Rhythmic movements, such as peristaltic contraction, are initiated by output from central pattern generator (CPG) networks in the CNS. These oscillatory networks elicit locomotion in the absence of external sensory or descending inputs, but CPG circuits produce more directed and behaviorally relevant movement via peripheral nervous system (PNS) input. Drosophila melanogaster larval locomotion results from patterned muscle contractions moving stereotypically along the body segments, but without PNS feedback, contraction of body segments is uncoordinated. We have dissected the role of a subset of mechanosensory neurons in the larval PNS, the chordotonal organs (chos), in providing sensory feedback to the locomotor CPG circuit with DIAS (Dynamic Image Analysis System) software. We analyzed mutants carrying cho mutations including atonal, a cho proneural gene, beethoven, a cho cilia class mutant, smetana and touch-insensitive larva B, two axonemal mutants, and 5D10, a weak cho mutant. All cho mutants have defects in gross path morphology compared to controls. These mutants exhibit increased frequency and duration of turning (decision-making) and reduced duration of linear locomotion. Furthermore, cho mutants affect locomotor parameters, including reduced average speed, direction change, and persistence. DIAS analysis of peristaltic waves indicates that mutants exhibit reduced average speed, positive flow and negative flow, and increased stride period. Thus, cho sensilla are major proprioceptive components that underlie touch sensitivity, locomotion, and peristaltic contraction by providing sensory feedback to the locomotor CPG circuit in larvae.R hythmic movements, such as peristaltic contraction, are initiated by output from central pattern generators (CPGs) in the CNS. These oscillatory networks elicit locomotion in the absence of external sensory or descending inputs, but without feedback from the peripheral nervous system (PNS), contraction of body segments is uncoordinated (1-5). The Drosophila peristaltic CPGs form and become active during late embryogenesis and persist throughout larval stages (5-9). Coordinated peristalsis in Drosophila embryos, therefore, relies on output from the preformed CPG circuits as well as sensory feedback from the PNS. Here, we use DIAS (Dynamic Image Analysis System) software (10, 11) to demonstrate that chordotonal organs (chos), type I sense organs of the larval PNS (12, 13), constitute a major feedback mechanism that provides peripheral input to the CPG for normal locomotion.Suster and Bate (5) demonstrated that blocking neurotransmitter release in the entire embryonic PNS with tetanus toxin (TeTx) prevented normal peristalsis during late embryogenesis (14, 15). Interestingly, the peristaltic defects seen in TeTx embryos phenocopied those exhibited in senseless (sens) null mutants (5, 16). DIAS motility software was used to dissect the dysfunctional locomotor parameters of first-instar TeTx and sens larvae and the role of sensory input from the PNS in driving CPGs (5). Wang et ...

Physician‐investigators face the daunting task of enrolling desperate patients into Phase I cancer trials that are not meant to be therapeutic. Patients doggedly regard the trials as therapeutic, and researchers tend to collaborate in their confusion by glossing the trials’ true purposes and noting the occasional benefit that subjects accidentally receive. The disparity between hope and fact must be redressed by degrees, from many angles at once.

In order to facilitate targeted outreach, we sought to identify patient populations with a lower likelihood of returning for breast cancer screening after COVID-19-related imaging center closures. Methods Weekly total screening mammograms performed throughout 2019 (baseline year) and 2020 (COVID-19-impacted year) were compared. Demographic and clinical characteristics, including age, race, ethnicity, breast density, breast cancer history, insurance status, imaging facility type used, and need for interpreter, were compared between patients imaged from March 16 to October 31 in 2019 (baseline cohort) and 2020 (COVID-19-impacted cohort). Census data and an online map service were used to impute socioeconomic variables and calculate travel times for each patient. Logistic regression was used to identify patient characteristics associated with a lower likelihood of returning for screening after COVID-19-related closures. Results The year-over-year cumulative difference in screening mammogram volumes peaked in week 21, with 2962 fewer exams in the COVID-19-impacted year. By week 47, this deficit had reduced by 49.4% to 1498. A lower likelihood of returning for screening after COVID-19-related closures was independently associated with younger age (odds ratio (OR) 0.78, p < 0.001), residence in a higher poverty area (OR 0.991, p = 0.014), lack of health insurance (OR 0.65, p = 0.007), need for an interpreter (OR 0.68, p = 0.029), longer travel time (OR 0.998, p < 0.001), and utilization of mobile mammography services (OR 0.27, p < 0.001). Conclusion Several patient factors are associated with a lower likelihood of returning for screening mammography after COVID-19-related closures. Knowledge of these factors can guide targeted outreach to vulnerable patients to facilitate breast cancer screening.

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