Compliant Intramedullary Stems for Joint Reconstruction.

The longevity of current joint replacements is limited by aseptic loosening, which is the primary cause of non-infectious failure for hip, knee, and ankle arthroplasty. Aseptic loosening is typically caused either by osteolysis from particulate wear, or by high shear stresses at the bone-implant interface from over-constraint. Our objective was to demonstrate feasibility of a compliant intramedullary stem that eliminates over-constraint without generating particulate wear. The compliant stem is built around a compliant mechanism that permits rotation about a single axis. We first established several models to understand the relationship between mechanism geometry and implant performance under a given angular displacement and compressive load. We then used a neural network to identify a design space of geometries that would support an expected 100-year fatigue life inside the body. We additively manufactured one representative mechanism for each of three anatomic locations, and evaluated these prototypes on a KR-210 robot. The neural network predicts maximum stress and torsional stiffness with 2.69% and 4.08% error respectively, relative to finite element analysis data. We identified feasible design spaces for all three of the anatomic locations. Simulated peak stresses for the three stem prototypes were below the fatigue limit. Benchtop performance of all three prototypes was within design specifications. Our results demonstrate the feasibility of designing patient- and joint-specific compliant stems that address the root causes of aseptic loosening. Guided by these results, we expect the use of compliant intramedullary stems in joint reconstruction technology to increase implant lifetime.

N,N-Alkylation Clarifies the Role of N- and O-Protonated Intermediates in Cyclen-Based 64Cu Radiopharmaceuticals.

Radioisotopes of Cu, such as 64Cu and 67Cu, are alluring targets for imaging (e.g., positron emission tomography, PET) and radiotherapeutic applications. Cyclen-based macrocyclic polyaminocarboxylates are one of the most frequently examined bifunctional chelators in vitro and in vivo, including the FDA-approved 64Cu radiopharmaceutical, Cu(DOTATATE) (Detectnet); however, connections between the structure of plausible reactive intermediates and their stability under physiologically relevant conditions remain to be established. In this study, we share the synthesis of a cyclen-based, N,N-alkylated spirocyclic chelate, H2DO3AC4H8, which serves as a model for N-protonation. Our combined experimental (in vitro and in vivo) and computational studies unravel complex pH-dependent speciation and enable side-by-side comparison of N- and O-protonated species of relevant 64Cu radiopharmaceuticals. Our studies suggest that N-protonated species are not inherently unstable species under physiological conditions and demonstrate the potential of N,N-alkylation as a tool for the rational design of future radiopharmaceuticals.

Racial Disparities in Rates of Revision and use of Modern Features in Total Knee Arthroplasty, a National Registry Study.

BACKGROUND: The purpose of our study was to investigate the association of race and ethnicity with rates of modern implant use and postoperative outcomes in total knee arthroplasty (TKA) using the American Academy of Orthopaedic Surgeons American Joint Replacement Registry. METHODS: Adult TKAs from 2012 to 2020 were queried from the American Joint Replacement Registry. A total of 1,121,457 patients were available for analysis for surgical features and 1,068,210 patients for analysis of outcomes. Mixed-effects multivariable logistic regression models were used to examine the association of race with each individual surgical feature (unicompartmental knee arthroplasty (UKA) and robotic-assisted TKA (RA-TKA)) and 30- and 90-day readmission. A proportional subdistribution hazard model was used to model the risk of revision TKA. RESULTS: On multivariate analyses, compared to White patients, Black (odds ratio (OR): 0.52 P < .0001), Hispanic (OR 0.75 P < .001), and Native American (OR: 0.69 P = .0011) patients had lower rates of UKA, while only Black patients had lower rates of RA-TKA (OR = 0.76 P < .001). White (hazard ratio (HR) = 0.8, P < .001), Asian (HR = 0.51, P < .001), and Hispanic-White (HR = 0.73, P = .001) patients had a lower risk of revision TKA than Black patients. Asian patients had a lower revision risk than White (HR = 0.64, P < .001) and Hispanic-White (HR = 0.69, P = .011) patients. No significant differences existed between groups for 30- or 90-day readmissions. CONCLUSION: Black, Hispanic, and Native American patients had lower rates of UKA compared to White patients, while Black patients had lower rates of RA-TKA compared to White, Asian, and Hispanic patients. Black patients also had higher rates of revision TKA than other races.

Lower Rates of Ceramic Femoral Head Use in Non-White Patients in the United States, a National Registry Study.

BACKGROUND: The purpose of our study was to investigate the association of race and ethnicity with the use of the newest technology and postoperative outcomes in total hip arthroplasty (THA) using the American Academy of Orthopaedic Surgeons (AAOS) American Joint Replacement Registry (AJRR). METHODS: Adult THA procedures were queried from the AJRR from 2012 to 2020. A mixed-effects multivariate regression model was used to evaluate the association of race and ethnicity with the use of the newest technology (ceramic femoral head, dual-mobility implant, and robotic assist) at 30-day, and 90-day readmission. A proportional subdistribution hazard model was used to model a risk of revision THA. RESULTS: There were 85,188 THAs with complete data for an analysis of outcomes and 103,218 for an analysis of ceramic head usage. The median length of follow-up was 37.9 months (interquartile range [IQR] 21.6 to 56.3 months). In multivariate models, compared to White non-Hispanic patients, Black (odds ratio [OR] 0.79, 95% confidence interval [CI] 0.69-0.92, P < .001), Hispanic (OR 0.76, CI 0.59-0.99, P = .037), Asian (OR 0.74, CI 0.55-1.00, P = .045), and Native American (OR 0.52, CI 0.30-0.87, P = .004) patients all had significantly lower rates of ceramic head use in THA. Compared to White non-Hispanic patients, Asian (hazard ratio [HR] 0.39, CI 0.18-0.86, P = .008) and Hispanic (HR 0.43, CI 0.19-0.98, P = .043) patients had significantly lower rates of revision. No differences in 30-day or 90-day readmission rates were seen. CONCLUSION: Black, Hispanic, Native American, and Asian patients had lower rates of ceramic head use in THA when compared to White patients. These differences did not translate into worse clinical outcomes on a short-term follow-up. In fact, Asian patients had lower revision rates compared to non-Hispanic White patients. Additional study is necessary to evaluate the long-term consequence of lower ceramic head use in non-White patients in the United States.

N-Oxides amplify catalyst reactivity and isoselectivity in the ring-opening polymerization of rac-ß-butyrolactone.

N-Oxides can amplify the performance of a lanthanum aminobisphenolate catalyst in the ring-opening polymerization (ROP) of rac-ß-butyrolactone (rac-BBL) to unprecedented levels (TOF/Pm; At RT: 1900 h-1/0.73, At -30 °C: 200 h-1/0.82). Experiments and computations establish donor electronics control catalyst activity, while donor sterics control catalyst deactivation.

Lessons learned from the Global Polio Eradication Initiative: A roadmap for the international COVID-19 vaccination campaign.

The COVID-19 vaccine is lauded by many as one of the greatest accomplishments in modern medicine, with the potential to definitively contain the deadliest pandemic of the last century. With the vaccine rollout now underway in the developing world, a robust, methodical, and swift global distribution effort is required to ensure that it will be done in an equitable manner. Taking into account the vast geographic, socioeconomic, cultural, and political diversity of countries around the world, global vaccination efforts have historically required multifaceted, time consuming, and labor-intensive approaches to be effective. However, with over 33 years of experience from the Global Polio Eradication Initiative - an international health initiative aimed at eradicating poliomyelitis - the COVID-19 vaccination campaign does not have to be approached blindly. Using lessons learned from the Global Polio Eradication Initiative, this paper aims to identify the supply- and demand-side barriers to the success of the international COVID-19 vaccination effort, and ways each can be overcome. Most notably, health systems shortcomings, political and cultural messaging, and civil unrest and violent conflict serve as daunting obstacles to the success of the COVID-19 vaccination campaign. The Global Polio Eradication Initiative has been able to overcome many of these same obstacles with innovative strategies such as context-specific microplanning, robust health surveillance systems, and community-centered education and advocacy programs. Ultimately, while the Global Polio Eradication Initiative is still fighting the battle of polio eradication, it has provided a roadmap for the COVID-19 vaccination campaign to be executed in a more swift and equitable manner.

Radiographic and clinical outcomes of second generation Trabecular Metal™ glenoid components in total shoulder arthroplasty.

BACKGROUND: Total shoulder arthroplasty with second generation porous tantalum glenoid implants (Trabecular Metal™) has shown good short-term outcomes, but mid-term outcomes are unknown. This study describes the clinical, radiographic, and patient-rated mid-term outcomes of total shoulder arthroplasty utilizing cemented Trabecular Metal™ glenoid components. METHODS: Patients who underwent anatomic total shoulder arthroplasty with cemented Trabecular Metal™ glenoid components for primary osteoarthritis were identified for minimum five-year follow-up. The primary outcome measure was implant survival; secondary outcome measures included patient-rated outcome scores, shoulder range of motion findings, and radiographic analysis. RESULTS: Twenty-seven patients were enrolled in the study. Twenty-one patients had full radiographic follow-up. Mean follow-up was 6.6 years. There was 100% implant survival. Shoulder range of motion significantly improved and the mean American Shoulder and Elbow Society score was 89.8. There was presence of metal debris radiographically in 24% of patients. Twenty-nine percent of patients had evidence of radiolucency. Fourteen percent of patients had moderate superior subluxation. CONCLUSION: Total shoulder arthroplasty with second generation cemented Trabecular Metal™ glenoid components yielded good outcomes at mean 6.6-year follow-up. Metal debris incidence and clinical outcomes were similar to short-term findings. The presence of metal debris did not significantly affect clinical outcomes. Continued observation of these patients will elucidate longer-term implant survival.

Thiolate-Thione Redox-Active Ligand with a Six-Membered Chelate Ring via Template Condensation and Its Pt(II) Complexes.

A new template condensation reaction has been discovered in a mixture of Pt(II), thiobenzamide, and base. Four complexes of the general form [Pt(ctaPhR)2], R = CH3 (1a), H (1b), F (1c), Cl (1d), cta = condensed thioamide, have been prepared under similar conditions and thoroughly characterized by 1H NMR and UV-vis-NIR spectroscopy, (spectro)electrochemistry, elemental analysis, and single-crystal X-ray diffraction. The ligand is redox active and can be reduced from the initial monoanion to a dianionic and then trianionic state. Chemical reduction of 1a with [Cp2Co] yielded [Cp2Co]2[Pt(ctaPhCH3)2], [Cp2Co]2[1a], which has been similarly characterized with the addition of EPR spectroscopy and SQUID magnetization. The singly reduced form containing [1a]1-, (nBu4N)[Pt(ctaPhCH3)2], has been generated in situ and characterized by UV-vis and EPR spectroscopies. DFT studies of 1b, [1b]1-, and [1b]2- confirm the location of additional electrons in exclusively ligand-based orbitals. A detailed analysis of this redox-active ligand, with emphasis on the characteristics that favor noninnocent behavior in six-membered chelate rings, is included.

Chondral Damage After Arthroscopic Repair Techniques for Acute Bony Bankart Lesions: A Biomechanical Study.

BACKGROUND: Bony Bankart lesions can be encountered during treatment of shoulder instability. Current arthroscopic bony Bankart repair techniques involve intra-articular suture placement, but the effect of these repair techniques on the integrity of the humeral head articular surface warrants further investigation. PURPOSE: To quantify the degree of humeral head articular cartilage damage secondary to current arthroscopic bony Bankart repair techniques in a cadaveric model. STUDY DESIGN: Controlled laboratory study. METHODS: Testing was performed in 13 matched pairs of cadaveric glenoids with simulated bony Bankart fractures, with a defect width of 25% of the glenoid diameter. Half of the fractures were repaired with a double-row technique, while the contralateral glenoids were repaired with a single-row technique. Samples were subjected to 20,000 cycles of internal-external rotation across a 90° arc at 2 Hz after a compressive load of 750 N, or 90% body weight (whichever was less) was applied to simulate wear. Cartilage defects on the humeral head were quantified through a custom MATLAB script. Mean cartilage cutout differences were analyzed by the Wilcoxon rank-sum test. RESULTS: Both single- and double-row repairs showed macroscopic damage. The histomorphometric analysis demonstrated that the double-row technique resulted in a significantly (P = .036) more chondral damage (mean, 57,489.1 µm2; SD, 61,262.2 µm2) than the single-row repair (mean, 28,763.5 µm2; SD, 24,4990.2 µm2). CONCLUSION: Both single-row and double-row arthroscopic bony Bankart fixation techniques resulted in damage to the humeral head articular cartilage in the concavity-compression model utilized in this study. The double-row fixation technique resulted in a significantly increased cutout to the humeral head cartilage after simulated wear in this cadaveric model. CLINICAL RELEVANCE: This study provides data demonstrating that placement of intra-articular suture during arthroscopic bony Bankart repair techniques may harm the humeral head cartilage. While the double-row repair of bony Bankart lesions is more stable, it results in increased cartilage damage. These findings suggest that alternative, cartilage-sparing arthroscopic techniques for bony Bankart repair should be investigated.

Utilization trends and outcomes of computer-assisted navigation in spine fusion in the United States.

BACKGROUND CONTEXT: Computer-assisted navigation (CAN) has emerged in spine surgery as an approach to improve patient outcomes. While there is substantial evidence demonstrating improved pedicle screw accuracy in CAN as compared to conventional spinal fusion (CONV), there is limited data regarding clinical outcomes and utilization trends in the United States. PURPOSE: The purpose of this study was to determine the utilization rates of CAN in the United States, identify patient and hospital trends associated with both techniques, and to compare their results. STUDY DESIGN: Retrospective review of national database. PATIENT SAMPLE: Nationwide Inpatient Sample (NIS), United States national database. OUTCOME MEASURES: CAN utilization, mortality, medical complications, neurologic complications, discharge destination, length of hospital stay, cost of hospital stay. METHODS: The NIS database was queried to identify patients undergoing spinal fusion with CAN or CONV. CAN and CONV utilization were tracked by year and anatomic location (cervical, thoracic, lumbar/lumbosacral). Patient demographics, hospital characteristics, index length of stay (LOS), and cost of stay (COS) were compared between the cohorts. After multivariate adjustment, index hospitalization clinical outcomes were compared. RESULTS: A total of 4,275,413 patients underwent spinal fusion surgery during the study period (2004 to 2014). CONV was performed in 98.4% (4,208,068) of cases and CAN was performed in 1.6% (67,345) of cases. The utilization rate of CAN increased from 0.04% in 2004 to 3.3% in 2014. Overall, CAN was performed most commonly in the lumbar/lumbosacral region (70.4%) compared to the cervical (20.4%) or thoracic (9.2%) regions. When normalized to region-specific rates of fusion with any technique, the proportional utilization of CAN was highest in the thoracic spine (2.7%), followed by the lumbar/lumbosacral (2.2%) and cervical (0.9%) regions. CAN utilization was positively correlated with patient factors including increasing age and number of medical comorbidities. Multivariate adjusted clinical outcomes demonstrated that compared to CONV, CAN was associated with a statistically significant decreased risk of mortality (0.28% vs 0.31%, OR=0.67, 95% CI: 0.46-0.97, p=.035) and increased risk of blood transfusions (9.1% vs 6.7%, OR=1.19, 95% CI: 1.02-1.39, p=.032). However, there was no difference in risk of neurologic complications. CAN patients had an increased average LOS (4.44 days vs. 3.97 days, p<.0001) and average COS ($34,669.49 vs $26,784.62, p<.0001) compared to CONV patients. CONCLUSIONS: CAN utilization increased in the United States from 2004-2014. Use of CAN was proportionately higher in the thoracic and lumbar/lumbosacral regions and in older patients with more comorbidities. Given the continued trend towards increased CAN utilization, large-scale studies are needed to determine the impact of this technology on long-term clinical outcomes.

A Biomechanical, Cadaveric Evaluation of Single- Versus Double-Row Repair Techniques on Stability of Bony Bankart Lesions.

BACKGROUND: Previous studies comparing stability between single- and double-row arthroscopic bony Bankart repair techniques focused only on the measurements of tensile forces on the bony fragment without re-creating a more physiologic testing environment. PURPOSE: To compare dynamic stability and displacement between single- and double-row arthroscopic repair techniques for acute bony Bankart lesions in a concavity-compression cadaveric model simulating physiologic conditions. STUDY DESIGN: Controlled laboratory study. METHODS: Testing was performed on 13 matched pairs of cadaveric glenoids with simulated bony Bankart fractures with a defect width of 25% of the inferior glenoid diameter. Half of the fractures were repaired with a double-row technique, and the contralateral glenoids were repaired with a single-row technique. To determine dynamic biomechanical stability and ultimate step-off of the repairs, a 150-N load and 2000 cycles of internal-external rotation at 1 Hz were applied to specimens to simulate early rehabilitation. Toggle was quantified throughout cycling with a coordinate measuring machine. Three-dimensional spatial measurements were calculated. After cyclic loading, the fracture displacement was measured. RESULTS: The bony Bankart fragment-glenoid initial step-off was found to be significantly greater (P < .001) for the single-row technique (mean, 896 µm; SD, 282 µm) compared with the double-row technique (mean, 436 µm; SD, 313 µm). The motion toggle was found to be significantly greater (P = .017) for the single-row technique (mean, 994 µm; SD, 711 µm) compared with the double-row technique (mean, 408 µm; SD, 384 µm). The ultimate interface displacement was found to be significantly greater (P = .029) for the single-row technique (mean, 1265 µm; SD, 606 µm) compared with the double-row technique (mean, 795 µm; SD, 398 µm). CONCLUSION: Using a concavity-compression glenohumeral cadaveric model, we found that the double-row arthroscopic fixation technique for bony Bankart repair resulted in superior stability and decreased displacement during simulated rehabilitation when compared with the single-row repair technique. CLINICAL RELEVANCE: The findings from this study may help guide surgical decision-making by demonstrating superior biomechanical properties (improved initial step-off, motion toggle, and interface displacement) of the double-row bony Bankart repair technique when compared with single-row fixation. The double-row repair construct demonstrated increased stability of the bony Bankart fragment, which may improve bony Bankart healing.

Cemented versus uncemented fixation of second-generation Trabecular Metal glenoid components: minimum 5-year outcomes.

BACKGROUND: Total shoulder arthroplasty (TSA) with second-generation Trabecular Metal™ implants (Zimmer, Warsaw, IN, USA) has shown good short-term outcomes. Differences in outcomes between cemented and uncemented fixation are unknown. This study compared the clinical, radiographic, and patient-rated outcomes of TSA with cemented vs. uncemented TM glenoids at minimum 5-year follow-up. METHODS: Patients who underwent anatomic TSA with second-generation TM glenoid components for primary osteoarthritis were identified for minimum 5-year follow-up. The patients were divided into 2 groups: cemented and uncemented glenoid fixation. Outcome measures included implant survival, patient-rated outcome scores (Patient-Reported Outcomes Measurement Information System [PROMIS] and American Shoulder and Elbow Surgeons scores), shoulder range of motion, and radiographic analysis. Findings were compared between groups. RESULTS: The study included 55 shoulders: 27 in the cemented group (21 with full radiographic follow-up) and 28 in the uncemented group (22 with full radiographic follow-up). Both groups had similar follow-up times (6.6 years in cemented group vs. 6.7 years in uncemented group, P = .60). Moreover, the groups did not differ significantly in sex composition, age at the time of surgery, or preoperative Walch glenoid grade distribution. No patients required revision surgery. The 2 groups had similar preoperative range of motion, but patients in the uncemented group had greater follow-up forward flexion (P = .03), external rotation (P < .01), and lateral elevation (P = .03) than did patients in the cemented group. PROMIS scores were not significantly different between groups. American Shoulder and Elbow Surgeons scores were similar (89.8 in cemented group vs. 94.1 in uncemented group, P = .21). Mid-term radiographs showed a metal debris rate of 24% in the cemented group and 27% in the uncemented group. Although these values were not significantly different (P = .90), the frequency of mild metal debris (grade 1-2), when present, was greater in the uncemented group (grade 2 in 6 shoulders) than in the cemented group (grade 1 in 4 and grade 2 in 1, P = .02). There was a greater presence of mild (grade 1) radiolucent lines in the uncemented group (64%) than in the cemented group (29%, P < .01). No glenoid had evidence of loosening (defined by a change in position or radiolucent lines > 2 mm). The presence of metal debris and radiolucent lines did not have a significant effect on clinical outcomes. CONCLUSION: At minimum 5-year follow-up, TSA patients with TM glenoids demonstrated excellent clinical and patient-reported outcomes with a 100% implant survival rate, regardless of cemented vs. uncemented fixation. However, the uncemented group showed a significantly higher rate of radiolucent lines and a higher frequency of mild metal debris. These radiographic findings did not affect the clinical outcomes, and their implications for long-term outcomes and prosthesis survival is unknown.

Is Less More? Influence of the Coordination Geometry of Copper(II) Picolinate Chelate Complexes on Metabolic Stability.

A growing number of copper(II) complexes have been identified as suitable candidates for biomedical applications. Here, we show that the biocompatibility and stability of copper(II) complexes can be tuned by directed ligand design and complex geometry. We demonstrate that azamacrocycle-based chelators that envelope copper(II) in a five-coordinate, distorted trigonal-bipyramidal structure are more chemically inert to redox-mediated structural changes than their six-coordinate, Jahn-Teller-distorted counterparts, as evidenced by electrochemical, crystallographic, electron paramagnetic resonance, and density functional theory studies. We further validated our hypothesis of enhanced inertness in vitro and in vivo by employing Cu-64 radiolabeling of bifunctional analogues appended to a prostate-specific membrane antigen targeting dipeptide. The corresponding Cu-64 complexes were tested for stability in vitro and in vivo, with the five-coordinate system demonstrating the greatest metabolic stability among the studied picolinate complex series.

Community transmission of type 2 poliovirus after cessation of trivalent oral polio vaccine in Bangladesh: an open-label cluster-randomised trial and modelling study.

BACKGROUND: Trivalent oral polio vaccine (tOPV) was replaced worldwide from April, 2016, by bivalent types 1 and 3 oral polio vaccine (bOPV) and one dose of inactivated polio vaccine (IPV) where available. The risk of transmission of type 2 poliovirus or Sabin 2 virus on re-introduction or resurgence of type 2 poliovirus after this switch is not understood completely. We aimed to assess the risk of Sabin 2 transmission after a polio vaccination campaign with a monovalent type 2 oral polio vaccine (mOPV2). METHODS: We did an open-label cluster-randomised trial in villages in the Matlab region of Bangladesh. We randomly allocated villages (clusters) to either: tOPV at age 6 weeks, 10 weeks, and 14 weeks; or bOPV at age 6 weeks, 10 weeks, and 14 weeks and either one dose of IPV at age 14 weeks or two doses of IPV at age 14 weeks and 18 weeks. After completion of enrolment, we implemented an mOPV2 vaccination campaign that targeted 40% of children younger than 5 years, regardless of enrolment status. The primary outcome was Sabin 2 incidence in the 10 weeks after the campaign in per-protocol infants who did not receive mOPV2, as assessed by faecal shedding of Sabin 2 by reverse transcriptase quantitative PCR (RT-qPCR). The effect of previous immunity on incidence was also investigated with a dynamical model of poliovirus transmission to observe prevalence and incidence of Sabin 2 virus. This trial is registered at ClinicalTrials.gov, number NCT02477046. FINDINGS: Between April 30, 2015, and Jan 14, 2016, individuals from 67 villages were enrolled to the study. 22 villages (300 infants) were randomly assigned tOPV, 23 villages (310 infants) were allocated bOPV and one dose of IPV, and 22 villages (329 infants) were assigned bOPV and two doses of IPV. Faecal shedding of Sabin 2 in infants who did not receive the mOPV2 challenge did not differ between children immunised with bOPV and one or two doses of IPV and those who received tOPV (15 of 252 [6%] vs six of 122 [4%]; odds ratio [OR] 1·29, 95% CI 0·45-3·72; p=0·310). However, faecal shedding of Sabin 2 in household contacts was increased significantly with bOPV and one or two doses of IPV compared with tOPV (17 of 751 [2%] vs three of 353 [1%]; OR 3·60, 95% CI 0·82-15·9; p=0·045). Dynamical modelling of within-household incidence showed that immunity in household contacts limited transmission. INTERPRETATION: In this study, simulating 1 year of tOPV cessation, Sabin 2 transmission was higher in household contacts of mOPV2 recipients in villages receiving bOPV and either one or two doses of IPV, but transmission was not increased in the community as a whole as shown by the non-significant difference in incidence among infants. Dynamical modelling indicates that transmission risk will be higher with more time since cessation. FUNDING: Bill & Melinda Gates Foundation.

Analysis of vaccination campaign effectiveness and population immunity to support and sustain polio elimination in Nigeria.

BACKGROUND: The world is closer than ever to a polio-free Africa. In this end-stage, it is important to ensure high levels of population immunity to prevent polio outbreaks. Here, we introduce a new method of assessing vaccination campaign effectiveness and estimating immunity at the district-level. We demonstrate how this approach can be used to plan the vaccination campaigns prospectively to better manage population immunity in Northern Nigeria. METHODS: Using Nigerian acute flaccid paralysis surveillance data from 2004-2014, we developed a Bayesian hierarchical model of campaign effectiveness and compared it to lot-quality assurance sampling data. We then used reconstructed sero-specific population immunity based on campaign history and compared district estimates of immunity to the occurrence of confirmed poliovirus cases. RESULTS: Estimated campaign effectiveness has improved across northern Nigeria since 2004, with Kano state experiencing an increase of 40 % (95 % CI, 26-54 %) in effectiveness from 2013 to 2014. Immunity to type 1 poliovirus has increased steadily. On the other hand, type 2 immunity was low and variable until the recent use of trivalent oral polio vaccine. We find that immunity estimates are related to the occurrence of both wild and vaccine-derived poliovirus cases and that campaign effectiveness correlates with direct measurements using lot-quality assurance sampling. Future campaign schedules highlight the trade-offs involved with using different vaccine types. CONCLUSIONS: The model in this study provides a novel method for assessing vaccination campaign performance and epidemiologically-relevant estimates of population immunity. Small-area estimates of campaign effectiveness can then be used to evaluate prospective campaign plans. This modeling approach could be applied to other countries as well as other vaccine preventable diseases.

Genetic isolation between coastal and fishery-impacted, offshore bottlenose dolphin (Tursiops spp.) populations.

The identification of species and population boundaries is important in both evolutionary and conservation biology. In recent years, new population genetic and computational methods for estimating population parameters and testing hypotheses in a quantitative manner have emerged. Using a Bayesian framework and a quantitative model-testing approach, we evaluated the species status and genetic connectedness of bottlenose dolphin (Tursiops spp.) populations off remote northwestern Australia, with a focus on pelagic 'offshore' dolphins subject to incidental capture in a trawl fishery. We analysed 71 dolphin samples from three sites beyond the 50 m depth contour (the inshore boundary of the fishery) and up to 170 km offshore, including incidentally caught and free-ranging individuals associating with trawl vessels, and 273 dolphins sampled at 12 coastal sites inshore of the 50 m depth contour and within 10 km of the coast. Results from 19 nuclear microsatellite markers showed significant population structure between dolphins from within the fishery and coastal sites, but also among dolphins from coastal sites, identifying three coastal populations. Moreover, we found no current or historic gene flow into the offshore population in the region of the fishery, indicating a complete lack of recruitment from coastal sites. Mitochondrial DNA corroborated our findings of genetic isolation between dolphins from the offshore population and coastal sites. Most offshore individuals formed a monophyletic clade with common bottlenose dolphins (T. truncatus), while all 273 individuals sampled coastally formed a well-supported clade of Indo-Pacific bottlenose dolphins (T. aduncus). By including a quantitative modelling approach, our study explicitly took evolutionary processes into account for informing the conservation and management of protected species. As such, it may serve as a template for other, similarly inaccessible study populations.

Sexual Dimorphism and Geographic Variation in Dorsal Fin Features of Australian Humpback Dolphins, Sousa sahulensis.

Determining the sex of free-ranging cetaceans can be challenging. Sexual dimorphism among external features may allow inferences on sex, but such patterns may be difficult to detect and are often confounded by age and geographic variation. Dorsal fin images of 107 female and 54 male Australian humpback dolphins, Sousa sahulensis, from Western Australia (WA) and Queensland (QLD) were used to investigate sex, age and geographic differences in colouration, height/length quotient and number of notches. Adult males exhibited more dorsal fin notches (p<0.001) and a significantly greater loss of pigmentation on the upper half of their dorsal fins (p<0.001) than did adult females. These differences likely reflect that males experience a higher frequency and/or intensity of intraspecific aggression than females. In QLD, heavily spotted dorsal fins were more frequent among females than males (p<0.001). Logistic regression analyses revealed that dorsal fin spotting and loss of pigmentation on the upper half of the dorsal fin provided the best model parameters for predicting the sex of sampled adults, with 97% accuracy. This technique offers a rapid, non-invasive method for predicting sex in Australian humpback dolphins, which could potentially be applied to populations throughout their range. In contrast to adults, presumed immature animals showed little or no loss of pigmentation or spotting; however, the rate of development of these features remains unknown. There were pronounced differences between QLD and WA in the intensity of spotting on dorsal fins and the extent of pigmentation loss around the posterior insertion and trailing edge of the dorsal fin. While based on a limited sample size, these geographic differences may have conservation implications in terms of population subdivision and should be investigated further.

Quantifying the impact of expanded age group campaigns for polio eradication.

A priority of the Global Polio Eradication Initiative (GPEI) 2013-2018 strategic plan is to evaluate the potential impact on polio eradication resulting from expanding one or more Supplementary Immunization Activities (SIAs) to children beyond age five-years in polio endemic countries. It has been hypothesized that such expanded age group (EAG) campaigns could accelerate polio eradication by eliminating immunity gaps in older children that may have resulted from past periods of low vaccination coverage. Using an individual-based mathematical model, we quantified the impact of EAG campaigns in terms of probability of elimination, reduction in polio transmission and age stratified immunity levels. The model was specifically calibrated to seroprevalence data from a polio-endemic region: Zaria, Nigeria. We compared the impact of EAG campaigns, which depend only on age, to more targeted interventions which focus on reaching missed populations. We found that EAG campaigns would not significantly improve prospects for polio eradication; the probability of elimination increased by 8% (from 24% at baseline to 32%) when expanding three annual SIAs to 5-14 year old children and by 18% when expanding all six annual SIAs. In contrast, expanding only two of the annual SIAs to target hard-to-reach populations at modest vaccination coverage-representing less than one tenth of additional vaccinations required for the six SIA EAG scenario-increased the probability of elimination by 55%. Implementation of EAG campaigns in polio endemic regions would not improve prospects for eradication. In endemic areas, vaccination campaigns which do not target missed populations will not benefit polio eradication efforts.

Population differentiation and hybridisation of Australian snubfin (Orcaella heinsohni) and Indo-Pacific humpback (Sousa chinensis) dolphins in north-western Australia.

Little is known about the Australian snubfin (Orcaella heinsohni) and Indo-Pacific humpback (Sousa chinensis) dolphins ('snubfin' and 'humpback dolphins', hereafter) of north-western Australia. While both species are listed as 'near threatened' by the IUCN, data deficiencies are impeding rigorous assessment of their conservation status across Australia. Understanding the genetic structure of populations, including levels of gene flow among populations, is important for the assessment of conservation status and the effective management of a species. Using nuclear and mitochondrial DNA markers, we assessed population genetic diversity and differentiation between snubfin dolphins from Cygnet (n = 32) and Roebuck Bays (n = 25), and humpback dolphins from the Dampier Archipelago (n = 19) and the North West Cape (n = 18). All sampling locations were separated by geographic distances >200 km. For each species, we found significant genetic differentiation between sampling locations based on 12 (for snubfin dolphins) and 13 (for humpback dolphins) microsatellite loci (FST = 0.05-0.09; P<0.001) and a 422 bp sequence of the mitochondrial control region (FST = 0.50-0.70; P<0.001). The estimated proportion of migrants in a population ranged from 0.01 (95% CI 0.00-0.06) to 0.13 (0.03-0.24). These are the first estimates of genetic diversity and differentiation for snubfin and humpback dolphins in Western Australia, providing valuable information towards the assessment of their conservation status in this rapidly developing region. Our results suggest that north-western Australian snubfin and humpback dolphins may exist as metapopulations of small, largely isolated population fragments, and should be managed accordingly. Management plans should seek to maintain effective population size and gene flow. Additionally, while interactions of a socio-sexual nature between these two species have been observed previously, here we provide strong evidence for the first documented case of hybridisation between a female snubfin dolphin and a male humpback dolphin.

Predictive spatial risk model of poliovirus to aid prioritization and hasten eradication in Nigeria.

BACKGROUND: One of the challenges facing the Global Polio Eradication Initiative is efficiently directing limited resources, such as specially trained personnel, community outreach activities, and satellite vaccinator tracking, to the most at-risk areas to maximize the impact of interventions. A validated predictive model of wild poliovirus circulation would greatly inform prioritization efforts by accurately forecasting areas at greatest risk, thus enabling the greatest effect of program interventions. METHODS: Using Nigerian acute flaccid paralysis surveillance data from 2004-2013, we developed a spatial hierarchical Poisson hurdle model fitted within a Bayesian framework to study historical polio caseload patterns and forecast future circulation of type 1 and 3 wild poliovirus within districts in Nigeria. A Bayesian temporal smoothing model was applied to address data sparsity underlying estimates of covariates at the district level. RESULTS: We find that calculated vaccine-derived population immunity is significantly negatively associated with the probability and number of wild poliovirus case(s) within a district. Recent case information is significantly positively associated with probability of a case, but not the number of cases. We used lagged indicators and coefficients from the fitted models to forecast reported cases in the subsequent six-month periods. Over the past three years, the average predictive ability is 86 ± 2% and 85 ± 4% for wild poliovirus type 1 and 3, respectively. Interestingly, the predictive accuracy of historical transmission patterns alone is equivalent (86 ± 2% and 84 ± 4% for type 1 and 3, respectively). We calculate uncertainty in risk ranking to inform assessments of changes in rank between time periods. CONCLUSIONS: The model developed in this study successfully predicts districts at risk for future wild poliovirus cases in Nigeria. The highest predicted district risk was 12.8 WPV1 cases in 2006, while the lowest district risk was 0.001 WPV1 cases in 2013. Model results have been used to direct the allocation of many different interventions, including political and religious advocacy visits. This modeling approach could be applied to other vaccine preventable diseases for use in other control and elimination programs.