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LIM domain kinases 1 and 2 (LIMK1 and LIMK2) regulate actin dynamics and subsequently key cellular functions such as proliferation and migration. LIMK1 and LIMK2 phosphorylate and inactivate cofilin leading to increased actin polymerization. As a result, LIMK inhibitors are emerging as a promising treatment strategy for certain cancers and neurological disorders. High-quality chemical probes are required if the role of these kinases in health and disease is to be understood. To that end, we report the results of a comparative assessment of 17 reported LIMK1/2 inhibitors in a variety of

Body mass index (BMI) is routinely used for preoperative risk stratification; however, it does not provide a detailed assessment of body composition and intentional weight loss alone may not decrease complications. Sarcopenia-a disorder involving low muscle mass, quality, or performance-has been associated with an increased risk for postoperative complications and is treatable through nutritional supplementation or resistance training. It, counterintuitively, may occur with obesity as "sarcopenic obesity"; however, the prevalence is not widely known. The purpose of this study was to assess the prevalence of sarcopenia and sarcopenic obesity.Patients underwent body composition assessment using multifrequency bioimpedance testing (InBody 770, InBody USA, California). They were classified as sarcopenic based on the appendicular skeletal muscle index and obese by percent body fat. Body composition parameters were compared between obesity or sarcopenia groups and traditional BMI-based obesity definitions.A total of 219 patients underwent body composition assessment. The mean age was 62.1 years, BMI was 34.3 kg/mSarcopenia and sarcopenic obesity were found in nearly 15% of patients. Measures of muscle quantity increased with higher BMI may influence the prevalence of sarcopenia in the morbidly obese, and these patients may require specialized criteria accounting for increased body mass.

Unabated increases in the prevalence of obesity among American adults have disproportionately affected women, Black persons, and Hispanic persons. The purpose of this study was to evaluate for disparity in rates of patient eligibility for primary total hip arthroplasty (THA) and total knee arthroplasty (TKA) based on race and ethnicity and gender by applying commonly used body mass index (BMI) eligibility criteria to two large national databases.We retrospectively reviewed data from the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database for the years 2015-2019 for primary THA and TKA and the National Health and Nutrition Examination Survey (NHANES) from 2011-2018. Designations of race and ethnicity were standardized between cohorts. BMI cutoffs of50 kg/m143,973 NSQIP THA patients, 242,518 NSQIP TKA patients, and 13,255 NHANES participants were analyzed. Female patients were more likely to be ineligible for surgery across all cohorts for all modeled BMI cutoffs (P.001 for all). Black patients had relatively lower rates of eligibility across all cohorts for all modeled BMI cutoffs (P.0001 for all). Hispanic patients had disproportionately lower rates of eligibility only at a BMI cutoff of35 kg/mUsing BMI cutoffs alone to determine the eligibility for primary THA and TKA may disproportionally exclude women, Black persons, and Hispanic persons. These data raise concerns regarding further disparity and restriction of arthroplasty care to vulnerable populations that are already marginalized.Retrospective Cohort Study, Level III.

Obesity is associated with higher rates of adverse outcomes following primary total hip arthroplasty (THA). The purpose of this study is to utilize 3 national databases to develop projections of obesity within the general population and primary THA patients in the United States through 2029.Data from the National Surgical Quality Improvement Program (NSQIP), the Behavior Risk Factor Surveillance System (BRFSS), and the National Health and Nutrition Examination Survey were queried for years 1999-2019. Current Procedural Terminology code 27130 was used to identify primary THA patients in NSQIP. Individuals were categorized according to body mass index (kg/mA total of 8,222,013 individuals were included (7,986,414 BRFSS, 235,599 NSQIP THA). From 2011 to 2019, the prevalence of normal weight and overweight individuals declined in the general population (BRFSS) and in primary THA. Prevalence of obese/morbidly obese individuals increased in the general population from 31% to 36% and in primary THA from 42% to 49%. Projection models estimate that by 2029, 46% of the general population will be obese/morbidly obese and 55% of primary THA will be obese/morbidly obese.By 2029, we estimate ≥55% of primary THA to be obese/morbidly obese. Increased resources dedicated to care pathways and research focused on improving outcomes in obese arthroplasty patients will be necessary as this population continues to grow.Level III, Retrospective Cohort Study.

Demographic characteristics, risk factors, and clinical variables associated with gonorrhea and chlamydial infection in women being treated in emergency departments (EDs) in the United States are incompletely characterized. We used univariable and multivariable regression analyses on 17,411 encounters from women 18 years and older who presented to EDs in northeast Ohio and were tested for gonorrhea or chlamydial infection. There were 1,360 women (7.8%) who had Chlamydia trachomatis infection and 510 (2.9%) who had Neisseria gonorrhoeae infection. Those infected with C. trachomatis or N. gonorrhoeae were younger (23.8 vs. 29.2 years), unmarried (97.7% vs. 90.1%), Black (93.3% vs. 88.0%), infected with Trichomonas vaginalis (39.9% vs. 27.2%), diagnosed with urinary tract infection (15.7% vs. 10.6%), and treated for gonorrhea and chlamydial infection during the ED visit (31.6% vs. 17.4%) (all ps.001). Women infected with C. trachomatis or N. gonorrhoeae had more urine white blood cells (WBCs) (23.9 vs. 16.4 cells per high-power field [HPF]) and leukocyte esterase (1.2+ vs. 0.8+) on urinalysis. They had more WBCs (18.5 vs. 12.4 cells/HPF) and odds of having T. vaginalis infection (12.8% vs. 8.2%) on vaginal wet preparation (all ps.001). Women infected with C. trachomatis were more likely to be younger and not Black; they were less likely to be treated for gonorrhea and chlamydial infection in the ED and to have lower levels of urine WBCs, leukocyte esterase, and blood than those infected with N gonorrhoeae (all ps ≤ .05).

BACKGROUND: Patients often turn to the online resources to learn about orthopedic procedures. As the rate of joint arthroplasty is projected to increase, the corresponding interest in relevant online education material will increase as well. The American Medical Association (AMA) and National Institutes of Health (NIH) recommend that publicly available online health information be written at the 6th grade or lower reading level to be fully understood by the average adult in the United States. Additionally, educational resources should be written such that readers can process key information (understandability) or identify available actions to take (actionability). The purpose of this study was to quantify the readability, understandability, and actionability of online patient educational materials regarding total knee arthroplasty (TKA). METHODS: The most common Google™ search term utilized by the American public was determined to be “knee replacement”. Subsequently two independent online searches (Google.com) were performed. From the top 50 search results, websites were included if directed at educating patients regarding TKA. Non-text websites (audiovisual), articles (news/research/industry), and unrelated resources were excluded. Readability was quantified using the following valid objective algorithms: Flesch-Kincaid Grade-Level (FKGL), Simple Measure of Gobbledygook (SMOG) grade, Coleman-Liau Index (CLI), and Gunning-Fog Index (GFI). PEMAT was utilized to assess understandability and actionability (0-100%; score ≥70% indicates acceptable scoring). The relationship between search rank with FKGL and PEMAT scores was quantified. RESULTS: A total of 34 (68%) unique websites met inclusion criteria. The mean FKGL, SMOG, CLI, and GFI was 11.8±1.6, 11.1±1.2, 11.9±1.4, and 14.7±1.6, respectively. None of the websites scored within the acceptable NIH/AMA recommended reading levels. Mean understandability and actionability scores were 54.9±12.1 and 30.3±22.0. Only 5.9% (n=2) and 9.2% (n=1) of websites met the ≥70% threshold for understandability and actionability. Only 29.4% (n=10) sources used common language and only 26.9% (n=9) properly defined complicated medical terms. Based on website type, the mean understandability scores for academic institution, private practice, and health information publisher websites were 57.2±8.8%, 52.6±11.1%, and 54.3±15.3% (p=0.67). Readability (rho: -0.07; p=0.69), understandability (rho: -0.02; p=0.93), and actionability (rho: -0.22; p=0.23) scores were not associated with Google™ search rank. CONCLUSION: TKA materials scored poorly with respect to readability, understandability, and actionability. None of the resources scored within the recommended AMA/NIH reading levels. Only 5.9% scored adequately on understandability measures. Substantial efforts are needed to improve online resources to optimize patient comprehension and facilitate informed decision-making. Level of Evidence: III

129 protein kinases, selected to represent the diversity of the rice (Oryza sativa) kinome, were cloned and tested for expression in E. coli. 40 of these rice kinases were purified and screened using differential scanning fluorimetry (DSF) against 627 diverse kinase inhibitors, with a range of structures and activities targeting diverse human kinases. 37 active compounds were then tested for their ability to modify primary root development in Arabidopsis. Of these, 14 compounds caused a significant reduction of primary root length and two slightly increased root elongation compared with control plants. Two inhibitory compounds bind to the predicted orthologue of Arabidopsis PSKR1, one of two receptors for PSK, a small sulfated peptide that positively controls root development. Inhibition could not be rescued by the exogenous addition of the PSK peptide, suggesting that chemical treatment may inhibit both PSKR1 and its closely related receptor PSKR2. Of the compounds acting as root growth inhibitors in Arabidopsis, six conferred the same effect in rice. Compound RAF265 (CHIR-265), previously shown to bind the human kinase BRAF (B-Raf proto-oncogene, serine/threonine kinase), also binds to nine highly conserved rice kinases tested. The binding of human and rice kinases to the same compound suggests that human kinase inhibitor sets will be useful for dissecting the function of plant kinases.

SLK (STE20-like kinase) and STK10 (serine/threonine kinase 10) are closely related kinases whose enzymatic activity is linked to the regulation of ezrin, radixin, and moesin function and to the regulation of lymphocyte migration and the cell cycle. We identified a series of 3-anilino-4-arylmaleimides as dual inhibitors of SLK and STK10 with good kinome-wide selectivity. Optimization of this series led to multiple SLK/STK10 inhibitors with nanomolar potency. Crystal structures of exemplar inhibitors bound to SLK and STK10 demonstrated the binding mode of the inhibitors and rationalized their selectivity. Cellular target engagement assays demonstrated the binding of the inhibitors to SLK and STK10 in cells. Further selectivity analyses, including analysis of activity of the reported inhibitors against off-targets in cells, identified compound 31 as the most potent and selective inhibitor of SLK and STK10 yet reported.

Dual-specificity tyrosine-regulated kinase 1A (DYRK1A) regulates the proliferation and differentiation of neuronal progenitor cells during brain development. Consequently, DYRK1A has attracted interest as a target for the treatment of neurodegenerative diseases, including Alzheimer's disease (AD) and Down's syndrome. Recently, the inhibition of DYRK1A has been investigated as a potential treatment for diabetes, while DYRK1A's role as a mediator in the cell cycle has garnered interest in oncologic indications. Structure-activity relationship (SAR) analysis in combination with high-resolution X-ray crystallography leads to a series of pyrazolo[1,5-b]pyridazine inhibitors with excellent ligand efficiencies, good physicochemical properties, and a high degree of selectivity over the kinome. Compound 11 exhibited good permeability and cellular activity without P-glycoprotein liability, extending the utility of 11 in an in vivo setting. These pyrazolo[1,5-b]pyridazines are a viable lead series in the discovery of new therapies for the treatment of diseases linked to DYRK1A function.

Introduction Bartholin gland cysts or abscesses account for many gynecologic visits in the emergency department (ED). Previous smaller studies have suggested a link between Bartholin cysts/abscesses and sexually transmitted infections (STIs), but few studies have involved the ED. Methods We retrospectively identified patients aged 18 years or older seen in 1 ED between January 2012 and March 2017 who had urinalysis and urine culture and/or were tested for gonorrhea, chlamydia, or trichomonas by nucleic acid amplification testing. Univariate and multivariate analyses were used to evaluate associations between Bartholin cysts/abscess and demographics, laboratory findings, and ED diagnoses. Results Data were collected for 75,000 ED patients; 64 patients had a diagnosis of Bartholin cyst or abscess, 40 of whom were also tested for Neisseria gonorrhoeae or Chlamydia trachomatis. Ten percent of patients with a Bartholin cyst/abscess were infected with N gonorrhoeae, compared with 3% of those without a Bartholin cyst/abscess (P = .008). The rates of C trachomatis and Trichomonas vaginalis infections were 13% and 26%, respectively, among patients with a Bartholin cyst/abscess, compared with 8% and 30%, respectively, among those without a Bartholin cyst/abscess (P > .05 for both). On regression analysis, only increased urobilinogen level (β, 0.31; odds ratio, 1.36; 95% CI, 1.11–1.66; P = .003) and infection with N gonorrhoeae (β, 1.69; odds ratio, 5.40; 95% CI, 1.43–20.35; P = .01) were associated with a Bartholin cyst/abscess. Conclusions Clinicians in the ED should consider testing patients with a Bartholin cyst/abscess for gonorrhea.

DNA testing of human bones is performed for identification when there is no remaining soft tissue, which often means the samples are old or environmentally compromised. Under these circumstances, it can be difficult to obtain a STR DNA profile. It is important to recover the highest quantity and quality of DNA for STR typing. This study compared the DNA recovery and STR profiles from five anatomical locations in five femora and five tibiae. These locations include the proximal metaphysis, proximal diaphysis, mid-diaphysis, distal diaphysis, and distal metaphysis. Twenty-five femur samples and 25 tibia samples were analyzed using the Qiagen Investigator Quantiplex Pro RGQ Kit for quantitating the extracted DNA and the Qiagen Investigator 24plex QS Kit for STR DNA typing. The highest DNA recovery of the five regions tested in both the femur and the tibia was from the midshaft diaphysis. The femur samples resulted in a significantly higher DNA recovery than the tibia samples as analyzed using a Kruskal-Wallis test (P = 0.002103). The midshaft diaphysis and distal diaphysis yielded the most complete STR DNA profiles in the femora, while the distal and proximal diaphysis yielded the most complete STR DNA profiles in the tibiae. There was no correlation between the amount of DNA recovered and the completeness of the STR DNA profile produced with low template extracts in this study.

Background In an effort to help combat the COVID-19 pandemic and preserve essential health care resources, starting in mid-March 2020, surgeons have been instructed to only perform essential surgical procedures. The vast majority of hip and knee arthroplasty surgery does not meet the definition of essential surgery. This study estimated the number of arthroplasty procedures that would be canceled because of these important restrictions. Methods The US hip and knee arthroplasty procedure volume projections for 2020 were estimated from four recently published studies. Data from the American Joint Replacement Registry were utilized to determine what percentage of these cases would be considered nonessential surgery. Monthly and weekly estimates of nonessential hip and knee arthroplasty procedures that would have occurred had there not been any restrictions due to COVID-19 were calculated. Results After excluding essential procedures, it was estimated that approximately 30,000 primary and 3000 revision hip and knee arthroplasty procedures will be canceled each week while COVID-19 restrictions regarding nonessential surgery are in place. If only 50% of nonessential cases were actually canceled across the United States, that would still result in the cancellation of 15,001 primary and 1435 revision hip and knee arthroplasty procedures per week while restrictions are in place. Conclusion This study highlights the profound impact COVID-19 is having on our current hip and knee arthroplasty volume. The large number of cases canceled because of COVID-19 translates into major financial losses for health care institutions and may have a profound impact on our patients.

A quick, simple, and high-yield nucleic acid isolation process is crucial for high-quality DNA analysis. The ability of the MicroGEM PDQeX phytoGEM system and Omega Bio-tek E.Z.N.A.® Plant DS Mini kit to extract PCR-ready DNA was evaluated by extracting the forensically relevant "legal high" plant species: Ipomoea purpurea, Artemisia absinthium, Mitragyna speciosa, Datura stramonium, and Papaver somniferum. The plant material was pulverized, processed using the manufacturer's plant protocol for the PDQeX Nucleic Acid Extraction or the manufacturer's protocol for the Omega extraction, quantified using the Invitrogen Qubit 2.0 Fluorometer, and analyzed for amplifiability by PCR using a Qiagen Rotor-Gene Q instrument and published assays. The DNA amplicons for the legal high species produced high-resolution melt curves concordant with the melts observed when DNA was isolated using the Qiagen DNeasy Plant Mini Kit in previous studies.

Working women diagnosed with cancer face difficult decisions about disclosing personal information. A 2017 survey for Cancer and Careers, a non-profit organization assisting cancer patients and survivors with finding and continuing employment, found that women are more likely than men to share their diagnosis with work colleagues, and do so more often to feel supported by co-workers. However, disclosure guidelines for communication about having cancer are difficult to establish, as they may vary widely depending on the individual and the situation. Most research about health self-disclosure has focused on the initial decision to divulge that one has an illness and on the depth of that initial disclosure. The current study was designed to further describe how working women navigate disclosures not only during the initial diagnosis, but throughout treatment and into recovery to gain needed social support. Using the typology of social support and the tenets of Communication Privacy Management Theory, the goal of this study is to share individual narratives of how working women change privacy rules to procure the type of social support needed in each stage of their experience.

This case illustrates the communication processes involved in developing resilience when facing cancer diagnosis and treatment in the workplace. Beyond just the initial decision about whether to share the news of cancer, individuals enact ongoing communication behaviors that may enhance or detract from their ability to build resilience when going through this level of hardship, loss, and trauma. The case describes communication choices made and the dialectics faced by two women during breast cancer treatment in two different workplaces. The five communication processes of Patrice Buzzanell's communication theory of resilience are described in some detail and applied to these cases. The goal is for managers and others in workplace settings to gain a better understanding of ways to communicate that help someone going through a hardship, loss, or trauma build higher resilience and to better understand the communal nature of resilience in organizational settings.

Becoming a caregiver for two elderly parents in a remote rural area with limited internet access while also teaching online increased the author's awareness of students' challenges and interpersonal needs in online educational modalities. She realized how often students' interpersonal needs, as well as teachers' needs, go unmet in the online classroom. Students' messages may be misread when they are reaching out to teachers in attempt to meet their interpersonal needs through the teacher-student relationship. She argues that online teachers would be wise to rely on William Schutz's Fundamental Interpersonal Relations Orientation to inform their interactions with students. Rather than dismissing students' sometimes clumsily sought or expressed needs, responding to their needs as one human being to another creates relationships that retain and strengthen students' resilience. Vulnerability as a teacher and exploration of our shared “humanness” in all roles within higher education leads to a conclusion that calls for more direct interpersonal contact between teachers and students, not less.

Obesity is a well-established risk factor for complications following primary total knee arthroplasty (TKA). The purpose of this study is to utilize 3 national databases to develop projections of obesity within the general population and primary TKA patients in the United States through 2029.Data from the National Surgical Quality Improvement Program (NSQIP), the Behavior Risk Factor Surveillance System (BRFSS), and the National Health and Nutrition Examination Survey were queried for years 1999-2019. Current Procedural Terminology code 27447 was used to identify primary TKA patients in NSQIP. Individuals were categorized according to body mass index (kg/mA total of 8,372,221 individuals were included (7,986,414 BRFSS, 385,807 NSQIP TKA). From 2011 to 2019, the prevalence of normal weight and overweight individuals declined in the general population (BRFSS) and in primary TKA. Prevalence of obese/morbidly obese individuals increased in the general population from 31% to 36% and in primary TKA from 60% to 64%. Projection models estimate that by 2029, 46% of the general population will be obese/morbidly obese and 69% of primary TKA will be obese/morbidly obese.By 2029, we estimate ≥69% of primary TKA to be obese/morbidly obese. Increased resources dedicated to care pathways and research focused on improving outcomes in obese arthroplasty patients will be necessary as this population continues to grow.Level III, Retrospective Cohort Study.

The polymerase chain reaction (PCR) is used to copy DNA in vitro for a variety of applications including amplifying a target DNA, mutating a base, adding tags, and sequencing by synthesis applications. Next-generation sequencing (NGS) is a DNA sequencing technology that has been applied to screening cancer and tissue variants, deep sequencing, and gene expression analysis, and more recently, it has been applied to DNA typing for human identification, estimating age, and detecting and differentiating body fluids. Body fluids are normally identified using color tests, microscopy, and immunochromatographic assays. Pyrosequencing is an NGS approach that has been applied to body fluid analysis. The pyrosequencing assays can detect one or several mixed body fluids by analysis of their tissue-specific differentially methylated regions (tDMRs). Here, the process of designing pyrosequencing primers for forensic biology applications is described.

The polymerase chain reaction (PCR) is used to copy DNA in vitro for a variety of applications including amplifying a target DNA, mutating a base, adding tags, and sequencing by synthesis applications. Next-generation sequencing (NGS) is a DNA sequencing technology that has been applied to screening cancer and tissue variants, deep sequencing, and gene expression analysis, and more recently, it has been applied to DNA typing for human identification, estimating age, and detecting and differentiating body fluids. Body fluids are normally identified using color tests, microscopy, and immunochromatographic assays. Pyrosequencing is an NGS approach that has been applied to body fluid analysis. The pyrosequencing assays can detect one or several mixed body fluids by analysis of their tissue-specific differentially methylated regions (tDMRs). Here, the process of designing pyrosequencing primers for forensic biology applications is described.

Graphical abstract, Kinases are signalling proteins which have proven to be successful targets for the treatment of a variety of diseases, predominantly in cancers. However, only a small proportion of kinases (

Over 20 years after the approval of the first-in-class protein kinase inhibitor imatinib, the biological function of a significant fraction of the human kinome remains poorly understood while most research continues to be focused on few well-validated targets. Given the strong genetic evidence for involvement of many kinases in health and disease, the understudied fraction of the kinome holds a large and unexplored potential for future therapies. Specific chemical probes are indispensable tools to interrogate biology enabling proper preclinical validation of novel kinase targets. In this Perspective, we highlight recent case studies illustrating the development of high-quality chemical probes for less-studied kinases and their application in target validation. We spotlight emerging techniques and approaches employed in the generation of chemical probes for protein kinases and beyond and discuss the associated challenges and opportunities.

Objective The United States is in an obesity epidemic. Obesity has multiple common comorbid conditions, including lower extremity arthritis. We sought to examine the course of treatment for a population with body mass index (BMI) ≥ 40 kg/m2 and osteoarthritis (OA) of the hip or knee. We investigated decision criteria that influenced arthroplasty surgeons to recommend non-operative management versus total joint arthroplasty (TJA). For those patients who ultimately received TJA, we compared outcomes in this population to those with BMI Methods This study retrospectively reviewed 158 new patients with BMI ≥ 40 kg/m2 and moderate/severe OA of the hip or knee. Demographics, comorbidity profiles, and weight loss were compared between groups that underwent TJA and those that did not. The arthroplasty database was used to identify patients who underwent TJA during 2016-2018 (N=1473). Comorbidities, readmissions, surgical site infections, and overall complications were compared between those with BMI ≥ 40 kg/m2 and BMI Results 51.3% of new patients with BMI ≥ 40 kg/m2 and moderate/severe OA did not return for a second clinic visit. Of those who did return, 42.9% eventually underwent surgery. BMI was higher in single-visit patients versus those with multiple (49.5 kg/m2 v 46.3 kg/m2, p Conclusion A majority of patients with BMI ≥ 40 kg/m2 and moderate/advanced OA will be lost to orthopaedic follow-up. A relatively lower BMI indicates a greater chance of retention in care, and ultimately surgery, but does not influence surgeons’ recommendations to continue orthopaedic management. Patients who persist in seeking treatment, lose significant weight, and exhaust non-operative alternatives, may be suitable for TJA despite a BMI ≥ 40 kg/m2, with an overall complication rate of 4.3%. However, only 9% of patients at 2-year follow-up achieved BMI

Artemisia absinthium (wormwood), a common ingredient in absinthe, contains the compound thujone, which is unregulated by the U.S. Drug Enforcement Agency. Thujone can cause an “unregulated legal high” in higher concentrations. The European Union limits thujone from Artemisia species to 35 mg/kg while the U.S. Food and Drug Administration requires less than 10 ppm to be “thujone-free.” However, individuals can smoke or ingest A. absinthium in different forms. This study developed a polymerase chain reaction (PCR) highresolution melt (HRM) assay to detect and identify A. absinthium based on primer specificity, sensitivity, repeatability, and robustness. A triplex assay was performed with three “unregulated legal high” species: Datura stramonium, Merremia tuberosa, and A. absinthium; the PCR HRM assay detected and identified each plant at melt temperatures 77.42+-0.20°C, 83.88+-0.22°C, and 87.77+- 0.15°C, respectively. The primer set developed distinguished A. absinthium from a variety of plant species and was successfully triplexed.

We report the rate of cosmic ray air showers with multiplicities exceeding 15 muon tracks recorded in the NOvA Far Detector between May 2016 and May 2018. The detector is located on the surface under an overburden of 3.6 meters water equivalent. We observe a seasonal dependence in the rate of multiple-muon showers, which varies in magnitude with multiplicity and zenith angle. During this period, the effective atmospheric temperature and surface pressure ranged between 210 K and 230 K and 940 mbar and 990 mbar, respectively; the shower rates are anticorrelated with the variation in the effective temperature. The variations are about 30% larger for the highest multiplicities than the lowest multiplicities and 20% larger for showers near the horizon than vertical showers.