A synopsis of global frontiers in fertility preservation.

Since 2007, the Oncofertility Consortium Annual Conference has brought together a diverse network of individuals from a wide range of backgrounds and professional levels to disseminate emerging basic and clinical research findings in fertility preservation. This network also developed enduring educational materials to accelerate the pace and quality of field-wide scientific communication. Between 2007 and 2019, the Oncofertility Consortium Annual Conference was held as an in-person event in Chicago, IL. The conference attracted approximately 250 attendees each year representing 20 countries around the world. In 2020, however, the COVID-19 pandemic disrupted this paradigm and precluded an in-person meeting. Nevertheless, there remained an undeniable demand for the oncofertility community to convene. To maintain the momentum of the field, the Oncofertility Consortium hosted a day-long virtual meeting on March 5, 2021, with the theme of "Oncofertility Around the Globe" to highlight the diversity of clinical care and translational research that is ongoing around the world in this discipline. This virtual meeting was hosted using the vFairs ® conference platform and allowed over 700 people to participate, many of whom were first-time conference attendees. The agenda featured concurrent sessions from presenters in six continents which provided attendees a complete overview of the field and furthered our mission to create a global community of oncofertility practice. This paper provides a synopsis of talks delivered at this event and highlights the new advances and frontiers in the fields of oncofertility and fertility preservation around the globe from clinical practice and patient-centered efforts to translational research.

Carbonate chemistry of an in-situ free-ocean CO2 enrichment experiment (antFOCE) in comparison to short term variation in Antarctic coastal waters.

Free-ocean CO2 enrichment (FOCE) experiments have been deployed in marine ecosystems to manipulate carbonate system conditions to those predicted in future oceans. We investigated whether the pH/carbonate chemistry of extremely cold polar waters can be manipulated in an ecologically relevant way, to represent conditions under future atmospheric CO2 levels, in an in-situ FOCE experiment in Antarctica. We examined spatial and temporal variation in local ambient carbonate chemistry at hourly intervals at two sites between December and February and compared these with experimental conditions. We successfully maintained a mean pH offset in acidified benthic chambers of -0.38 (±0.07) from ambient for approximately 8 weeks. Local diel and seasonal fluctuations in ambient pH were duplicated in the FOCE system. Large temporal variability in acidified chambers resulted from system stoppages. The mean pH, Ωarag and fCO2 values in the acidified chambers were 7.688 ± 0.079, 0.62 ± 0.13 and 912 ± 150 µatm, respectively. Variation in ambient pH appeared to be mainly driven by salinity and biological production and ranged from 8.019 to 8.192 with significant spatio-temporal variation. This experiment demonstrates the utility of FOCE systems to create conditions expected in future oceans that represent ecologically relevant variation, even under polar conditions.

Accuracy of preoperative CT T staging of renal cell carcinoma: which features predict advanced stage?

AIMS: To characterise CT findings in renal cell carcinoma (RCC), and establish which features are associated with higher clinical T stage disease, and to evaluate patterns of discrepancy between radiological and pathological staging of RCC. MATERIALS AND METHODS: Preoperative CT studies of 92 patients with 94 pathologically proven RCCs were retrospectively reviewed. CT stage was compared with pathological stage using the American Joint Committee on Cancer (AJCC), 7(th) edition (2010). The presence or absence of tumour necrosis, perinephric fat standing, thickening of Gerota's fascia, collateral vessels were noted, and correlated with pT stage. The sensitivity, specificity, and positive (PPV) and negative predictive values (NPV) for predicting pT stage ≥pT3a were derived separately for different predictors using cross-tabulations. RESULTS: Twenty-four lesions were pathological stage T1a, 21 were T1b, seven were T2a, 25 were T3a, 11 were T3b, four were T3c, and two were T4. There were no stage T2b. Sixty-three (67%) patients had necrosis, 27 (29%) thickening of Gerota's fascia (1 T1a), 25 had collateral vessels (0 T1a), 28 (30%) had fat stranding of <2 mm, 20 (21%) of 2-5mm and one (1%) of >5 mm. For pT stage ≥pT3a, the presence of perinephric fat stranding had a sensitivity, specificity, PPV and NPV of 74%, 65%, 63%, and 76%, respectively. Presence of tumour necrosis had a sensitivity, specificity, PPV, and NPV of 81%, 44%, 54%, and 72%, respectively. Thickening of Gerota's fascia had a sensitivity, specificity, PPV, and NPV of 52%, 90%, 81% and 70%, respectively; and enlarged collateral vessels had a sensitivity, specificity, PPV, and NPV value of 52%, 94%, 88%, and 71% respectively. CONCLUSION: The presence of perinephric stranding and tumour necrosis were not reliable signs for pT stage >T3a. Thickening of Gerota's fascia and the presence of collateral vessels in the peri- or paranephric fat had 90% and 94% specificity, with 82% and 88% PPV, respectively, for the presence of tumour stage for pT stage >T3a. These are considered reliable signs of locally advanced renal cancer.

Predicting women at risk for developing obstetric fistula: a fistula index? An observational study comparison of two cohorts.

OBJECTIVE: To ascertain if a predictor of obstructed labour and obstetric fistula (OF) occurrence could be devised. DESIGN: Observational study of two cohorts. SETTING: Selian Lutheran Mission Hospital, Arusha, Tanzania and Aberdeen Women's Centre, Freetown, Sierra Leone. POPULATION: All women presenting with OF caused by obstructed labour and all women having a normal vaginal delivery (NVD) at both institutions were eligible for the study. METHODS: All women with OF and those delivering normally had their height in centimetres measured and their intertuberous space measured by the number of examiner's knuckles admitted. The dimensions for OF and normal delivery were examined individually and multiplied to gain a 'fistula index'. MAIN OUTCOMES MEASURES: Dimensions and index were compared statistically between OF and NVD women using t tests. Sensitivity, specificity and predictive values from receiver operating characteristic curves were obtained for predicting OF. RESULTS: There were statistical differences between the groups with OF women being significantly shorter, having a smaller intertuberous space and lower fistula index than those undergoing NVD (each P < 0.001). Sensitivity was high for fistula index ≤ 507.5 (94.9%, 95% confidence interval 83.1-98.6%) and for intertuberous space of at least three knuckles (92.3%, 95% CI 79.7-97.3%) alone. CONCLUSIONS: A simple antenatal measurement of intertuberous space could screen those women at higher risk of needing medical intervention to prevent OF.

Optical coherence tomography: a reliable alternative to invasive histological assessment of acute wound healing in human skin?

BACKGROUND: Gold-standard assessment of acute wound healing has traditionally been through histological analysis of biopsied tissue. However, this process is invasive with recognized side-effects. Optical coherence tomography (OCT) is a noninvasive technique generating high-resolution real-time images of cutaneous architecture. OBJECTIVES: To compare OCT with histological assessment of in vivo acute wound healing and ascertain the level of agreement between modalities for measurement of defined cutaneous structures. METHODS: Punch biopsies (5 mm) were harvested from 50 healthy volunteers. Wounds healed by secondary intention until they were re-excised 7, 14, 21 or 28 days later depending on random group allocation. Wounds were assessed weekly for 6 weeks using OCT and compared with histological findings derived from time-matched biopsies. Dimensions of four cutaneous structures were measured using both modalities and the level of agreement was established by Bland-Altman analysis. The mean greyscale value (MGV) of the upper reticular dermis was derived from OCT images at all time points. RESULTS: Both techniques showed anatomical congruity in normal and wounded skin with correlating architectural changes associated with inflammatory, proliferative and remodelling wound healing phases. MGV was significantly increased 6 weeks after wounding (P = 0·001) and may represent a novel measure of wound fibrosis. Despite good association of histomorphometric values with low but consistent bias (range -4·181 to 0·431 µm), Bland-Altman plots demonstrated poor agreement between OCT and histology. CONCLUSIONS: Optical coherence tomography enabled accurate assessment of healing tissue comparable with histological analysis of biopsy specimens. This noninvasive tool is highly suited to wound assessment and may represent a diagnostic alternative to punch biopsies.

Impact of full-field digital mammography on pre-operative diagnosis and surgical treatment of mammographic microcalcification.

Accurate pre-operative diagnosis of impalpable breast lesions correlates closely with the number of surgical procedures required for treatment. Correct diagnosis of mammographic microcalcification (MM) as ductal carcinoma in situ (DCIS) or invasive breast cancer is important because lesions upgraded to malignant diagnosis at surgery require repeat surgical procedures in 44 % of cases. Despite correct pre-operative diagnosis of MM, 26 % require second therapeutic operations to achieve surgical clearance. Theoretically, improved conspicuity of malignant MM using digital mammography could improve diagnostic work-up and improve surgical outcomes for MM. To determine the impact of full-field digital mammography (FFDM) on the diagnostic accuracy and positive predictive value (PPV) of biopsy of MM and surgical management of MM, screening and symptomatic cases with MM (n = 1,479) were reviewed for women imaged between August 2007 and March 2010 using screen-film mammography (SFM) (n = 711), and using FFDM, imaged between April 2010 to March 2012 (n = 768). Demographic information including pre and postoperative diagnosis, and number and types of surgical procedures were recorded. Overall, 302 (128 invasive) and 251 (110 invasive) malignant lesions were diagnosed using SFM and FFDM, respectively. Reduction in PPV of biopsy was observed (SFM 42.5 %; FFDM 32.7 %, p < 0.001). Correct pre-operative diagnosis was achieved at first attempt more often with FFDM (SFM 80.6 %; FFDM 89.5 %, p < 0.001). For lesions with pre-operative diagnosis, B5 more cases achieved surgical clearance with a single therapeutic operation with FFDM (SFM 66.3 %; FFDM 76.7 %, p = 0.017), and more lesions over 2 cm underwent mastectomy as the initial surgical procedure (SFM 47.0 %; FFDM 62.9 %, p = 0.005). Correct pre-operative diagnosis of MM using digital mammography reduced second therapeutic operations but increased mastectomy rate in larger cancers over two centimetres. This will increase concerns about treatment of lesions detected in the screening programme with widespread use of digital mammography.

Isolation of Aspergillus species from the airway of lung transplant recipients is associated with excess mortality.

BACKGROUND: Aspergillus spp. are the leading cause of invasive fungal infection in lung transplant recipients. We investigated the relationship between the isolation of Aspergillus spp. from the respiratory tract of lung transplant recipients and their risk of mortality. METHODS: A retrospective, observational cohort study of all patients who received lung allografts between January 1999 and May 2011 at a single UK centre was performed. The time from transplantation to death was analysed using Cox regression models. Isolation of Aspergillus spp. from the respiratory tract was included as a covariate in the Cox regression model. RESULTS: Two hundred-thirteen patients were included. The median follow-up time was 5 years during which 102 patients (47.9%) died. Aspergillus was isolated from 74 (34.7%) patients. Twenty patients (27%) had Aspergillus isolated in the first 60 days post-transplant. Forty-one patients (55.4%) in the Aspergillus group and 61 patients (43.9%) in the non-Aspergillus group died during follow-up. A hazard ratio of 2.2 (95% CI 1.5-3.3; P < 0.001) for death following a positive Aspergillus sample was observed. CONCLUSION: Isolation of Aspergillus spp. from patients following lung transplantation is associated with a significant increase in mortality. Novel preventative strategies are required to minimise the impact of Aspergillus in lung transplant recipients.

Is thought-action fusion specific to obsessive-compulsive disorder?: a mediating role of negative affect.

Thought-action fusion (TAF) is a cognitive bias presumed to underlie the development of obsessional problems (i.e. obsessive-compulsive disorder; OCD). Previous studies have found that TAF is related to not only OCD, but also to other anxiety disorders. In the present study we compared levels of TAF in OCD patients and in patients with other anxiety disorders, depression, and healthy controls to examine whether TAF is characteristic of individuals with emotional distress in general, as opposed to anxiety disorders per se. We also examined whether negative affect (i.e. anxiety and depression) mediates the relationship between OCD and TAF. Results indicated that OCD patients were characterized by higher scores on likelihood-self and likelihood-other TAF, but that this difference was predominately due to differences in negative affect. These findings support a model in which negative affect mediates the relationship between OCD and TAF.

Early dissemination of foot-and-mouth disease virus through sheep marketing in February 2001.

The results of epidemiological investigations suggest that livestock on up to 79 premises, spread widely throughout the British Isles, may have been exposed to infection by foot-and-mouth disease (FMD) virus by the movement of infected sheep before the first case of the disease was confirmed at an abattoir in Essex on February 20, 2001. A further 36 premises may have been infected by this route before the national livestock movement ban was imposed on February 23.

Thought control strategies in obsessive-compulsive disorder: a replication and extension.

Previous research suggests that individuals with OCD use maladaptive strategies to control their unpleasant thoughts (Behav Res Ther (1977) 35, 775). These include worry and self-punishment strategies. In the present study we replicated and extended the previous findings by comparing thought control strategies used by patients with OCD to strategies used by anxious and non-anxious control participants. We also examined changes in thought control strategies for OCD patients who underwent cognitive-behavioral therapy. Compared to controls, OCD patients reported more frequent use of worry and punishment strategies, and less frequent use of distraction. Following successful treatment, OCD patients evidenced increased use of distraction and decreased use of punishment. Findings are discussed in terms of the cognitive model of OCD.

Speech characteristics of monozygotic twins and a same-sex sibling: an acoustic case study of coarticulation patterns in read speech.

This case study reports on an acoustic investigation of the motor speech characteristics of a set of young adult male monozygotic (MZ) twins and compares them to those of an age- and sex-matched sibling who participated in the study 2 years later to match for demographic factors. Coarticulation patterns were investigated from read samples of consonant-vowel sequences in monosyllabic words containing a variety of consonants and vowels. This was done by examining F(2) vowel onsets and F(2) vowel targets, plotted as F(2) locus equations. Data were processed for between-sibling differences using a number of statistical tests. Results indicated that the MZ twins displayed F(2) parameters and coarticulation patterns which were more similar than those of their age- and sex-matched sibling. The results of this case study therefore suggest that acoustic phonetic parameters used to index coarticulation patterns have the potential to profile some of the similarities and differences in the speech characteristics of genetically related individuals.

Vocal characteristics in pre-adolescent and adolescent children: a longitudinal study.

A number of cross-sectional studies have been reported for the fundamental frequency and formant frequency data in the voices of a group of 20 pre-adolescent children aged between 6 and 10 years (Whiteside, S P, Hodgson, C. Acoustic characteristics in 6-10-year old children's voices: some preliminary findings, Log Phon Vocol 1999; 24: 6-13, Whiteside, SP, Hodgson, C. Some acoustic characteristics in the voices of 6-10-year-old children and adults: a comparative sex and developmental perspective, Log Phon Vocol 2000; 25: 122-132). About 15 of the children who participated in these earlier studies, participated in a follow-up study approximately 42 months later. Their speech data were recorded and analysed acoustically to investigate longitudinal patterns of development in their voices by examining data for fundamental frequency and the first three formant frequencies of a phrase final vowel. Data obtained from this follow-up study (Time 2) were compared with earlier corresponding data (Time 1). The findings of this study indicated that there was evidence for maturation in the voice parameters of all subjects between Time 1 and 2, with changes being observed for the majority of comparisons for parameters, across age and sex. In addition there was also evidence of individual differences in the maturational patterns which were observed. These individual differences highlight the degree of variation which occurs in the developmental changes of voice characteristics.

College-age males' ability to produce the acoustic properties of an aging voice: some suggestions for further exploration.

Manning, et al. recently reported on the ability of college-age males to imitate the voice of an aging male. This commentary briefly discusses how their data could be extended to support their published findings.

Sex-specific fundamental and formant frequency patterns in a cross-sectional study.

An extensive developmental acoustic study of the speech patterns of children and adults was reported by Lee and colleagues [Lee et al., J. Acoust. Soc. Am. 105, 1455-1468 (1999)]. This paper presents a reexamination of selected fundamental frequency and formant frequency data presented in their report for ten monophthongs by investigating sex-specific and developmental patterns using two different approaches. The first of these includes the investigation of age- and sex-specific formant frequency patterns in the monophthongs. The second, the investigation of fundamental frequency and formant frequency data using the critical band rate (bark) scale and a number of acoustic-phonetic dimensions of the monophthongs from an age- and sex-specific perspective. These acoustic-phonetic dimensions include: vowel spaces and distances from speaker centroids; frequency differences between the formant frequencies of males and females; vowel openness/closeness and frontness/backness; the degree of vocal effort; and formant frequency ranges. Both approaches reveal both age- and sex-specific development patterns which also appear to be dependent on whether vowels are peripheral or nonperipheral. The developmental emergence of these sex-specific differences are discussed with reference to anatomical, physiological, sociophonetic, and culturally determined factors. Some directions for further investigation into the age-linked sex differences in speech across the lifespan are also proposed.

Developmental trends in voice onset time: some evidence for sex differences.

This study reports on an investigation into the voice onset time (VOT) patterns of the plosives /p b t d/ in a group of 30 children aged 7 (n = 10), 9 (n = 10) and 11 (n = 10) years. Equal numbers of girls and boys participated in the study. Each child named a series of letter objects to elicit /p b t d/ in a syllable onset position with a fixed vowel context. VOT data were examined for age, sex and plosive differences with the following hypotheses: Firstly, that there would be sex differences in the VOT patterns of preadolescent children. Secondly, that the sex differences in VOT patterns would be linked to age and development, and that these would eventually become marked by the age of 11 years, by which time adult-like VOT values should have been achieved. Finally, that the extent of sex and age differences would be dependent upon the plosive being investigated. Results indicated patterns of decrease with age in the VOT values of /p b/ for the boys, with some evidence of increases in the VOT values of /t/ for the girls. In addition, 'voiced' and 'voiceless' cognates showed a more marked bimodal distribution in the girls' VOT patterns. This bimodal distribution was investigated by examining the degree of difference between the VOT values of voiced and voiceless cognate pairs /p b/ and /t d/, and examining the effects of age, sex and cognate pair. These results indicated that more marked sex differences in the 'voiced'/'voiceless' contrast emerged between the data of the 9- and 11-year-olds, a pattern, which was more marked for the alveolar plosives. These preliminary results confirmed all three hypotheses. The findings are presented and discussed both within a developmental and sociophonetic framework.

Comment on delayed left-ear accuracy in dichotic listening.

Moulden and Persinger recently reported on the emergence of left-ear accuracy during childhood and adolescence. This commentary briefly discusses their findings with reference to previous studies that have reported on dichotic listening paradigms and, in particular, those in which a left-ear focus was used as a behavioral probe sensitive to developmental sex differences.

Some acoustic characteristics in the voices of 6- to 10-year-old children and adults: a comparative sex and developmental perspective.

This study is a follow-up investigation of some of the acoustic characteristics reported for a group of twenty 6-, 8- and 10-year-old children's voices (Whiteside SP, Hodgson C. Log Phon Vocol 1999; 24: 6-13) and compares the data of these children with data from a group of nine adults. The acoustic characteristics for both the children and the adults were examined as a function of age and sex. Fundamental frequency (F0) and the standard deviation (SD) of F0 were investigated for the entire duration of a phrase-final vowel. In addition, the first three formant frequencies of the midpoints for the phrase-final vowel were also investigated, with reference to phonetic context. All acoustic parameters were investigated by examining the age, sex and context-determined differences. Results indicated significant age differences for all acoustic parameters investigated, which were characterized by a general decrease in the frequency values of parameters with increasing age. In addition, significant sex differences were found for all parameters, with the females generally having higher formant frequency values than their male peers across all ages. Significant phonetic context differences were only found for the second formant frequency, with formant values being highest for the context "jar" and lowest for the context "bar". No significant interactions were found for age-by-context, sex-by-context or age-by-sex-context comparisons. Relative formant frequency differences were also examined using Fant's Kn factor, by considering sex-, age- and context-linked patterns. The data also provided some evidence for parallel developmental patterns in the different phonetic contexts of a phrase-final vowel. Furthermore, the results showed that there was some evidence of all three types of the aforementioned patterns in addition to phonetic context-determined changes in K2 factor values. The results reported here, therefore, provide further evidence for age- and sex-linked differences in the patterns of development and maturation of the vocal apparatus.

Phorbol esters and cytokines regulate the expression of the NEMO-related protein, a molecule involved in a NF-kappa B-independent pathway.

The NF-kappaB signaling pathway plays a crucial role in the immune, inflammatory, and apoptotic responses. Recently, we identified the NF-kappaB Essential Modulator (NEMO) as an essential component of this pathway. NEMO is a structural and regulatory subunit of the high molecular kinase complex (IKK) responsible for the phosphorylation of NF-kappaB inhibitors. Data base searching led to the isolation of a cDNA encoding a protein we called NRP (NEMO-related protein), which shows a strong homology to NEMO. Here we show that NRP is present in a novel high molecular weight complex, that contains none of the known members of the IKK complex. Consistently, we could not observe any effect of NRP on NF-kappaB signaling. Nonetheless, we could demonstrate that treatment with phorbol esters induces NRP phosphorylation and decreases its half-life. This phosphorylation event could only be inhibited by K-252a and stauroporin. We also show that de novo expression of NRP can be induced by interferon and tumor necrosis factor alpha and that these two stimuli have a synergistic effect on NRP expression. In addition, we observed that endogenous NRP is associated with the Golgi apparatus. Analogous to NEMO, we find that NRP is associated in a complex with two kinases, suggesting that NRP could play a similar role in another signaling pathway.

Raf induces NF-kappaB by membrane shuttle kinase MEKK1, a signaling pathway critical for transformation.

NF-kappaB is regulated by inhibitor proteins (IkappaBs), which retain NF-kappaB in the cytoplasm. Signal-induced phosphorylation by the IkappaB-kinase complex containing the IkappaB-kinases 1 and 2 (IKK-1/2 or IKK-alpha/beta) and subsequent degradation of the IkappaB proteins are prerequisites for NF-kappaB activation. Many signals induce NF-kappaB, one of them being oncogenic Raf kinase. We investigated whether NF-kappaB induction is critical for Raf-mediated transformation. Here, we demonstrate that inhibition of NF-kappaB interferes with transformation by the Raf-oncogene, and we characterized the mechanism of NF-kappaB induction by activated Raf kinase and the tumor promoter phorbol 12-myristate 13-acetate (PMA). NF-kappaB activation by PMA and Raf critically depends on the IkappaB-kinase complex, most notably on IKK-2. A major signaling pathway induced by Raf is the mitogenic cytoplasmic kinase cascade. However, different inhibitors of this cascade do not affect PMA- and Raf-mediated NF-kappaB activation. Raf does not phosphorylate the IkappaB-kinase proteins directly. Raf rather synergizes with another membrane shuttle kinase MEKK1, and Raf-mediated activation of NF-kappaB is blocked by a dominant negative form of MEKK1. These results suggest that Raf induction of NF-kappaB is relayed by MEKK1, but not by the classical mitogenic cytoplasmic kinase cascade.