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To estimate the changes in infertility from 1995-2019 and determine the association of individual-level characteristics with fertility in the United States.Cross-sectional study.Periodic data from 1995, 2002, 2006-2010, 2011-2013, 2013-2015, 2015-2017, and 2017-2019 cycles of the National Survey for Family Growth were used for this analysis. The National Survey for Family Growth comprises samples of the household-level population of women aged 15-44 years in the United States.Surveyed married and cohabiting women aged 15-44 years.None.The primary outcomes were the rates of infertility across subgroups of married or cohabiting women. For secondary outcomes, we performed bivariable and multivariable logistic regression models using the pooled sample (N = 53,764) to determine the association of individual-level characteristics, including age, parity, pelvic inflammatory disease treatment, education, income, race or ethnicity, and receipt of sexual and reproductive health services, with the odds of 12-month infertility among married or cohabiting women.The fluctuations in infertility over this period, with a low of 5.8% in 2006-2010 and a high of 8.1% in 2017-2019, were not found to be statistically significant. This trend was present across nearly all subgroups. The multivariable model showed that women who were older and nulliparous, had fewer years of education, had lower income, were non-Hispanic black, or were not receiving sexual and reproductive health services were more likely to be infertile.This study confirms that parity, age, race, and education level continue to have an association with infertility. Further, the results demonstrate that access to sexual and reproductive health services plays an important role in infertility. In contrast to previous studies, infertility in the United States is no longer on the decline, and Hispanic ethnicity did not have a significant relationship with infertility. Given the rise of sexually transmitted infections and the persistent lack of access to sexual and reproductive health services, particularly among already vulnerable groups, the connection between access to care and infertility is ripe for further investigation.

Malaria remains a large-scale public health problem, killing more than 400,000 people and infecting up to 230 million worldwide, every year. Unfortunately, despite numerous efforts and research concerning vaccine development, results to date have been low and/or strain-specific. This work describes a strategy involving Plasmodium falciparum Duffy binding-like (DBL) and reticulocyte-binding protein homologue (RH) family-derived minimum functional peptides, netMHCIIpan3.2 parental and modified peptides’ in silico binding prediction and modeling some Aotus major histocompatibility class II (MHCII) molecules based on known human molecules’ structure to understand their differences. These are used to explain peptides’ immunological behaviour when used as vaccine components in the Aotus model. Despite the great similarity between human and Aotus immune system molecules, around 50% of Aotus allele molecules lack a counterpart in the human immune system which could lead to an Aotus-specific vaccine. It was also confirmed that functional Plasmodium falciparum’ conserved proteins are immunologically silent (in both the animal model and in-silico prediction); they must therefore be modified to elicit an appropriate immune response. Some peptides studied here had the desired behaviour and can thus be considered components of a fully-protective antimalarial vaccine.

Description, Pre-Columbian urban center of Tiwanaku in the heights of the Andes hosted people from as far as the jungles of the Amazon., Tiwanaku civilization flourished in the Lake Titicaca basin between 500 and 1000 CE and at its apogee influenced wide areas across the southern Andes. Despite a considerable amount of archaeological data, little is known about the Tiwanaku population. We analyzed 17 low-coverage genomes from individuals dated between 300 and 1500 CE and demonstrated genetic continuity in the Lake Titicaca basin throughout this period, which indicates that the substantial cultural and political changes in the region were not accompanied by large-scale population movements. Conversely, the ritual center of Tiwanaku revealed high diversity, including individuals with primarily local genetic ancestry and those with foreign admixture or provenance from as far as the Amazon. Nonetheless, most human offerings associated with the Akapana platform exhibited pure Titicaca basin ancestry and dated to ca. 950 CE—the onset of Tiwanaku’s decline as a sociopolitical center. Our results strengthen the view of Tiwanaku as a complex and far-reaching polity.

Tiwanaku was a civilization that flourished in the Lake Titicaca Basin (present-day Bolivia) between 500 and 1000 CE. At its apogee, Tiwanaku controlled the lake’s southern shores and influenced certain areas of the Southern Andes. There is a considerable amount of archaeological and anthropological data concerning the Tiwanaku culture; however, our understanding of the population of the site of Tiwanaku is limited. To understand the population dynamics at different stages of the Tiwanaku cultural development, we analyzed 17 low-coverage genomes from individuals dated between 300 and 1500 CE. We found that the population from the Lake Titicaca Basin remained genetically unchanged throughout more than 1200 years, indicating that significant cultural and political changes were not associated with large scale population movements. In contrast, individuals excavated from Tiwanaku’s ritual core were highly heterogeneous, some with genetic ancestry from as far away as the Amazon, supporting the proposition of foreign presence at the site. However, mixed-ancestry individuals’ presence suggests they were local descendants of incomers from afar rather than captives or visiting pilgrims. A number of human offerings from the Akapana Platform dating to ca. 950 CE mark the end of active construction and maintenance of the monumental core and the wane of Tiwanaku culture.Significance StatementTiwanaku was an important pre-Inca polity in South America and an example of primary social complexity on par with civilizations in the Indus and Nile river valley. Flourishing between 500 and 1000 CE, Tiwanaku exercised control in the south Titicaca basin and influenced a vast area in southern Peru, Bolivia, and northern Chile. Comprehensive archeological studies provided information about the rise, expansion, and fall of the Tiwanaku culture, but little is known about the monumental site’s population. To address this lacuna, we generated low coverage genomes for 17 individuals, revealing that while the Titicaca basin’s residential population was homogenous, the individuals excavated from the ritual core of Tiwanaku drew their ancestry from distant regions.

BackgroundAchieving low disease activity (LDA) or remission is a main treatment target in PsA. Composite indices used to assess disease activity include Disease Activity index for PsA (DAPSA) and PsA Disease Activity Score (PASDAS), which both have cut points for the states of remission and LDA. In addition, LDA and remission can be assessed by the pure state instrument Minimal Disease Activity (MDA)/Very Low Disease Activity (VLDA).ObjectivesThese analyses aim to identify overlap and differences between these composite indices in PsA patients treated with upadacitinib (UPA), a Janus kinase inhibitor, or adalimumab (ADA) in the phase 3 SELECT-PsA 1 trial.MethodsIn SELECT-PsA 1 (phase 3, randomized controlled trial, with long-term extension up to 5 years), patients with moderate to severely active PsA with prior inadequate response or intolerance to ≥1 non-biologic DMARD were randomized to oral UPA at doses of 15 mg or 30 mg (once daily), subcutaneous ADA 40 mg (every other week), or placebo.1 LDA was assessed using MDA (threshold: 5/7 criteria), DAPSA (≤14), PASDAS (≤3.2), and Patient Global Assessment of Disease Activity (PtGA; ≤3).2,3 These post-hoc descriptive analyses include 1-year (cut off: week 56) as observed data from UPA 15 mg and ADA.ResultsIn total, 858 patients (UPA 15 mg: n=429; ADA: n=429) were included in these analyses. Patients receiving UPA and ADA were on average 52 years of age, 54% were female, with an average disease duration of approximately 6 years.1 With both UPA and ADA, there was a high degree of overlap in the proportion of patients achieving LDA thresholds in MDA, DAPSA, and PASDAS (Figure 1), with reported PtGA improvements showing a similar trend. Defining LDA according to MDA or respective cut points for DAPSA, PASDAS, or PtGA, the proportion of “non-responders” (ie, patients who did not reach such states) is shown in Figure 2. Of the individual components included in these indices, fewer patients reported low levels of SF-36 Physical Component Summary (SF36-PCS), Patient Assessment of Pain Numeric Rating Scale (Pain NRS), and Health Assessment Questionnaire - Disability Index (HAQ-DI) scores, as well as Tender Joint Count 68 (TJC68), with similar responses observed across all indices.ConclusionIn this post-hoc analysis from the SELECT-PsA 1 trial, there was a high degree of overlap between patients in LDA across the composite indices, including MDA, DAPSA, and PASDAS, irrespective of treatment with UPA 15 mg or ADA and despite variability in inclusion of certain components in some indices but not others. Across all indices, fewer patients reported low levels of SF36-PCS, Pain NRS, and HAQ-DI scores, and TJC68. These data show that improvements in (subjective) “patient-driven” components were the most challenging to achieve. These data indicate a similar pattern of residual disease activity, or influence by residual damage or external factors, regardless of composite endpoint utilized.References[1]McInnes IB et al. N Engl J Med. 2021; 384(13):1227-39[2]Kerschbaumer et al. Baillieres Best Pract Res Clin Rheumatol. 2018; 32:401-14[3]Gorlier et al. Ann Rheum Dis. 2019; 78:201-208AcknowledgementsAbbVie funded these studies and participated in the study design, research, analysis, data collection, interpretation of data, reviewing, and approval of the publication. No honoraria or payments were made for authorship. Medical writing support was provided by Monica R.P. Elmore, PhD of AbbVie.Disclosure of InterestsJosef S. Smolen Consultant of: AbbVie, BMS, Celgene, Chugai, Eli Lilly, Gilead, Janssen, MSD, Novartis-Sandoz, Pfizer, Roche, Samsung, Sanofi, and UCB, Grant/research support from: AbbVie, BMS, Celgene, Chugai, Eli Lilly, Gilead, Janssen, MSD, Novartis-Sandoz, Pfizer, Roche, Samsung, Sanofi, and UCB, Ennio Lubrano Speakers bureau: AbbVie, Celgene, Galapagos, Janssen, MSD, Novartis, and Pfizer, Consultant of: AbbVie, Celgene, Galapagos, Janssen, MSD, Novartis, and Pfizer, Grant/research support from: AbbVie, Celgene, Galapagos, Janssen, MSD, Novartis, and Pfizer, Mitsumasa Kishimoto Speakers bureau: AbbVie, Amgen-Astellas BioPharma, Asahi-Kasei Pharma, Astellas, Ayumi Pharma, BMS, Celgene, Chugai, Daiichi-Sankyo, Eisai, Eli Lilly, Gilead, Janssen, Kyowa Kirin, Novartis, Ono Pharma, Pfizer, Tanabe-Mitsubishi, and UCB, Consultant of: AbbVie, Amgen-Astellas BioPharma, Asahi-Kasei Pharma, Astellas, Ayumi Pharma, BMS, Celgene, Chugai, Daiichi-Sankyo, Eisai, Eli Lilly, Gilead, Janssen, Kyowa Kirin, Novartis, Ono Pharma, Pfizer, Tanabe-Mitsubishi, and UCB, Andra Balanescu Speakers bureau: AbbVie, Amgen, Angellini, Astra-Zeneca, Berlin-Chemie, BMS, MSD, Novartis, Pfizer, Roche, Sandoz, Teva, UCB, and Zentiva, Consultant of: AbbVie, Pfizer, and Ewopharma, Vibeke Strand Consultant of: AbbVie, Amgen, Arena, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Celltrion, Eli Lilly, Genentech/Roche, Gilead, GlaxoSmithKline, Ichnos, Inmedix, Janssen, Kiniksa, Merck, Myriad Genetics, Novartis, Pfizer, Regeneron Pharmaceuticals, Inc., Samsung, Sandoz, Sanofi, Setpoint, and UCB, Tianming Gao Shareholder of: AbbVie Inc., Employee of: AbbVie Inc., Nancy Vranich Shareholder of: AbbVie Inc., Employee of: AbbVie Inc., Ralph Lippe Shareholder of: AbbVie Inc., Employee of: AbbVie Inc., William Tillett Shareholder of: AbbVie Inc., Employee of: AbbVie Inc.

Surface Warfare Officers (SWOs) currently attend Basic Division Officer Courses (BDOC) and Junior Officer of the Deck (JOOD) courses prior to their first Division Officer (DIVO) tour. Due to the commissioning schedule, the schedule of these different courses and the number of seats available, there is typically a large wait time for SWOs during different times of the year between classes and before they enter the fleet. These wait times are costly and lower the military readiness of the fleet. With a growing Naval force, minimizing the friction that SWOs experience can produce more Department Heads in order to man the larger fleet by training more Junior Officers today. Current analysis is done in Excel and calculations must be repeated for different scenarios. These scenarios include different arrival rates and distributions, service rates, and population sizes. Using Simio and Python, simulation models of a queuing network can be created in order to find different queue lengths and waiting times automatically using historic commissioning rates and schedules. Once a proof-of-concept model has been created, the model inputs can be changed to match predicted inputs for a growing Naval force. Then allocations of training schedules and capacities can be recommended in order to optimize the SWO training pipeline. Lieutenant, United States Navy Approved for public release. distribution is unlimited

This paper revives a fascinating debate: did a drought start before, during, or after the collapse of the Andean polity of Tiwanaku? Here we present an alternate age model that highlights the real issue: the data from Lake Orurillo, no matter the age model, are too imprecise to address the question. The authors neglect the significance of four-century error ranges (95% probability) for a drought that lasted a single century, according to their estimates. They are content to treat an imprecise correlation between drought and collapse as a causal relationship. Future efforts will require much greater attention to refining both paleoclimate and cultural chronologies, which is a necessary first step in understanding complex episodes of human–environment interaction.

Like Thomas Hardy's famous novel Far from the Madding Crowd, Plasmodium falciparum parasites display their most relevant survival structures (proteins) involved in host cell invasion far away from the immune system's susceptible regions, displaying tremendous genetic variability, to attract the immune response and escape immune pressure. The 3D structure localisation of the conserved amino acid sequences of this deadly parasite's most relevant proteins involved in host cell invasion, as well as the location of the highly polymorphic, highly immunogenic regions, clearly demonstrates that such structures are far apart, sometimes 90&#176, to 180&#176, opposite, thereby rendering the immune response useless. It is also shown here that these conserved, functionally-relevant structures are immunologically silent, since no immune response has been induce