At What Cost to Clinical Trial Enrollment? A Retrospective Study of Patient Travel Burden in Cancer Clinical Trials.

BACKGROUND: Recent literature suggests that living in a rural setting may be associated with adverse cancer outcomes. This study examines the burden of travel from home to cancer center for clinical trial (CT) enrollees. MATERIALS AND METHODS: Patients from the University of California San Francisco Clinical Trial Management System database who enrolled in a cancer CT for a breast, genitourinary, or gastrointestinal malignancy between 1993 and 2014 were included. Cancer type, household zip code, race/ethnicity, phase of study, study sponsor, and year of signed consent were exported. Distance traveled from home to center was calculated using a GoogleMaps application programming interface. The relationships of distance with phase of CT, household income, and race/ethnicity were examined. RESULTS: A total of 1,600 patients were enrolled in breast (55.8%), genitourinary (29.4%), or gastrointestinal (14.9%) cancer CTs. The overall median unidirectional distance traveled from home to study site was 25.8 miles (interquartile range [IQR] 11.5-75.3). Of the trial sponsors examined, principal investigator (56.4%), industry (22.2%), cooperative group (11.6%), and National Institutes of Health (NIH; 9.8%), the longest distance traveled was for NIH-sponsored trials, with a median of 39.4 miles (p < .001). Phase I (8.4%) studies had the longest distance traveled, with a median of 41.2 miles (IQR 14.5-101.0 miles; p = .001). White patients (83%) traveled longer compared with black patients (4.4%), with median distances of 29.9 and 13.9 miles, respectively (p < .001). Patients from lower-income areas (n = 799) traveled longer distances compared with patients from higher-income areas (n = 773; 58.3 vs. 17.8 miles, respectively; p < .001). A multivariable linear model where log10 (distance) was the outcome and adjusting for the exported variables and income revealed that cancer type, year of consent, race/ethnicity, and income were significantly associated with distance traveled. CONCLUSION: This study found that the burden of travel is highest among patients enrolled in NIH-sponsored trials, phase I studies, or living in low-income areas. These data suggest that travel burden for cancer CT participants may be significant. IMPLICATIONS FOR PRACTICE: This study is one of the first to measure travel distance for patients in cancer clinical trials using a real-world GoogleMaps calculator. Out-of-pocket expenses such as travel are not typically covered by health care payers; therefore, patients may face considerable cost to attend each study visit. Using a single-center clinical trials enrollment database, this study found that the burden of travel is highest for patients enrolled in National Institutes of Health-sponsored trials and phase I studies, as well as for patients living in low-income areas. Results suggest that a significant proportion of patients enrolled in clinical trials face a substantial travel burden.

A Phase II Trial of Selinexor, an Oral Selective Inhibitor of Nuclear Export Compound, in Abiraterone- and/or Enzalutamide-Refractory Metastatic Castration-Resistant Prostate Cancer.

LESSONS LEARNED: In abiraterone- and/or enzalutamide-refractory metastatic castration-resistant prostate cancer (mCRPC) patients, selinexor led to prostate-specific antigen and/or radiographic responses in a subset of patients, indicating clinical activity in this indication.Despite twice-a-week dosing and maximal symptomatic management, selinexor was associated with significant anorexia, nausea, and fatigue in mCRPC patients refractory to second-generation anti-androgen therapies, limiting further clinical development in this patient population.This study highlights the challenge of primary endpoint selection for phase II studies in the post-abiraterone and/or post-enzalutamide mCRPC space. BACKGROUND: Selinexor is a first-in-class selective inhibitor of nuclear export compound that specifically inhibits the nuclear export protein Exportin-1 (XPO-1), leading to nuclear accumulation of tumor suppressor proteins. METHODS: This phase II study evaluated the efficacy and tolerability of selinexor in patients with metastatic castration-resistant prostate cancer (mCRPC) refractory to abiraterone and/or enzalutamide. RESULTS: Fourteen patients were enrolled. Selinexor was initially administered at 65 mg/m2 twice a week (days 1 and 3) and was subsequently reduced to 60 mg flat dose twice a week (days 1 and 3), 3 weeks on, 1 week off, to improve tolerability. The median treatment duration was 13 weeks. At a median follow-up of 4 months, two patients (14%) had ≥50% prostate-specific antigen (PSA) decline, and seven patients (50%) had any PSA decline. Of eight patients with measurable disease at baseline, two (25%) had a partial response and four (50%) had stable disease as their best radiographic response. Five patients (36%) experienced serious adverse events (SAEs; all unrelated to selinexor), and five patients (36%) experienced treatment-related grade 3-4 AEs. The most common drug-related adverse events (AEs) of any severity were anorexia, nausea, weight loss, fatigue, and thrombocytopenia. Three patients (21%) came off study for unacceptable tolerability. CONCLUSION: Selinexor demonstrated clinical activity and poor tolerability in mCRPC patients refractory to second-line anti-androgenic agents.

Detection of ESKAPE Bacterial Pathogens at the Point of Care Using Isothermal DNA-Based Assays in a Portable Degas-Actuated Microfluidic Diagnostic Assay Platform.

An estimated 1.5 billion microbial infections occur globally each year and result in ∼4.6 million deaths. A technology gap associated with commercially available diagnostic tests in remote and underdeveloped regions prevents timely pathogen identification for effective antibiotic chemotherapies for infected patients. The result is a trial-and-error approach that is limited in effectiveness, increases risk for patients while contributing to antimicrobial drug resistance, and reduces the lifetime of antibiotics. This paper addresses this important diagnostic technology gap by describing a low-cost, portable, rapid, and easy-to-use microfluidic cartridge-based system for detecting the ESKAPE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp.) bacterial pathogens that are most commonly associated with antibiotic resistance. The point-of-care molecular diagnostic system consists of a vacuum-degassed microfluidic cartridge preloaded with lyophilized recombinase polymerase amplification (RPA) assays and a small portable battery-powered electronic incubator/reader. The isothermal RPA assays detect the targeted ESKAPE pathogens with high sensitivity (e.g., a limit of detection of ∼10 nucleic acid molecules) that is comparable to that of current PCR-based assays, and they offer advantages in power consumption, engineering, and robustness, which are three critical elements required for the point-of-care setting. IMPORTANCE: This paper describes a portable system for rapidly identifying bacteria in resource-limited environments; we highlight the capabilities of the technology by detecting different pathogens within the ESKAPE collection, which cause nosocomial infections. The system is designed around isothermal DNA-based assays housed within an autonomous plastic cartridge that are designed with the end user in mind, who may have limited technological training. Displaying excellent sensitivity and specificity, the assay systems that we demonstrate may enable future diagnoses of bacterial infection to guide the development of effective chemotherapies and may have a role in areas beyond health where rapid detection is valuable, including in industrial processing and manufacturing, food security, agriculture, and water quality testing.

No effect of juvenile hormone on task performance in a bumblebee (Bombus terrestris) supports an evolutionary link between endocrine signaling and social complexity.

A hallmark of insect societies is a division of labor among workers specializing in different tasks. In bumblebees the division of labor is related to body size; relatively small workers are more likely to stay inside the nest and tend ("nurse") brood, whereas their larger sisters are more likely to forage. Despite their ecological and economic importance, very little is known about the endocrine regulation of division of labor in bumblebees. We studied the influence of juvenile hormone (JH) on task performance in the bumblebee Bombus terrestris. We first used a radioimmunoassay to measure circulating JH titers in workers specializing in nursing and foraging activities. Next, we developed new protocols for manipulating JH titers by combining a size-adjusted topical treatment with the allatotoxin Precocene-I and replacement therapy with JH-III. Finally, we used this protocol to test the influence of JH on task performance. JH levels were either similar for nurses and foragers (three colonies), or higher in nurses (two colonies). Nurses had better developed ovaries and JH levels were typically positively correlated with ovarian state. Manipulation of JH titers influenced ovarian development and wax secretion, consistent with earlier allatectomy studies. These manipulations however, did not affect nursing or foraging activity, or the likelihood to specialize in nursing or foraging activity. These findings contrast with honeybees in which JH influences age-related division of labor but not adult female fertility. Thus, the evolution of complex societies in bees was associated with modifications in the way JH influences social behavior.

Trabecular thickening on mammography post-COVID vaccine and RSV vaccine: Case report.

Ipsilateral axillary adenopathy post-COVID mRNA vaccine has been widely reported and guidelines for management have been established. Isolated changes of axillary tail trabecular thickening without associated adenopathy in the breast present a diagnostic dilemma and no official guidelines have thus far been reported. This finding has been reported after COVID mRNA vaccine and has never been reported with any other vaccine. We report on a patient with such changes on screening mammography 1.5 months after the fifth dose of a COVID-mRNA vaccine and 1 week after RSV vaccine. This raises the possibility that such changes can be seen with vaccines other than the COVID mRNA series of vaccines. The main differential diagnosis includes mastitis and inflammatory breast cancer. The transient nature of this finding with spontaneous resolution at diagnostic mammography and the vaccination history helps to establish the diagnosis and exclude breast cancer.

Down-regulation of honey bee IRS gene biases behavior toward food rich in protein.

Food choice and eating behavior affect health and longevity. Large-scale research efforts aim to understand the molecular and social/behavioral mechanisms of energy homeostasis, body weight, and food intake. Honey bees (Apis mellifera) could provide a model for these studies since individuals vary in food-related behavior and social factors can be controlled. Here, we examine a potential role of peripheral insulin receptor substrate (IRS) expression in honey bee foraging behavior. IRS is central to cellular nutrient sensing through transduction of insulin/insulin-like signals (IIS). By reducing peripheral IRS gene expression and IRS protein amount with the use of RNA interference (RNAi), we demonstrate that IRS influences foraging choice in two standard strains selected for different food-hoarding behavior. Compared with controls, IRS knockdowns bias their foraging effort toward protein (pollen) rather than toward carbohydrate (nectar) sources. Through control experiments, we establish that IRS does not influence the bees' sucrose sensory response, a modality that is generally associated with food-related behavior and specifically correlated with the foraging preference of honey bees. These results reveal a new affector pathway of honey bee social foraging, and suggest that IRS expressed in peripheral tissue can modulate an insect's foraging choice between protein and carbohydrate sources.

Comparing Outcomes of CT-Guided Percutaneous Pericardial Drainage with Surgical Pericardial Window in Patients with Symptomatic Pericardial Effusions.

RATIONALE AND OBJECTIVES: To compare short-term outcomes of CT-guided percutaneous pericardial drainage (PPD) versus subxiphoid surgical pericardial window (PW) drainage and analyze the risk factors associated with their outcomes. MATERIALS AND METHODS: A retrospective chart review of patients who underwent either percutaneous drainage with drainage catheter placement or PW with surgical drain placement for symptomatic pericardial effusion between January 1, 2006 and August 31, 2016 was performed after institutional review board approval (decision number 16-783). The primary objective was to test for associations between the short-term (≤30 days post procedure) complication and recurrence rates in patients with symptomatic pericardial effusions. The secondary objectives were to test for associations between short-term complications with changes in vital signs. RESULTS: Of the 257 procedures included in the final analysis, 142 were in the percutaneous drainage group. Short-term complication rate was significantly greater (p < 0.001) in patients undergoing PW, 17% (19/114), as compared with PPD, 2% (3/142). The estimated odds of having complications in the PW cohort was 9 times greater than the percutaneous drainage cohort (OR = 9.3, 95% CI:  2.7-32.3). No significant difference was observed between whether or not a patient experienced a short-term recurrence and any of the explanatory variables (patient demographics, imaging, and vital signs). CONCLUSION: CT-guided PPD is a safer alternative to surgical PW as it leads to fewer complications without a significant difference in recurrence rate of pericardial effusion.

A molecular half-wave rectifier.

This paper describes the performance of junctions based on self-assembled monolayers (SAMs) as the functional element of a half-wave rectifier (a simple circuit that converts, or rectifies, an alternating current (AC) signal to a direct current (DC) signal). Junctions with SAMs of 11-(ferrocenyl)-1-undecanethiol or 11-(biferrocenyl)-1-undecanethiol on ultraflat, template-stripped Ag (Ag(TS)) bottom electrodes, and contacted by top electrodes of eutectic indium-gallium (EGaIn), rectified AC signals, while similar junctions based on SAMs of 1-undecanethiol-SAMs lacking the ferrocenyl terminal group-did not. SAMs in these AC circuits (operating at 50 Hz) remain stable over a larger window of applied bias than in DC circuits. AC measurements, therefore, can investigate charge transport in SAM-based junctions at magnitudes of bias inaccessible to DC measurements. For junctions with SAMs of alkanethiols, combining the results from AC and DC measurements identifies two regimes of bias with different mechanisms of charge transport: (i) low bias (|V| < 1.3 V), at which direct tunneling dominates, and (ii) high bias (|V| > 1.3 V), at which Fowler-Nordheim (FN) tunneling dominates. For junctions with SAMs terminated by Fc moieties, the transition to FN tunneling occurs at |V| ≈ 2.0 V. Furthermore, at sufficient forward bias (V > 0.5 V), hopping makes a significant contribution to charge transport and occurs in series with direct tunneling (V ≲ 2.0 V) until FN tunneling activates (V ≳ 2.0 V). Thus, for Fc-terminated SAMs at forward bias, three regimes are apparent: (i) direct tunneling (V = 0-0.5 V), (ii) hopping plus direct tunneling (V ≈ 0.5-2.0 V), and (iii) FN tunneling (V ≳ 2.0 V). Since hopping does not occur at reverse bias, only two regimes are present over the measured range of reverse bias. This difference in the mechanisms of charge transport at forward and reverse bias for junctions with Fc moieties resulted in large rectification ratios (R > 100) and enabled half-wave rectification.

Cofabrication: a strategy for building multicomponent microsystems.

This Account describes a strategy for fabricating multicomponent microsystems in which the structures of essentially all of the components are formed in a single step of micromolding. This strategy, which we call "cofabrication", is an alternative to multilayer microfabrication, in which multiple layers of components are sequentially aligned ("registered") and deposited on a substrate by photolithography. Cofabrication has several characteristics that make it an especially useful approach for building multicomponent microsystems. It rapidly and inexpensively generates correctly aligned components (for example, wires, heaters, magnetic field generators, optical waveguides, and microfluidic channels) over very large surface areas. By avoiding registration, the technique does not impose on substrates the size limitations of common registrations tools, such as steppers and contact aligners. We have demonstrated multicomponent microsystems with surface areas exceeding 100 cm(2), but in principle, device size is only limited by the requirements of generating the original master. In addition, cofabrication can serve as a low-cost strategy for building microsystems. The technique is amenable to a variety of laboratory settings and uses fabrication tools that are less expensive than those used for multistep microfabrication. Moreover, the process requires only small amounts of solvent and photoresist, a costly chemical required for photolithography; in cofabrication, photoresist is applied and developed only once to produce a master, which is then used to produce multiple copies of molds containing the microfluidic channels. From a broad perspective, cofabrication represents a new processing paradigm in which the exterior (or shell) of the desired structures are produced before the interior (or core). This approach, generating the insulation or packaging structure first and injecting materials that provide function in channels in liquid phase, makes it possible to design and build microsystems with component materials that cannot be easily manipulated conventionally (such as solid materials with low melting points, liquid metals, liquid crystals, fused salts, foams, emulsions, gases, polymers, biomaterials, and fragile organics). Moreover, materials can be altered, removed, or replaced after the manufacturing stage. For example, cofabrication allows one to build devices in which a liquid flows through the device during use, or is replaced after use. Metal wires can be melted and reset by heating (in principle, repairing a break). This method leads to certain kinds of structures, such as integrated metallic wires with large cross-sectional areas or optical waveguides aligned in the same plane as microfluidic channels, that would be difficult or impossible to make with techniques such as sputter deposition or evaporation. This Account outlines the strategy of cofabrication and describes several applications. Specifically, we highlight cofabricated systems that combine microfluidics with (i) electrical wires for microheaters, electromagnets, and organic electrodes, (ii) fluidic optical components, such as optical waveguides, lenses, and light sources, (iii) gels for biological cell cultures, and (iv) droplets for compartmentalized chemical reactions, such as protein crystallization.

Using prediction markets to predict the outcomes in the Defense Advanced Research Projects Agency's next-generation social science programme.

There is evidence that prediction markets are useful tools to aggregate information on researchers' beliefs about scientific results including the outcome of replications. In this study, we use prediction markets to forecast the results of novel experimental designs that test established theories. We set up prediction markets for hypotheses tested in the Defense Advanced Research Projects Agency's (DARPA) Next Generation Social Science (NGS2) programme. Researchers were invited to bet on whether 22 hypotheses would be supported or not. We define support as a test result in the same direction as hypothesized, with a Bayes factor of at least 10 (i.e. a likelihood of the observed data being consistent with the tested hypothesis that is at least 10 times greater compared with the null hypothesis). In addition to betting on this binary outcome, we asked participants to bet on the expected effect size (in Cohen's d) for each hypothesis. Our goal was to recruit at least 50 participants that signed up to participate in these markets. While this was the case, only 39 participants ended up actually trading. Participants also completed a survey on both the binary result and the effect size. We find that neither prediction markets nor surveys performed well in predicting outcomes for NGS2.

Thin, lightweight, foldable thermochromic displays on paper.

This article describes an electronic display that is fabricated by patterning electrically conductive wires (heaters) with micron-scale dimensions on one side of a sheet of paper, and thermochromic ink on the opposite side. Passing electrical current through the wires heats the paper and changes the thermochromic ink from colored (black, green, or other colors) to transparent; this change in property reveals the paper underneath the ink-exposing any messages printed on the paper-and serves as the basis for a two-state "shutter" display. This type of display is thin (100 microm), flat, lightweight (the display weighs <20 mg/cm(2)), can be folded, rolled, twisted, and creased while maintaining function, and ultimately can (if required) be disposed of by incineration. The display is appropriate for applications where information must be presented clearly (usually only once) for little cost (each display costs <$0.10/m(2) in materials) and where limited electrical power is available.

Quantifying colorimetric assays in paper-based microfluidic devices by measuring the transmission of light through paper.

This article describes a point-of-care (POC) system--comprising a microfluidic, paper-based analytical device (micro-PAD) and a hand-held optical colorimeter--for quantifying the concentration of analytes in biological fluids. The micro-PAD runs colorimetric assays, and consists of paper that has been (i) patterned to expose isolated regions of hydrophilic zones and (ii) wet with an index-matching fluid (e.g., vegetable oil) that is applied using a disposable, plastic sleeve encasement. Measuring transmittance through paper represents a new method of quantitative detection that expands the potential functionality of micro-PADs. This prototype transmittance colorimeter is inexpensive, rugged, and fully self-contained, and thus potentially attractive for use in resource-limited environments and developing countries.

A bilingual, Internet-based, targeted advertising campaign for prostate cancer clinical trials: Assessing the feasibility, acceptability, and efficacy of a novel recruitment strategy.

BACKGROUND: To address limitations in recruitment and enrollment of diverse, low-literacy patients into prostate cancer clinical trials, we evaluated the feasibility, acceptability, and efficacy of an English and Spanish, Internet-based, multilevel recruitment intervention. METHODS: Intervention components included (1) a low-literacy, bilingual, automated, Internet-based clinical trial matching tool; (2) a bilingual nurse who assisted individuals with questions and enrollment; and (3) a targeted, Internet-based advertising campaign. We evaluated (a) completion of matching tool, (b) expression of interest in a clinical trial, (c) number of patients who matched to clinical trials at a single institution, (d) discussion of risks and benefits of clinical trials (via follow-up interviews), and (e) effect of the advertising on completing the matching tool. Feasibility, acceptability, and preliminary estimates of efficacy were measured through user engagement with the matching tool and subsequent qualitative interviews with these same users. RESULTS: During the 28-week study period, 523 users provided demographic information, 263 were identified with prostate cancer, 192 (73%) matched to at least one clinical trial, and 29 (15.1%) of those who matched provided contact information. During the study period, 17 prostate cancer clinical trials were available for matching. We completed follow-up interviews with 14 of the 29 men who provided contact information. Of the 14, 85.7% discussed the risks and benefits of clinical trials with their physician, and 35.7% enrolled in a clinical trial. The Internet-based advertising campaign resulted in an increased number of matching tool completions. CONCLUSIONS: Our study demonstrates that an Internet-based clinical trial matching tool that is advertised using a targeted Internet-based campaign can provide an effective means to reach diverse, low-literacy patients. When implemented at scale and over a longer duration, such interventions may help increase trial participation among underrepresented populations.

Pumping fluids in microfluidic systems using the elastic deformation of poly(dimethylsiloxane).

This paper demonstrates a methodology for storing and pumping fluids that provide a useful capability for microfluidic devices. It uses microfluidic screw valves to isolate fluids in poly(dimethylsiloxane) (PDMS) microcompartments, in which the pressure of the liquid is stored in the elastic deformation of the walls and ceiling of the compartments. Fluids can be stored under pressure in these structures for months. When the valves are opened, the walls and ceiling push the fluid out of the compartments into microfluidic channels. The system has five useful characteristics: (i) it is made using soft lithographic techniques; (ii) it allows multiple reagents to be preloaded in devices and stored under pressure without any additional user intervention; (iii) it makes it possible to meter out fluids in devices, and to control rates of flow of fluids; (iv) it prevents the user from exposure to potentially toxic reagents; and (v) it is hand-operated and does not require additional equipment or resources.

The force acting on a superparamagnetic bead due to an applied magnetic field.

This paper describes a model of the motion of superparamagnetic beads in a microfluidic channel under the influence of a weak magnetic field produced by an electric current passing through a coplanar metal wire. The model based on the conventional expression for the magnetic force experienced by a superparamagnetic bead (suspended in a biologically relevant medium) and the parameters provided by the manufacturer failed to match the experimental data. To fit the data to the model, it was necessary to modify the conventional expression for the force to account for the non-zero initial magnetization of the beads, and to use the initial magnetization and the magnetic susceptibility of the beads as adjustable parameters. The best-fit value of susceptibility deviated significantly from the value provided by the manufacturer, but was in good agreement with the value computed using the magnetization curves measured independently for the beads from the same vial as those used in the experiment. The results of this study will be useful to researchers who need an accurate prediction of the behavior of superparamagnetic beads in aqueous suspensions under the influence of weak magnetic fields. The derivation of the force on a magnetic bead due to a magnetic field also identifies the correct treatment to use for this interaction, and resolves discrepancies present throughout the literature.

Gonadotropic and physiological functions of juvenile hormone in Bumblebee (Bombus terrestris) workers.

The evolution of advanced sociality in bees is associated with apparent modifications in juvenile hormone (JH) signaling. By contrast to most insects in which JH is a gonadotropin regulating female fertility, in the highly eusocial honey bee (Apis mellifera) JH has lost its gonadotrophic function in adult females, and instead regulates age-related division of labor among worker bees. In order to shed light on the evolution of JH signaling in bees we performed allatectomy and replacement therapies to manipulate JH levels in workers of the "primitively eusocial" bumblebee Bombus terrestris. Allatectomized worker bees showed remarkable reduction in ovarian development, egg laying, Vitellogenin and Krüppel homolog 1 fat body transcript levels, hemolymph Vitellogenin protein abundance, wax secretion, and egg-cell construction. These effects were reverted, at least partially, by treating allatectomized bees with JH-III, the natural JH of bees. Allatectomy also affected the amount of ester component in Dufour's gland secretion, which is thought to convey a social signal relating to worker fertility. These findings provide a strong support for the hypothesis that in contrast to honey bees, JH is a gonadotropin in bumblebees and lend credence to the hypothesis that the evolution of advanced eusociality in honey bees was associated with major modifications in JH signaling.

In-hive patterns of temporal polyethism in strains of honey bees (Apis mellifera) with distinct genetic backgrounds.

Honey bee workers exhibit an age-based division of labor (temporal polyethism, DOL). Younger bees transition through sets of tasks within the nest; older bees forage outside. Components of temporal polyethism remain unrevealed. Here, we investigate the timing and pattern of pre-foraging behavior in distinct strains of bees to (1) determine if a general pattern of temporal DOL exists in honey bees, (2) to demonstrate a direct genetic impact on temporal pacing, and (3) to further elucidate the mechanisms controlling foraging initiation. Honey bees selected for differences in stored pollen demonstrate consistent differences in foraging initiation age. Those selected for increased pollen storage (high pollen hoarding strain, HSBs) initiate foraging earlier in life than those selected for decreased pollen storage (low pollen hoarding strain, LSBs). We found that HSBs both initiate and terminate individual pre-foraging tasks earlier than LSBs when housed in a common hive environment. Unselected commercial bees (wild type) generally demonstrated intermediate behavioral timing. There were few differences between genotypes for the proportion of pre-foraging effort dedicated to individual tasks, though total pre-foraging effort differences differed dramatically. This demonstrates that behavioral pacing can be accelerated or slowed, but the pattern of behavior is not fundamentally altered, suggesting a general pattern of temporal behavior in honey bees. This also demonstrates direct genetic control of temporal pacing. Finally, our results suggest that earlier HSB protein (pollen) consumption termination compared to LSBs may contribute to an earlier decline in hemolymph vitellogenin protein titers, which would explain their earlier onset of foraging.

Ovarian control of nectar collection in the honey bee (Apis mellifera).

Honey bees are a model system for the study of division of labor. Worker bees demonstrate a foraging division of labor (DOL) by biasing collection towards carbohydrates (nectar) or protein (pollen). The Reproductive ground-plan hypothesis of Amdam et al. proposes that foraging DOL is regulated by the networks that controlled foraging behavior during the reproductive life cycle of honey bee ancestors. Here we test a proposed mechanism through which the ovary of the facultatively sterile worker impacts foraging bias. The proposed mechanism suggests that the ovary has a regulatory effect on sucrose sensitivity, and sucrose sensitivity impacts nectar loading. We tested this mechanism by measuring worker ovary size (ovariole number), sucrose sensitivity, and sucrose solution load size collected from a rate-controlled artificial feeder. We found a significant interaction between ovariole number and sucrose sensitivity on sucrose solution load size when using low concentration nectar. This supports our proposed mechanism. As nectar and pollen loading are not independent, a mechanism impacting nectar load size would also impact pollen load size.