Impact of the COVID-19 pandemic on breast cancer patient pathways and outcomes in the United Kingdom and the Republic of Ireland - a scoping review.

The COVID-19 pandemic brought unplanned service disruption for breast cancer diagnostic, treatment and support services. This scoping review describes these changes and their impact in the UK and the Republic of Ireland based on studies published between January 2020 and August 2023. Thirty-four of 569 papers were included. Data were extracted and results thematically organized. Findings include fewer new cases; stage shift (fewer early- and more late-stage disease); and changes to healthcare organization, breast screening and treatment. Examples are accepting fewer referrals, applying stricter referral criteria and relying more on virtual consultations and multi-disciplinary meetings. Screening service programs paused during the pandemic before enacting risk-based phased restarts with longer appointment times to accommodate reduced staffing numbers and enhanced infection-control regimes. Treatments shifted from predominantly conventional to hypofractionated radiotherapy, fewer surgical procedures and increased use of bridging endocrine therapy. The long-term impact of such changes are unknown so definitive guidelines for future emergencies are not yet available. Cancer registries, with their large sample sizes and population coverage, are well placed to monitor changes to stage and survival despite difficulties obtaining definitive staging during diagnosis because surgery and pathological assessments are delayed. Multisite longitudinal studies can also provide guidance for future disaster preparedness.

Mastitis and Mammary Abscess Management Audit (MAMMA) in the UK and Ireland.

BACKGROUND: The aim of this multicentre prospective audit was to describe the current practice in the management of mastitis and breast abscesses in the UK and Ireland, with a specific focus on rates of surgical intervention. METHODS: This audit was conducted in two phases from August 2020 to August 2021; a phase 1 practice survey and a phase 2 prospective audit. Primary outcome measurements for phase 2 included patient management pathway characteristics and treatment type (medical/radiological/surgical). RESULTS: A total of 69 hospitals participated in phase 2 (1312 patients). The key findings were a high overall rate of incision and drainage (21.0 per cent) and a lower than anticipated proportion of ultrasound-guided aspiration of breast abscesses (61.0 per cent). Significant variations were observed regarding the rate of incision and drainage (range 0-100 per cent; P < 0.001) and the rate of needle aspiration (range 12.5-100 per cent; P < 0.001) between individual units. Overall, 22.5 per cent of patients were admitted for inpatient treatment, out of whom which 72.9 per cent were commenced on intravenous antibiotics. The odds of undergoing incision and drainage for a breast abscess or being admitted for inpatient treatment were significantly higher if patients presented at the weekend compared with a weekday (P ≤ 0.023). Breast specialists reviewed 40.9 per cent of all patients directly, despite the majority of patients (74.2 per cent) presenting within working hours on weekdays. CONCLUSIONS: Variation in practice exists in the management of mastitis and breast abscesses, with high rates of incision and drainage in certain regions of the UK. There is an urgent need for a national best-practice toolbox to minimize practice variation and standardize patient care.

Mastitis and breast abscess is a painful infection of the breast. It is an extremely common breast problem. One in three women can get this condition at some stage in their life. To treat a breast abscess, the pus inside should be drained out of the body. This can be done either by cutting into the breast using surgery or by inserting a fine needle using an ultrasonography scan (which uses ultrasound). Fine-needle drainage has the benefit that it does not require admission to hospital. Surgery can cause the breast to look misshapen. It is unknown which method is used more often in the UK and Ireland. The aim of this study was to describe how mastitis and breast abscesses are treated in the UK and Ireland. This study involved a survey of practice (phase 1) and collection of data, which are routinely recorded for these patients (phase 2). This study involved 69 hospitals and 1312 patient records. One in five women had an operation for a breast abscess. This was higher than expected. Six in 10 women had a pus drainage using a fine needle. The chance of having an operation depended on the hospital. Women that came to hospital at the weekend were almost twice as likely to have an operation. One in five women were admitted to hospital. The chances of that more than doubled if a woman came to hospital at the weekend. There are differences in treatment of mastitis and breast abscesses across the UK and Ireland. Changes need to be put in place to make access to treatment more equal.

The evolving high bar longswing in elite gymnasts of three age groups.

Chronological age classifies elite male gymnasts into developmental performance classifications: senior (18+ years), junior (14-18 years) and development (8-14 years). Here, we examine the influence of age and experience on the biomechanics of the high bar longswing across classifications. Joint angular kinematics and kinetics were obtained from 30 gymnasts performing three sets each of eight consecutive longswings. Differences between groups and relations between age, experience and key biomechanical variables were correlated. Kinetic variables and range of motion of the hip and knee were highest for development gymnasts. In all age groups, a dominant shoulder kinetic contribution was found, although circle location of the peak joint kinetics occurred earliest for junior gymnasts. Hip work contributed more prominently in development gymnasts. Age and experience were positively correlated to an increase in peak shoulder moments and powers and negatively correlated to peak hip and knee moments. The findings reveal that age and experience combine to influence the functional phase, joint kinematics and relative joint kinetic contribution, particularly with the senior group demonstrating a shoulder dominant technique. Changes in musculoskeletal loading across the age groups suggest that factors such as relative strength and practice may have influenced this joint mode transition of the longswing.

Upper limb biomechanics and dynamics of a core skill on floor exercise in female gymnastics.

This study aimed to increase understanding of the biomechanics and dynamics of the upper limbs during the contact phase of the round-off (RO) performed using three techniques. Twenty female gymnasts performed six successful RO trials in each condition: parallel, T-shape and reverse. Kinetic and kinematic data were collected for each trial. All analyses focused on the contact phase for each hand. Continuous joint profiles examined the dynamics of these tasks as well as the kinetic sequencing. In each case, joint angles, angular velocity, moments and powers at the wrist and elbow joint were reported. Difference between the contact phases of the techniques was examined using a one-way ANOVA SPM. The T-shape technique demonstrated negative power at the wrist during contact; however, the elbow joint compensated with a significantly greater positive power generation during the propulsive phase, suggesting a more effective technique compared to the reduced powers of the reverse and parallel. The order of the peak joint powers during the contact phase, the reverse technique, demonstrated a proximal to distal sequence, in contrast to the distal to proximal for the other techniques. These findings highlight the task-specific coordinative structures during this closed chained action.

Does lateral banking and radius affect well-trained sprinters and team-sports players during bend sprinting?

This study investigated the short-term responses of step characteristics in sprinters and team-sports players under different bend conditions. Eight participants from each group completed 80 m sprints in four conditions: banked and flat, in lanes two and four (L2B, L4B, L2F, L4F). Groups showed similar changes in step velocity (SV) across conditions and limbs. However, sprinters produced significantly shorter ground contact times (GCT) than team sports players in L2B and L4B for both left (0.123 s vs 0.145 s and 0.123 s vs 0.140 s) and right steps (0.115 s vs 0.136 s and 0.120 s vs 0.141 s) (p > 0.001-0.029; ES = 1.15-1.37). Across both groups, SV was generally lower in flat conditions compared to banked (Left: 7.21 m/s vs 6.82 m/s and Right: 7.31 m/s vs 7.09 m/s in lane two), occurring due to reduced step length (SL) rather than step frequency (SF), suggesting that banking improves SV via increased SL. Sprinters produced significantly shorter GCT in banked conditions that led to non-significant increases in SF and SV, highlighting the importance of bend sprinting specific conditioning and training environments representative of indoor competition for sprint athletes.

Identification of a BRCA1-mRNA splicing complex required for efficient DNA repair and maintenance of genomic stability.

Mutations within BRCA1 predispose carriers to a high risk of breast and ovarian cancers. BRCA1 functions to maintain genomic stability through the assembly of multiple protein complexes involved in DNA repair, cell-cycle arrest, and transcriptional regulation. Here, we report the identification of a DNA damage-induced BRCA1 protein complex containing BCLAF1 and other key components of the mRNA-splicing machinery. In response to DNA damage, this complex regulates pre-mRNA splicing of a number of genes involved in DNA damage signaling and repair, thereby promoting the stability of these transcripts/proteins. Further, we show that abrogation of this complex results in sensitivity to DNA damage, defective DNA repair, and genomic instability. Interestingly, mutations in a number of proteins found within this complex have been identified in numerous cancer types. These data suggest that regulation of splicing by the BRCA1-mRNA splicing complex plays an important role in the cellular response to DNA damage.

Task Specific and General Patterns of Joint Motion Variability in Upright- and Hand-Standing Postures.

The preservation of static balance in both upright- and hand-stance is maintained by the projection of center of mass (CM) motion within the region of stability at the respective base of support. This study investigated, from a degrees of freedom (DF) perspective, whether the stability of the CM in both upright- and hand-stances was predicted by the respective dispersion and time-dependent regularity of joint (upright stance-ankle, knee, hip, shoulder, neck; hand stance-wrist, elbow, shoulder, neck) angle and position. Full body three-dimensional (3D) kinematic data were collected on 10 advanced level junior female gymnasts during 30 s floor upright- and hand-stands. For both stances the amount of the dispersion of joint angle and sway motion was higher than that of the CM and center of pressure (CP) with an inverse relation to time-dependent irregularity (SampEn). In upright-standing the variability of neck motion in the anterior-posterior direction was significantly greater than that of most joints consistent with the role of vision in the control of quiet upright posture. The findings support the proposition that there are both task specific and general properties to the global CM control strategy in the balance of upright- and hand-standing induced by the different active skeletal-muscular organization and the degeneracy revealed in the multiple distributional variability patterns of the joint angle and position in 3D.

Effects of biofeedback on whole lower limb joint kinematics and external kinetics.

Biofeedback (BFb) is a useful tool to accelerate the skill development process. Limited research has applied BFb to the whole lower-limb in a complex skill therefore the aim of this research was to assess the effectiveness of a biofeedback intervention targeting whole lower limb kinematics. Thirty-two healthy participants were randomized to a BFb (n = 16) and a Control group (n = 16). Participants visited a motion capture laboratory on three occasions during one week, and returned for retention testing at 4-6 weeks. Following introduction to a novel lunge-touch task, visual BFb on lower limb joint kinematic extension angular velocities (ω) and timing were provided following each lunge. BFb was effective in increasing Hipω (F = 3.746, p = 0.03) and Kneeω (F = 10.241, p = 0.01). Peak Ankleω remained unchanged (F = 1.537, p = 0.23, η2 = 0.05), however Peak Ankleθ (F = 10.915, p < 0.001, η2 = 0.27) and AnkleROM (F = 9.543, p < 0.001, η2 = 0.24) significantly increased. Despite kinematic changes, there were no significant changes in any external kinetics. No significant correlations were found between Hipω, Kneeω or Ankleω and horizontal impulse (ImpulseY: r = 0.20, p = 0.26; r = -0.11, p = 0.24; and r = 0.22, p = 0.28, respectively). Findings demonstrate that BFb can be used to alter multiple kinematic variables in a complex skill, but do not necessarily alter associated kinetic variables not directly targeted by BFb.

Learning the high bar longswing:II. energetics and the emergence of the coordination pattern.

This paper is Part II of a study of the effects of practice on young adult novice gymnasts learning the movement coordination pattern of the longswing. The focus was the early stage of learning a critical component of the longswing, namely: through joint motion to inject mechanical energy into the upswing segment effectively to complete the longswing circle. Twenty-five novice male gymnasts received expert instruction while practicing two sessions a week for 3 weeks between a pre- and a post-practice assessment test trial. Seven novices completed a full circle by the end of Test 4. Completion of the longswing was positively related to the angular velocity generated in the gravity driven free fall of the initial segment and the greater rate of energy input in the upward segment. A successful performance in terms of the emergent movement pattern requires coordination of the onset, rate and level of energy input to counterbalance the negative influence of gravity on the second half upwards segment. The development of the complete longswing through the emergence of the collective variable dynamics (Paper 1) and biomechanical energetics of the gymnast (Paper 2) informs coaches, scientists and clinicians regarding task decomposition and learning the longswing.

Learning the High Bar Longswing:I. Task Dynamics and Emergence of the Coordination Pattern.

We studied novice gymnasts (N = 25) learning to form the longswing movement coordination pattern. The focus was the emerging behavioural organisation of centre of mass (CM) dynamics and the relative phase of the bar-CM angular motion. Seven novices learned a complete longswing by the end of the study, 8 novices showed no improvement in proportion of circle completed, and the remainder produced modest but persistent increments of final swing height without achieving a full circle. The radial angular velocity generated in the free fall phase and the circle location of bar-CM relative phase progressively and predominantly predicted circle completion. Bar-CM relative phase produced a consistent qualitative relation within- and between-subjects characteristic of a collective variable with the bar leading the CM on the initial downward antiphase segment and the CM leading on the upward antiphase segment. The ratio of these phases was related by the last practice session to degree of circle completion. The findings showed strong individual differences in the effect of practice on the early steps of learning the movement coordination where the progressive emergence of the longswing circle is driven by exploiting the positive- and minimising the negative-influence of gravity on the bar-CM coordination dynamics (candidate collective variable).

A biomechanical approach to evaluate overload and specificity characteristics within physical preparation exercises.

An essential component of any physical preparation programme is the selection of training exercises to facilitate desired performance outcomes, with practitioners balancing the principles of sports training to inform exercise selection. This study aimed to advance biomechanical understanding of the principles of overload and specificity within exercise selection, utilising novel joint kinetic and intra-limb joint coordination analyses. Three-dimensional kinematic and kinetic data were obtained from six male sprinters (100 m PB, 10.64-11.00) performing block starts (competitive motor task) and seven training exercises that encompassed traditionally viewed general and more specific exercises. Results highlighted the challenging nature of exercise selection, with all exercises demonstrating capacity to overload relevant joint kinetic features of the block start. In addition, all exercises were able to promote the emergence of proximal and in-phase extension joint coordination patterns linked with block start execution, although traditionally viewed non-specific exercises elicited greater overall coordination similarity. The current research helps advance biomechanical understanding of overload and specificity within exercise selection, by demonstrating how exercise selection should not solely be based on perceived replication of a competitive motor task. Instead, practitioners must consider how the musculoskeletal determinants of performance are overloaded, in addition to promoting task specific coordination patterns.

The importance of duration and magnitude of force application to sprint performance during the initial acceleration, transition and maximal velocity phases.

Successful sprinting depends on covering a specific distance in the shortest time possible. Although external forces are key to sprinting, less consideration is given to the duration of force application, which influences the impulse generated. This study explored relationships between sprint performance measures and external kinetic and kinematic performance indicators. Data were collected from the initial acceleration, transition and maximal velocity phases of a sprint. Relationships were analysed between sprint performance measures and kinetic and kinematic variables. A commonality regression analysis was used to explore how independent variables contributed to multiple-regression models for the sprint phases. Propulsive forces play a key role in sprint performance during the initial acceleration (r = 0.95 ± 0.03) and transition phases (r = 0.74 ± 0.19), while braking duration plays an important role during the transition phase (r = -0.72 ± 0.20). Contact time, vertical force and peak propulsive forces represented key determinants (r = -0.64 ± 0.31, r = 0.57 ± 0.35 and r = 0.66 ± 0.30, respectively) of maximal velocity phase performance, with peak propulsive force providing the largest unique contribution to the regression model for step velocity. These results clarified the role of force and time variables on sprinting performance.

NUP98 - a novel predictor of response to anthracycline-based chemotherapy in triple negative breast cancer.

BACKGROUND: Triple Negative breast cancer (TNBC) is a poor outcome subgroup of breast cancer defined based on the absence of expression of ERα and PR and HER2 amplification. These hard to treat cancers lack targeted treatment options and are therefore treated with a standard of care (SoC) generic cocktail of DNA damaging chemotherapy, with a wide range of clinical responses. While a subset of TNBC patients respond very well to this treatment, others receive no clinical benefit and die from their disease within a short time period. We currently lack biomarkers to prospectively identify patients likely to relapse and we lack alternate treatment options. METHODS: NUP98 protein expression was investigated in patient samples using two independent tissue microarrays (TMAs), as well as a normal breast TMA. Correlation with pathological response to various chemotherapy regimens was investigated. RESULTS: We have shown that high NUP98 is significantly associated with poor outcome in TNBC patient samples both by gene expression and IHC-based protein analysis. While trends linking NUP98 expression with poorer outcomes were observed in breast cancer overall (and more specifically in the LuminalB Her2- subgroup), significant correlations were observed in TNBC. This appeared to be specific to anthracycline based regimens as the association between NUP98 and response was not observed in patients treated with taxane-based chemotherapy. CONCLUSIONS: We have identified a novel biomarker, NUP98, that can predict response to anthracycline based chemotherapy in TNBC. The ability to prospectively identify patients who are less likely to respond to SoC chemotherapy is a vital step in improving the overall survival of these patients.

Sex differences in elbow and wrist joint loading during the cartwheel and round off with different hand positions performed by young gymnasts.

The aim of the study was to determine if sex differences exist in the key elbow and wrist joint injury risk factors during different cartwheel (CW) and round-off (RO) techniques performed by young male and female artistic gymnasts. Sixteen active young gymnasts (8 males and 8 females) performed 30 successful trials of CW and RO with three different hand positions (parallel (10), T-shape (10) and reverse (10)). Synchronised kinematic and kinetic data were collected for each trial. Two-way repeated measures ANOVA (3 × 2, technique × sex) and effect-sizes (ES) were used for statistical analysis. In conclusion, female gymnasts exhibited greater normalised peak vertical ground reaction forces (VGRF), elbow and wrist compression forces and elbow internal adduction moments during CW and RO skills compared with male gymnasts. In both sexes, the parallel and reverse techniques increased peak VGRF, elbow and wrist compression forces and the elbow internal adduction moment. Increased elbow flexion resulted in decreased peak VGRF, elbow compression forces and elbow internal adduction moment. Injury risk factors including elbow extension and internal adduction moment with axial compression force suggest that a CW and RO in reverse and parallel techniques can be hazardous especially for young female gymnasts.

Integrated tumor identification and automated scoring minimizes pathologist involvement and provides new insights to key biomarkers in breast cancer.

Digital image analysis (DIA) is becoming central to the quantitative evaluation of tissue biomarkers for discovery, diagnosis and therapeutic selection for the delivery of precision medicine. In this study, automated DIA using a new purpose-built software platform (QuPath) is applied to a cohort of 293 breast cancer patients to score five biomarkers in tissue microarrays (TMAs): ER, PR, HER2, Ki67 and p53. This software is able to measure IHC expression following fully automated tumor recognition in the same immunohistochemical (IHC)-stained tissue section, as part of a rapid workflow to ensure objectivity and accelerate biomarker analysis. The digital scores produced by QuPath were compared with manual scores by a pathologist and shown to have a good level of concordance in all cases (Cohen's κ>0.6), and almost perfect agreement for the clinically relevant biomarkers ER, PR and HER2 (κ>0.86). To assess prognostic value, cutoff thresholds could be applied to both manual and automated scores using the QuPath software, and survival analysis performed for 5-year overall survival. DIA was shown to be capable of replicating the statistically significant stratification of patients achieved using manual scoring across all biomarkers (P<0.01, log-rank test). Furthermore, the image analysis scores were shown to consistently lead to statistical significance across a wide range of potential cutoff thresholds, indicating the robustness of the method, and identify sub-populations of cases exhibiting different expression patterns within the p53 and Ki67 data sets that warrant further investigation. These findings have demonstrated QuPath's suitability for fast, reproducible, high-throughput TMA analysis across a range of important biomarkers. This was achieved using our tumor recognition algorithms for IHC-stained sections, trained interactively without the need for any additional tumor recognition markers, for example, cytokeratin, to obtain greater insight into the relationship between biomarker expression and clinical outcome applicable to a range of cancer types.

Patterns of locomotor regulation during the pole vault approach phase.

A successful approach phase is key to achieving high performances in the pole vault. The aim of this study was to explore the nature of locomotor control patterns during the pole vault approach phase. Fourteen well-trained athletes performed ten jumps which were recorded using 2D video sampling at 200 Hz and analysed. Key kinematics were reconstructed from camera data using a modified 2D-DLT. Patterns of regulation were determined from the standard deviation of footfall locations during the approach phase. These patterns were found to be highly individual but structural differences between those who did and those who did not regulate were identified. Regulation of locomotion was associated with an ability to produce functionally adaptable movement patterns and the consistent achievement of desired performance outcomes. Coaches should include training exercises that require intentional use of regulation to aid athletes in achieving the flexibility to adapt to changing constraints during the approach phase. Athletes should be considered on an individual basis in order to effectively, efficiently and safely improve performance.

Joint kinetic determinants of starting block performance in athletic sprinting.

The aim of this study was to explore the relationships between lower limb joint kinetics, external force production and starting block performance (normalised average horizontal power, NAHP). Seventeen male sprinters (100 m PB, 10.67 ± 0.32 s) performed maximal block starts from instrumented starting blocks (1000 Hz) whilst 3D kinematics (250 Hz) were also recorded during the block phase. Ankle, knee and hip resultant joint moment and power were calculated at the rear and front leg using inverse dynamics. Average horizontal force applied to the front (r = 0.46) and rear (r = 0.44) block explained 86% of the variance in NAHP. At the joint level, many "very likely" to "almost certain" relationships (r = 0.57 to 0.83) were found between joint kinetic data and the magnitude of horizontal force applied to each block although stepwise multiple regression revealed that 55% of the variance in NAHP was accounted for by rear ankle moment, front hip moment and front knee power. The current study provides novel insight into starting block performance and the relationships between lower limb joint kinetic and external kinetic data that can help inform physical and technical training practices for this skill.