We Want You Back: Uncovering the Effects on In-Person Instructional Operations in Fall 2020.

Postsecondary institutions' responses to COVID-19 are a topic of immediate relevance. Emergent research suggests that partisanship was more strongly linked to institutions offering in-person instruction for Fall 2020 than was COVID-19. Using data from the College Crisis Initiative and a multiple group structural equation modeling approach, we tested the relationships between our outcome of interest (in-person instruction in Fall 2020) and state and county sociopolitical features, state and county COVID-19 rates, and state revenue losses. Our full-sample model suggested that County Political Preferences had the strongest association with in-person instruction, followed by Pandemic Severity and State Sociopolitical Features. Because institutional sectors may be uniquely sensitive to these factors, we tested our models separately on 4-year public, 4-year private, and 2-year public and 2-year private institutions. State Sociopolitical Features were significantly related to in-person instruction for 4-year private and 2-year public institutions but were strongest for 4-year public institutions. For 4-year private and 2-year public institutions, County Political Preferences' effect sizes were 2-3 times stronger than effects from State Sociopolitical Features. Pandemic Severity was significantly, negatively related to in-person instruction for 4-year private and 2-year public institutions-similar in magnitude to State Sociopolitical Features. Our analysis revealed that COVID-19 played a stronger role in determining in-person instruction in Fall 2020 than initial research using less sophisticated methods suggested-and while State Sociopolitical Features may have played a role in the decision, 4-year private and 2-year public institutions were more sensitive to county-level preferences.

Single-track year-round education for improving academic achievement in U.S. K-12 schools: Results of a meta-analysis.

Background: Research shows that over summer break, students forget approximately 1 month of learning in math and reading; furthermore, some studies find that low-income students lose ground relative to peers. Year-round education (YRE) redistributes schooldays to shorten summer. Prior analyses pooled single-track YRE (academic intervention in which all students attend school on a common calendar) and multitrack YRE (fiscal intervention countering overcrowding, in which groups of students attend school on staggered schedules). Search Methods: Systematic search of 22 online databases in summer 2017 yielded 494 de-duplicated results; 81 warranted full-text examination. After applying selection criteria, nine studies met criteria but did not report data that allowed effect size calculation. Thirty studies constituted our analytic sample. Selection Criteria: Studies needed to be of K-12 single-track YRE (not multitrack, not a mix of single- and multitrack, and not a study that did not specify track), with no accompanying extended instructional time. Studies needed to be from 2001 to 2016, include outcome data, and include a comparison group. Data: We extracted 55 math g, 58 reading g, 29 math odds ratio, and 27 reading odds ratio effect sizes. Results: Students at single-track YRE schools show modestly higher achievement in both math and reading-by a magnitude similar to estimates of summer learning loss-but comparable proficiency. Unexpectedly, the effect was no greater for historically disadvantaged students. Math effects may be larger in middle than elementary school, but the reason is unclear. Importantly, studies of schools that shortened summer to the fewest weeks showed the largest effects in both subjects.

Draft Genome Sequence of a Novel Rhabdovirus Isolated from Deinocerites Mosquitoes.

We present a draft genome of a novel rhabdovirus, called Grenada mosquito rhabdovirus 1 (GMRV1), with homology to Wuhan mosquito virus 9 (WMV9) (NCBI reference sequence NC_031303), isolated from Deinocerites mosquitoes. The genome has a length of 14,420 nucleotides and encodes five open reading frames.

Effect of evolocumab on cholesterol synthesis and absorption.

The effects of cholesterol-lowering drugs, including those that reduce cholesterol synthesis (statins) and those that reduce cholesterol absorption (ezetimibe), on cholesterol absorption and synthesis are well understood. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors are a novel class of cholesterol-lowering drugs that robustly reduce LDL-cholesterol (LDL-C), but little is known about their effects on cholesterol absorption and synthesis. We evaluated how treatment with evolocumab, a fully human monoclonal IgG2 antibody to PCSK9, affects markers of cholesterol synthesis and absorption by measuring these markers in patients from an evolocumab clinical trial. At 2 weeks, changes in ß-sitosterol/total cholesterol (TC) from baseline were 4% for placebo, 10% for evolocumab 140 mg (nonsignificant vs. placebo), and 26% for evolocumab 420 mg (P < 0.001 vs. placebo). Changes in campesterol/TC at week 2, relative to baseline between placebo and evolocumab, were all nonsignificant. Evolocumab had a modest effect on markers of cholesterol synthesis. At 2 weeks, changes in desmosterol/TC were 1% for placebo, 7% for evolocumab 140 mg (nonsignificant vs. placebo), and 15% for evolocumab 420 mg (P < 0.01 vs. placebo). Changes from baseline in lathosterol/TC at week 2 between placebo and evolocumab were nonsignificant. These results suggest that evolocumab has a modest effect on cholesterol synthesis and absorption despite significant LDL-C lowering.

Treating Tibia Fractures With Far Cortical Locking Implants.

Compared with conventional plating, the relatively new technology of far cortical locking (FCL) allows for more flexible fixation. Increased flexibility of FCL constructs is thought to better stimulate secondary osteosynthesis and lead to improved healing for certain fracture patterns. We conducted a study to compare healing rates and complications of tibial fractures treated with FCL or standard plating techniques. Twenty-two patients with fractures of the tibia (Orthopaedic Trauma Association 41ABC, 42C, 43C) were included in the study. Twelve tibia fractures were treated with FCL and 10 with standard plating (locking or nonlocking). Mean follow-up was 47 weeks in the FCL group and 41 weeks in the control group. The fracture healing rate was 92% in the FCL group and 100% in the control group (difference not statistically significant). Of note, there were 2 open fractures in the FCL group and 0 in the control group. The groups had similar complication rates. Our study data suggest FCL implants are not inferior to conventional plating techniques. Given that FCL-treated fractures tended to be more complex, the groups' similar fracture healing rates may indicate improved fracture healing with FCL technology, but this possibility requires further investigation.

Effects of hybrid plating with locked and nonlocked screws on the strength of locked plating constructs in the osteoporotic diaphysis.

BACKGROUND: Hybrid plating (HP) may improve fixation strength of locked plating (LP) constructs by combining the use of locked and nonlocked screws within a bone segment. This biomechanical study evaluated whether a hybrid bridge plating construct provides greater fixation strength than an all-locked construct in the osteoporotic diaphysis. METHODS: LP and HP constructs were applied to a validated surrogate of the osteoporotic femoral diaphysis in a bridge plating configuration. In LP constructs, plates were applied with three locking screws on each side of the fracture gap and remained 1 mm elevated. In HP constructs, plates were applied with two conventional screws complemented by a single locked screw on each side of the fracture. Constructs were tested under dynamic loading to failure in bending, torsion, and axial loading to analyze construct strength and failure mechanism in each loading mode. RESULTS: Compared with the LP construct, the HP construct was 7% stronger in bending (p = 0.17), 42% stronger in torsion (p < 0.001), and 7% weaker in axial compression (p = 0.003). In bending, constructs failed by periprosthetic fracture. In torsion, LP constructs failed by screw breakage, and HP constructs failed by periprosthetic fracture or breakage of the locking screw. In axial compression, all constructs failed by screw migration. CONCLUSIONS: HP delivered similar bending strength and higher torsional strength than an all-locked bridge plating construct, while causing only a small decrease in axial strength. It may therefore provide an attractive alternative to an all-locked construct for plate fixation in the osteoporotic diaphysis.

Locked plating of distal femur fractures leads to inconsistent and asymmetric callus formation.

OBJECTIVES: Locked plating constructs may be too stiff to reliably promote secondary bone healing. This study used a novel imaging technique to quantify periosteal callus formation of distal femur fractures stabilized with locking plates. It investigated the effects of cortex-to-plate distance, bridging span, and implant material on periosteal callus formation. DESIGN: Retrospective cohort study. SETTING: One Level I and one Level II trauma center. PATIENTS: Sixty-four consecutive patients with distal femur fractures (AO types 32A, 33A-C) stabilized with periarticular locking plates. INTERVENTION: Osteosynthesis using indirect reduction and bridge plating with periarticular locking plates. MAIN OUTCOME MEASUREMENT: Periosteal callus size on lateral and anteroposterior radiographs. RESULTS: Callus size varied from 0 to 650 mm2. Deficient callus (20 mm2 or less) formed in 52%, 47%, and 37% of fractures at 6, 12, and 24 weeks postsurgery, respectively. Callus formation was asymmetric, whereby the medial cortex had on average 64% more callus (P=0.001) than the anterior or posterior cortices. A longer bridge span correlated minimally with an increased callus size at Week 6 (P=0.02), but no correlation was found at Weeks 12 and 24 postsurgery. Compared with stainless steel plates, titanium plates had 76%, 71%, and 56% more callus at Week 6 (P=0.04), Week 12 (P=0.03), and Week 24 (P=0.09), respectively. CONCLUSIONS: Stabilization of distal femur fractures with periarticular locking plates can cause inconsistent and asymmetric formation of periosteal callus. A larger bridge span only minimally improves callus formation. The more flexible titanium plates enhanced callus formation compared with stainless steel plates.

A computational technique to measure fracture callus in radiographs.

Callus formation occurs in the presence of secondary bone healing and has relevance to the fracture's mechanical environment. An objective image processing algorithm was developed to standardize the quantitative measurement of periosteal callus area in plain radiographs of long bone fractures. Algorithm accuracy and sensitivity were evaluated using surrogate models. For algorithm validation, callus formation on clinical radiographs was measured manually by orthopaedic surgeons and compared to non-clinicians using the algorithm. The algorithm measured the projected area of surrogate calluses with less than 5% error. However, error will increase when analyzing very small areas of callus and when using radiographs with low image resolution (i.e. 100 pixels per inch). The callus size extracted by the algorithm correlated well to the callus size outlined by the surgeons (R2=0.94, p<0.001). Furthermore, compared to clinician results, the algorithm yielded results with five times less inter-observer variance. This computational technique provides a reliable and efficient method to quantify secondary bone healing response.

Does locked plating of periprosthetic supracondylar femur fractures promote bone healing by callus formation? Two cases with opposite outcomes.

Contemporary locking plates promote biological fixation through indirect reduction techniques and by elevating the plate from the bone. They have improved fixation strength in osteoporotic bone. Periarticular locking plates are rapidly being adopted for bridge plating of periprosthetic femur fractures. When these plates are used for indirect reduction and bridge plating osteosynthesis, fracture union occurs by secondary bone healing with callus formation which is stimulated by interfragmentary motion. In two patients with similar periprosthetic femur fractures treated with periarticular locking plates one fracture healed by ample callus formation while the other resulted in a non-union and had no callus formation six months post-operatively. The case, which progressed to secondary bone healing with callus formation, exhibited varus migration as a result of loss of fixation. The non-union case retained stable fixation. The difference in outcome may indicate that callus formation was promoted by interfragmentary motion secondary to loss of fixation. Conversely, in absence of fixation failure, callus formation was suppressed by stable fixation with a stiff locking plate construct which reduced interfragmentary motion. These observations suggest that locked plating constructs should be sufficiently flexible when applied for bridge plating of comminuted fractures to promote callus formation.

A novel method for detecting neutralizing antibodies against therapeutic proteins by measuring gene expression.

The presence of neutralizing antibodies against protein therapeutics is a concern in the biomedical field. Such antibodies not only reduce the efficacy of protein therapeutics, but also impose potential dangers to the patients receiving them. To date, a small number of in vitro cell-based bioassays for detecting neutralizing antibodies against therapeutic proteins have been developed. Most of the existing assays, however, either involve the use of radioactive materials or have limited sensitivities and/or poor specificities. With advances in mRNA profiling and detection techniques, we have established a novel and non-radioactive bioassay system using branched DNA (bDNA) technology for detecting protein-therapeutic neutralizing antibodies in patient serum. Our assay measures the variations of target gene expression that reflect the biologic effect of the therapeutic agent and the capability of the antibodies, if present, to neutralize the therapeutics. Compared with most existing assays, the new assay is more sensitive and specific, and completely eliminates the use of radioactive materials. Application of the new assay system can be widely expanded if new target genes and responding cell lines for other therapeutics are identified or engineered.

Small molecule biaryl FSH receptor agonists. Part 1: Lead discovery via encoded combinatorial synthesis.

High-throughput screening of two million compounds in 37 distinct encoded combinatorial libraries using FSH receptor transfected cells provided small molecule agonists such as 1 (EC(50)=3 microM) and 2 (EC(50)=3.9 microM), based on which a focused combinatorial library with a total of 31372 compounds was designed, synthesized, and screened to reveal 72 novel biaryl FSH receptor agonists such as 8a-c as well as a unique combinatorial SAR.

Small molecule biaryl FSH receptor agonists. Part 2: Lead optimization via parallel synthesis.

Potent small molecule biaryl diketopiperazine FSH receptor agonists such as 10c (EC(50)=13 nM) and 11f (EC(50)=1.2 nM) were discovered through the design, synthesis and evaluation of three biaryl diketopiperazine optimization libraries with over 300 compounds. These libraries were prepared via solid-phase parallel synthesis using a cyclization-release method.

BACE1 (beta-secretase) knockout mice do not acquire compensatory gene expression changes or develop neural lesions over time.

The formation of Alzheimer's Abeta peptide is initiated when the amyloid precursor protein (APP) is cleaved by the enzyme beta-secretase (BACE1); inhibition of this cleavage has been proposed as a means of treating Alzheimer's disease. (AD) We have previously shown that young BACE1 knockout mice (BACE1 KO) do not generate Abeta but in other respects appear normal. Here we have extended this analysis to include both gene expression profiling and phenotypic assessment of older BACE1 KO animals to evaluate the impact of chronic Abeta deficiency. We did not detect global compensatory changes in neural gene expression in young BACE1 KO mice. In particular, expression of the beta-secretase homolog BACE2 was not upregulated. Furthermore, we found no structural alterations in any organ, including all central and peripheral neural tissues, of BACE1 KO mice up to 14 months of age. Aged BACE1 KO mice engineered to overexpress human APP (BACE1 KO/APPtg) did not develop amyloid plaques. These data provide evidence that neither beta-secretase nor Abeta plays a vital role in mouse physiology and that chronic beta-secretase inhibition could be a useful approach in treating AD.