilibrated with ambient (equilibration bay) temperature ( < 0.0001) at 22 h postmortem. Using loin quality to draw conclusions about fresh belly and fresh and cured ham quality may be misleading.


Subject(s)
Meat/standards , Animals , Cold Temperature , Food Handling , Male , Muscle, Skeletal/physiology , Swine
15.
J Health Econ ; 44: 1-9, 2015 Dec.
Article in English | MEDLINE | ID: mdl-26340596

ABSTRACT

Many studies link cross-state variation in compulsory schooling laws to early-life educational attainment, thereby providing a plausible way to investigate the causal impact of education on various lifetime outcomes. We use this strategy to estimate the effect of education on older-age mortality of individuals born in the early twentieth century U.S. Our key innovation is to combine U.S. Census data and the complete Vital Statistics records to form precise mortality estimates by sex, birth cohort, and birth state. In turn we find that virtually all of the variation in these mortality rates is captured by cohort effects and state effects alone, making it impossible to reliably tease out any additional impact due to changing educational attainment induced by state-level changes in compulsory schooling.


Subject(s)
Education/legislation & jurisprudence , Educational Status , Mortality/trends , Schools/legislation & jurisprudence , Education/statistics & numerical data , Female , Humans , Male , Mandatory Programs , Regression Analysis , Schools/statistics & numerical data , State Government , United States/epidemiology
16.
Am Econ Rev ; 105(2): 477-503, 2015 Feb.
Article in English | MEDLINE | ID: mdl-26345146

ABSTRACT

The Great Migration-the massive migration of African Americans out of the rural South to largely urban locations in the North, Midwest, and West-was a landmark event in U.S. HISTORY: Our paper shows that this migration increased mortality of African Americans born in the early twentieth century South. This inference comes from an analysis that uses proximity of birthplace to railroad lines as an instrument for migration.

17.
Biotechnol Prog ; 31(5): 1433-41, 2015.
Article in English | MEDLINE | ID: mdl-26179435

ABSTRACT

Pressures for cost-effective new therapies and an increased emphasis on emerging markets require technological advancements and a flexible future manufacturing network for the production of biologic medicines. The safety and efficacy of a product is crucial, and consistent product quality is an essential feature of any therapeutic manufacturing process. The active control of product quality in a typical biologic process is challenging because of measurement lags and nonlinearities present in the system. The current study uses nonlinear model predictive control to maintain a critical product quality attribute at a predetermined value during pilot scale manufacturing operations. This approach to product quality control ensures a more consistent product for patients, enables greater manufacturing efficiency, and eliminates the need for extensive process characterization by providing direct measures of critical product quality attributes for real time release of drug product.


Subject(s)
Antibodies/metabolism , Polysaccharides/chemistry , Animals , CHO Cells , Cricetulus , Humans , Models, Chemical , Nonlinear Dynamics , Pilot Projects , Quality Control
18.
MAbs ; 7(3): 562-70, 2015.
Article in English | MEDLINE | ID: mdl-25898160

ABSTRACT

Accurate measurement and functional characterization of antibody Fc domain N-linked glycans is critical to successful biosimilar development. Here, we describe the application of methods to accurately quantify and characterize the N-linked glycans of 2 IgG1 biosimilars with effector function activity, and show the potential pitfalls of using assays with insufficient resolution. Accurate glycan assessment was combined with glycan enrichment using lectin chromatography or production with glycosylation inhibitors to produce enriched pools of key glycan species for subsequent assessment in cell-based antibody-dependent cell-mediated cytotoxicity and complement-dependent cytotoxicity effector function assays. This work highlights the challenges of developing high-quality biosimilar candidates and the need for modern biotechnology capabilities. These results show that high-quality analytics, combined with sensitive cell-based assays to study in vivo mechanisms of action, is an essential part of biosimilar development.


Subject(s)
Antibodies, Monoclonal/chemistry , Antibody-Dependent Cell Cytotoxicity , Biological Assay , Biosimilar Pharmaceuticals/chemistry , Immunoglobulin G/chemistry , Polysaccharides/chemistry , Cell Line , Humans , Immunoglobulin Fc Fragments/chemistry
19.
Anal Bioanal Chem ; 407(13): 3851-60, 2015 May.
Article in English | MEDLINE | ID: mdl-25795027

ABSTRACT

The development of sensitive techniques to detect sequence variants (SVs), which naturally arise due to DNA mutations and errors in transcription/translation (amino acid misincorporations), has resulted in increased attention to their potential presence in protein-based biologic drugs in recent years. Often, these SVs may be below 0.1%, adding challenges for consistent and accurate detection. Furthermore, the presence of false-positive (FP) signals, a hallmark of SV analysis, requires time-consuming analyst inspection of the data to sort true from erroneous signal. Consequently, gaps in information about the prevalence, type, and impact of SVs in marketed and in-development products are significant. Here, we report the results of a simple, straightforward, and sensitive approach to sequence variant analysis. This strategy employs mixing of two samples of an antibody or protein with the same amino acid sequence in a dilution series followed by subsequent sequence variant analysis. Using automated peptide map analysis software, a quantitative assessment of the levels of SVs in each sample can be made based on the signal derived from the mass spectrometric data. We used this strategy to rapidly detect differences in sequence variants in a monoclonal antibody after a change in process scale, and in a comparison of three mAbs as part of a biosimilar program. This approach is powerful, as true signals can be readily distinguished from FP signal, even at a level well below 0.1%, by using a simple linear regression analysis across the data set with none to minimal inspection of the MS/MS data. Additionally, the data produced from these studies can also be used to make a quantitative assessment of relative levels of product quality attributes. The information provided here extends the published knowledge about SVs and provides context for the discussion around the potential impact of these SVs on product heterogeneity and immunogenicity.


Subject(s)
Algorithms , Amino Acid Substitution , Antibodies, Monoclonal/chemistry , Protein Interaction Mapping/methods , Recombinant Proteins/chemistry , Sequence Analysis, Protein/methods , Amino Acid Sequence , Antibodies, Monoclonal/genetics , Genetic Variation , Molecular Sequence Data , Protein Binding , Recombinant Proteins/genetics
20.
Psychometrika ; 80(3): 727-47, 2015 Sep.
Article in English | MEDLINE | ID: mdl-25231627

ABSTRACT

Plausible values (PVs) are a standard multiple imputation tool for analysis of large education survey data, which measures latent proficiency variables. When latent proficiency is the dependent variable, we reconsider the standard institutionally generated PV methodology and find it applies with greater generality than shown previously. When latent proficiency is an independent variable, we show that the standard institutional PV methodology produces biased inference because the institutional conditioning model places restrictions on the form of the secondary analysts' model. We offer an alternative approach that avoids these biases based on the mixed effects structural equations model of Schofield (Modeling measurement error when using cognitive test scores in social science research. Doctoral dissertation. Department of Statistics and Heinz College of Public Policy. Pittsburgh, PA: Carnegie Mellon University, 2008).


Subject(s)
Models, Statistical , Psychometrics , Algorithms , Humans
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