Many critical science, societal, and engineering fields contain large-scale multiobjective optimization problems (LSMOPs), comprised of many decision variables. However, as the number of decision variables increases, optimization algorithms face exponentially large search spaces, thereby exhibiting a degraded performance. Nonetheless, LSMOPs whose optimal solutions correspond to sparse variable vectors can be solved more efficiently by evolutionary multiobjective optimization (EMO) algorithms. Despite the great recent strides in developing generic EMO algorithms for sparse LSMOPs, there is still room for improvement. Specifically, algorithms still struggle to find convergent and diverse Pareto fronts in an acceptable amount of time when solving sparse LSMOPs with thousands of decision variables. To better solve sparse LSMOPs, we propose a novel set of evolutionary operators to adapt small-scale EMO algorithms for sparse LSMOPs. These simple, novel, and effective operators include varied striped sparse population sampling (VSSPS), sparse simulated binary crossover (S-SBX), and sparse polynomial mutation (S-PM). These operators, combined with NSGA-II, make the proposed S-NSGA-II algorithm. S-NSGA-II runs near-universally faster than existing methods for problems containing up to 6,400 decision variables, while performing as well as or better than contemporary sparse LSMOP algorithms with respect to hypervolume, especially with problems with larger than 5,000 decision variables.

Preconception care is the prevention and management of biomedical, behavioral, and social risk factors to improve pregnancy outcomes and overall health for reproductive-age patients. A community-based pharmacist-directed preconception care outreach program was developed for women ages 18-45 years living in a rural maternity care desert to help them identify potential health risks and provide them with the needed education, counseling, or referrals to address these risks. Supervised student pharmacists, pharmacy practice residents, and pharmacy faculty from a local University collaborated to provide this program at four community events in conjunction with a mobile health clinic. A summative evaluation was performed after the events concluded, modeled after the RE-AIM framework. One hundred and forty-one women were served by the outreach program. Nearly 98% reported at least one preconception health risk, and 45% reported a barrier preventing them from being able to have an appointment with a physician in the last year. The outreach program was feasible to implement and can be adapted to different settings. Pharmacist-directed outreach programs in rural communities may benefit patients who are not receiving or do not have access to such care in traditional healthcare settings.

Law – charters, statutes, judicial decisions, and traditions – mattered in colonial America, and laws about religion mattered a lot. The legal history of colonial America reveals that America has been devoted to the free exercise of religion since well before the First Amendment was ratified. Indeed, the two colonies originally most opposed to religious liberty for anyone who did not share their views, Connecticut and Massachusetts, eventually became bastions of it. By focusing on law, Scott Douglas Gerber offers new insights about each of the five English American colonies founded for religious reasons – Maryland, Rhode Island, Pennsylvania, Connecticut, and Massachusetts – and challenges the conventional view that colonial America had a unified religious history.

Chloride intracellular channels (CLICs) are a family of proteins that exist in soluble and transmembrane forms. The newest discovered member of the family CLIC6 is implicated in breast, ovarian, lung gastric, and pancreatic cancers and is also known to interact with dopamine-(D(2)-like) receptors. The soluble structure of the channel has been resolved, but the exact physiological role of CLIC6, biophysical characterization, and the membrane structure remain unknown. Here, we aimed to characterize the biophysical properties of this channel using a patch-clamp approach. To determine the biophysical properties of CLIC6, we expressed CLIC6 in HEK-293cells. On ectopic expression, CLIC6 localizes to the plasma membrane of HEK-293cells. We established the biophysical properties of CLIC6 by using electrophysiological approaches. Using various anions and potassium (K+) solutions, we determined that CLIC6 is more permeable to chloride-(Cl-) as compared to bromide-(Br-), fluoride-(F-), and K+ ions. In the whole-cell configuration, the CLIC6 currents were inhibited after the addition of 10μM of IAA-94 (CLIC-specific blocker). CLIC6 was also found to be regulated by pH and redox potential. We demonstrate that the histidine residue at 648 (H648) in the C terminus and cysteine residue in the N terminus (C487) are directly involved in the pH-induced conformational change and redox regulation of CLIC6, respectively. Using qRT-PCR, we identified that CLIC6 is most abundant in the lung and brain, and we recorded the CLIC6 current in mouse lung epithelial cells. Overall, we have determined the biophysical properties of CLIC6 and established it as a Cl- channel.